Sample records for specific brain functions

  1. EEG classification of emotions using emotion-specific brain functional network.

    PubMed

    Gonuguntla, V; Shafiq, G; Wang, Y; Veluvolu, K C

    2015-08-01

    The brain functional network perspective forms the basis to relate mechanisms of brain functions. This work analyzes the network mechanisms related to human emotion based on synchronization measure - phase-locking value in EEG to formulate the emotion specific brain functional network. Based on network dissimilarities between emotion and rest tasks, most reactive channel pairs and the reactive band corresponding to emotions are identified. With the identified most reactive pairs, the subject-specific functional network is formed. The identified subject-specific and emotion-specific dynamic network pattern show significant synchrony variation in line with the experiment protocol. The same network pattern are then employed for classification of emotions. With the study conducted on the 4 subjects, an average classification accuracy of 62 % was obtained with the proposed technique.

  2. Meta-analysis of functional brain imaging in specific phobia.

    PubMed

    Ipser, Jonathan C; Singh, Leesha; Stein, Dan J

    2013-07-01

    Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  3. 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.

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

    PubMed

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

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

  5. Electro-acupuncture at different acupoints modulating the relative specific brain functional network

    NASA Astrophysics Data System (ADS)

    Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

    2010-11-01

    Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

  6. Functional specificity in the human brain: A window into the functional architecture of the mind

    PubMed Central

    Kanwisher, Nancy

    2010-01-01

    Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain—from the phrenologists to Broca to Chomsky and Fodor—have jousted with the proponents of distributed cognitive and neural processing—from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person’s thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally. PMID:20484679

  7. Functional specificity for high-level linguistic processing in the human brain.

    PubMed

    Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

    2011-09-27

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

  8. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  9. Thermodynamic laws apply to brain function.

    PubMed

    Salerian, Alen J

    2010-02-01

    Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

  10. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

    PubMed

    Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

    2017-08-01

    Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

  11. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    PubMed

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  12. Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

    PubMed Central

    Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T

    1996-01-01

    The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926

  13. Non-verbal emotion communication training induces specific changes in brain function and structure

    PubMed Central

    Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

    2013-01-01

    The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure. PMID:24146641

  14. Non-verbal emotion communication training induces specific changes in brain function and structure.

    PubMed

    Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

    2013-01-01

    The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

  15. Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

    PubMed

    Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

    2015-07-16

    Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

  16. IMAGING OF BRAIN FUNCTION BASED ON THE ANALYSIS OF FUNCTIONAL CONNECTIVITY - IMAGING ANALYSIS OF BRAIN FUNCTION BY FMRI AFTER ACUPUNCTURE AT LR3 IN HEALTHY INDIVIDUALS.

    PubMed

    Zheng, Yu; Wang, Yuying; Lan, Yujun; Qu, Xiaodong; Lin, Kelin; Zhang, Jiping; Qu, Shanshan; Wang, Yanjie; Tang, Chunzhi; Huang, Yong

    2016-01-01

    This Study observed the relevant brain areas activated by acupuncture at the Taichong acupoint (LR3) and analyzed the functional connectivity among brain areas using resting state functional magnetic resonance imaging (fMRI) to explore the acupoint specificity of the Taichong acupoint. A total of 45 healthy subjects were randomly divided into the Taichong (LR3) group, sham acupuncture group and sham acupoint group. Subjects received resting state fMRI before acupuncture, after true (sham) acupuncture in each group. Analysis of changes in connectivity among the brain areas was performed using the brain functional connectivity method. The right cerebrum temporal lobe was selected as the seed point to analyze the functional connectivity. It had a functional connectivity with right cerebrum superior frontal gyrus, limbic lobe cingulate gyrus and left cerebrum inferior temporal gyrus (BA 37), inferior parietal lobule compared by before vs. after acupuncture at LR3, and right cerebrum sub-lobar insula and left cerebrum middle frontal gyrus, medial frontal gyrus compared by true vs. sham acupuncture at LR3, and right cerebrum occipital lobe cuneus, occipital lobe sub-gyral, parietal lobe precuneus and left cerebellum anterior lobe culmen by acupuncture at LR3 vs. sham acupoint. Acupuncture at LR3 mainly specifically activated the brain functional network that participates in visual function, associative function, and emotion cognition, which are similar to the features on LR3 in tradition Chinese medicine. These brain areas constituted a neural network structure with specific functions that had specific reference values for the interpretation of the acupoint specificity of the Taichong acupoint.

  17. 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.

  18. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    PubMed

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

  19. Functional Brain Imaging

    PubMed Central

    2006-01-01

    Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies. Sample sizes of at least 20 patients (≥ 10 with condition being reviewed). English-language studies. Human studies. Any age. Studying at least one of the following: fMRI, PET, MRS, or MEG. Functional brain imaging modality must be compared with a clearly defined reference standard. Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. Summary of Findings There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of

  20. Brain foods: the effects of nutrients on brain function

    PubMed Central

    Gómez-Pinilla, Fernando

    2009-01-01

    It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness. PMID:18568016

  1. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

  2. Brain Structure-function Couplings (FY11)

    DTIC Science & Technology

    2012-01-01

    influence time-evolving models of global brain function and dynamic changes in cognitive performance. Both structural and functional connections change on...Artifact Resistant Measure to Detect Cognitive EEG Activity During Locomotion. Journal of NeuroEngineering and Rehabilitation, submitted. 10...Specifically, identifying the communication between brain regions that occurs during tasks may provide information regarding the cognitive processes involved in

  3. Co-localisation of abnormal brain structure and function in specific language impairment.

    PubMed

    Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

    2012-03-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity.

    PubMed

    Northoff, Georg

    2016-01-01

    What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events.

  5. Generality and specificity in cognitive aging: a volumetric brain analysis.

    PubMed

    Staff, Roger T; Murray, Alison D; Deary, Ian J; Whalley, Lawrence J

    2006-05-01

    To investigate whether, in old age, brain volume differences are associated with age-related change in general mental ability and/or specific cognitive abilities. The authors investigate the association between brain volumes and current cognitive function in a well-characterized sample of healthy old people (aged 79-80) whose intelligence was recorded at age 11. This allowed estimation of intellectual change over the life span. After accounting for childhood intelligence, associations were found between specific cognitive measures and brain volumes. An association was also found between volumes and the general intelligence factor g. After removing the influence of g from each of the specific cognitive measures, no remaining significant associations were found between brain volumes and the specific part of each test. Generalized cognitive aging is associated with brain volume differences, but there is no evidence in this sample that specific components of cognitive aging are associated with differences in brain volume.

  6. Functional expression of SGLTs in rat brain.

    PubMed

    Yu, Amy S; Hirayama, Bruce A; Timbol, Gerald; Liu, Jie; Basarah, Ernest; Kepe, Vladimir; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Wright, Ernest M; Barrio, Jorge R

    2010-12-01

    This work provides evidence of previously unrecognized uptake of glucose via sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The current understanding of functional glucose utilization in brain is largely based on studies using positron emission tomography (PET) with the glucose tracer 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG). However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose accumulation measured by 2-FDG omits the role of SGLTs. We designed and synthesized two high-affinity tracers: one, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-D-glucose (4-FDG), is transported by both SGLTs and GLUTs and will pass through the blood brain barrier (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of uptake by functional SGLTs in brain slices with a comparable result from in vitro 4-FDG autoradiography. Immunohistochemical assays showed that uptake was consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography showed that SGLTs in these areas are functionally active in the normal in vivo brain. The results establish that SGLTs are a normal part of the physiology of specific areas of the brain, including hippocampus, amygdala, hypothalamus, and cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease.

  7. Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI.

    PubMed

    Li, Zhengjun; Vidorreta, Marta; Katchmar, Natalie; Alsop, David C; Wolf, Daniel H; Detre, John A

    2018-06-01

    Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. The effects of vitamin D on brain development and adult brain function.

    PubMed

    Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

    2011-12-05

    A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells.

    PubMed

    Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

    2012-08-15

    Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 μM and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Age-and Brain Region-Specific Differences in Mitochondrial ...

    EPA Pesticide Factsheets

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  11. Advantages in functional imaging of the brain.

    PubMed

    Mier, Walter; Mier, Daniela

    2015-01-01

    As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

  12. Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

    PubMed Central

    Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

    2016-01-01

    Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and

  13. Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain.

    PubMed

    Yamashita, Wataru; Takahashi, Masanori; Kikkawa, Takako; Gotoh, Hitoshi; Osumi, Noriko; Ono, Katsuhiko; Nomura, Tadashi

    2018-04-16

    The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures. © 2018. Published by The Company of Biologists Ltd.

  14. Search for Patterns of Functional Specificity in the Brain: A Nonparametric Hierarchical Bayesian Model for Group fMRI Data

    PubMed Central

    Sridharan, Ramesh; Vul, Edward; Hsieh, Po-Jang; Kanwisher, Nancy; Golland, Polina

    2012-01-01

    Functional MRI studies have uncovered a number of brain areas that demonstrate highly specific functional patterns. In the case of visual object recognition, small, focal regions have been characterized with selectivity for visual categories such as human faces. In this paper, we develop an algorithm that automatically learns patterns of functional specificity from fMRI data in a group of subjects. The method does not require spatial alignment of functional images from different subjects. The algorithm is based on a generative model that comprises two main layers. At the lower level, we express the functional brain response to each stimulus as a binary activation variable. At the next level, we define a prior over sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to learn the patterns of functional specificity shared across the group, which we call functional systems, and estimate the number of these systems. Inference based on our model enables automatic discovery and characterization of dominant and consistent functional systems. We apply the method to data from a visual fMRI study comprised of 69 distinct stimulus images. The discovered system activation profiles correspond to selectivity for a number of image categories such as faces, bodies, and scenes. Among systems found by our method, we identify new areas that are deactivated by face stimuli. In empirical comparisons with perviously proposed exploratory methods, our results appear superior in capturing the structure in the space of visual categories of stimuli. PMID:21884803

  15. The function of neurocognitive networks. Comment on “Understanding brain networks and brain organization” by Pessoa

    NASA Astrophysics Data System (ADS)

    Bressler, Steven L.

    2014-09-01

    Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition.

  16. Functional MRI registration with tissue-specific patch-based functional correlation tensors.

    PubMed

    Zhou, Yujia; Zhang, Han; Zhang, Lichi; Cao, Xiaohuan; Yang, Ru; Feng, Qianjin; Yap, Pew-Thian; Shen, Dinggang

    2018-06-01

    Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) rely on accurate intersubject registration of functional areas. This is typically achieved through registration using high-resolution structural images with more spatial details and better tissue contrast. However, accumulating evidence has suggested that such strategy cannot align functional regions well because functional areas are not necessarily consistent with anatomical structures. To alleviate this problem, a number of registration algorithms based directly on rs-fMRI data have been developed, most of which utilize functional connectivity (FC) features for registration. However, most of these methods usually extract functional features only from the thin and highly curved cortical grey matter (GM), posing great challenges to accurate estimation of whole-brain deformation fields. In this article, we demonstrate that additional useful functional features can also be extracted from the whole brain, not restricted to the GM, particularly the white-matter (WM), for improving the overall functional registration. Specifically, we quantify local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals using tissue-specific patch-based functional correlation tensors (ts-PFCTs) in both GM and WM. Functional registration is then performed by integrating the features from different tissues using the multi-channel large deformation diffeomorphic metric mapping (mLDDMM) algorithm. Experimental results show that our method achieves superior functional registration performance, compared with conventional registration methods. © 2018 Wiley Periodicals, Inc.

  17. Robust Transient Dynamics and Brain Functions

    PubMed Central

    Rabinovich, Mikhail I.; Varona, Pablo

    2011-01-01

    In the last few decades several concepts of dynamical systems theory (DST) have guided psychologists, cognitive scientists, and neuroscientists to rethink about sensory motor behavior and embodied cognition. A critical step in the progress of DST application to the brain (supported by modern methods of brain imaging and multi-electrode recording techniques) has been the transfer of its initial success in motor behavior to mental function, i.e., perception, emotion, and cognition. Open questions from research in genetics, ecology, brain sciences, etc., have changed DST itself and lead to the discovery of a new dynamical phenomenon, i.e., reproducible and robust transients that are at the same time sensitive to informational signals. The goal of this review is to describe a new mathematical framework – heteroclinic sequential dynamics – to understand self-organized activity in the brain that can explain certain aspects of robust itinerant behavior. Specifically, we discuss a hierarchy of coarse-grain models of mental dynamics in the form of kinetic equations of modes. These modes compete for resources at three levels: (i) within the same modality, (ii) among different modalities from the same family (like perception), and (iii) among modalities from different families (like emotion and cognition). The analysis of the conditions for robustness, i.e., the structural stability of transient (sequential) dynamics, give us the possibility to explain phenomena like the finite capacity of our sequential working memory – a vital cognitive function –, and to find specific dynamical signatures – different kinds of instabilities – of several brain functions and mental diseases. PMID:21716642

  18. Improving Functional MRI Registration Using Whole-Brain Functional Correlation Tensors.

    PubMed

    Zhou, Yujia; Yap, Pew-Thian; Zhang, Han; Zhang, Lichi; Feng, Qianjin; Shen, Dinggang

    2017-09-01

    Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) largely rely on the accurate inter-subject registration of functional areas. This is typically achieved through registration of the corresponding T1-weighted MR images with more structural details. However, accumulating evidence has suggested that such strategy cannot well-align functional regions which are not necessarily confined by the anatomical boundaries defined by the T1-weighted MR images. To mitigate this problem, various registration algorithms based directly on rs-fMRI data have been developed, most of which have utilized functional connectivity (FC) as features for registration. However, most of the FC-based registration methods usually extract the functional features only from the thin and highly curved cortical grey matter (GM), posing a great challenge in accurately estimating the whole-brain deformation field. In this paper, we demonstrate that the additional useful functional features can be extracted from brain regions beyond the GM, particularly, white-matter (WM) based on rs-fMRI, for improving the overall functional registration. Specifically, we quantify the local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals, modeled by functional correlation tensors (FCTs), in both GM and WM. Functional registration is then performed based on multiple components of the whole-brain FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM) algorithm. Experimental results show that our proposed method achieves superior functional registration performance, compared with other conventional registration methods.

  19. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    PubMed Central

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  20. Functional organization of the transcriptome in human brain

    PubMed Central

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

    2009-01-01

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

  1. Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

    PubMed

    de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

    2018-01-01

    Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain

  2. Neuronal survival in the brain: neuron type-specific mechanisms.

    PubMed

    Pfisterer, Ulrich; Khodosevich, Konstantin

    2017-03-02

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  3. Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury

    PubMed Central

    Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.

    2011-01-01

    Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974

  4. Neuropsychological functioning and brain structure in schizophrenia.

    PubMed

    Crespo-Facorro, Benedicto; Barbadillo, Laura; Pelayo-Terán, José Maria; Rodríguez-Sánchez, José Manuel

    2007-08-01

    Cognitive deficits are core features of schizophrenia that are already evident at early phases of the illness. The study of specific relationships between cognition and brain structure might provide valuable clues about neural basis of schizophrenia and its phenomenology. The aim of this article was to review the most consistent findings of the studies exploring the relationships between cognitive deficits and brain anomalies in schizophrenia. Besides several important methodological shortcomings to bear in mind before drawing any consistent conclusion from the revised literature, we have attempted to systematically summarize these findings. Thus, this review has revealed that whole brain volume tends to positively correlate with a range of cognitive domains in healthy volunteers and female patients. An association between prefrontal morphological characteristics and general inability to control behaviour seems to be present in schizophrenia patients. Parahippocampal volume is related to semantic cognitive functions. Thalamic anomalies have been associated with executive deficits specifically in patients. Available evidence on the relationship between cognitive functions and cerebellar structure is still contradictory. Nonetheless, a larger cerebellum appears to be associated with higher IQ in controls and in female patients. Enlarged ventricles, including lateral and third ventricles, are associated with deficits in attention, executive and premorbid cognitive functioning in patients. Several of these reported findings seem to be counterintuitive according to neural basis of cognitive functioning drawn from animal, lesion, and functional imaging investigations. Therefore, there is still a great need for more methodologically stringent investigations that would help in the advance of our understanding of the cognition/brain structure relationships in schizophrenia.

  5. Localization and functional analysis of the insect-specific RabX4 in the brain of Bombyx mori.

    PubMed

    Uno, Tomohide; Furutani, Masayuki; Sakamoto, Katsuhiko; Uno, Yuichi; Kanamaru, Kengo; Mizoguchi, Akira; Hiragaki, Susumu; Takeda, Makio

    2017-09-01

    Rab proteins are small monomeric GTPases/GTP-binding proteins, which form the largest branch of the Ras superfamily. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they function as regulators of distinct steps in membrane trafficking. RabX4 is an insect-specific Rab protein that has no close homolog in vertebrates. There is little information about insect-specific Rab proteins. RabX4 was expressed in Escherichia coli and subsequently purified. Antibodies against Bombyx mori RabX4 were produced in rabbits for western immunoblotting and immunohistochemistry. Western blotting of neural tissues revealed a single band, at approximately 26 kD. RabX4-like immunohistochemical reactivity was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum in the brain. Further immunohistochemical analysis revealed that RabX4 colocalized with Rab6 and bombyxin in the corpus allatum, a neuronal organ that secretes neuropeptides synthesized in the brain into the hemolymph. RabX4 expression in the frontal ganglion, part of the insect stomatogastric nervous system that is found in most insect orders, was restricted to two neurons on the outer region and did not colocalize with allatotropin or Rab6. Furthermore, RNA interference of RabX4 decreased bombyxin expression levels in the brain. These findings suggest that RabX4 is involved in the neurosecretion of a secretory organ in Bombyx mori. © 2017 Wiley Periodicals, Inc.

  6. Population differences in brain morphology: Need for population specific brain template.

    PubMed

    Rao, Naren P; Jeelani, Haris; Achalia, Rashmin; Achalia, Garima; Jacob, Arpitha; Bharath, Rose Dawn; Varambally, Shivarama; Venkatasubramanian, Ganesan; K Yalavarthy, Phaneendra

    2017-07-30

    Brain templates provide a standard anatomical platform for population based morphometric assessments. Typically, standard brain templates for such assessments are created using Caucasian brains, which may not be ideal to analyze brains from other ethnicities. To effectively demonstrate this, we compared brain morphometric differences between T1 weighted structural MRI images of 27 healthy Indian and Caucasian subjects of similar age and same sex ratio. Furthermore, a population specific brain template was created from MRI images of healthy Indian subjects and compared with standard Montreal Neurological Institute (MNI-152) template. We also examined the accuracy of registration of by acquiring a different T1 weighted MRI data set and registering them to newly created Indian template and MNI-152 template. The statistical analysis indicates significant difference in global brain measures and regional brain structures of Indian and Caucasian subjects. Specifically, the global brain measurements of the Indian brain template were smaller than that of the MNI template. Also, Indian brain images were better realigned to the newly created template than to the MNI-152 template. The notable variations in Indian and Caucasian brains convey the need to build a population specific Indian brain template and atlas. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Age-related functional brain changes in young children.

    PubMed

    Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

    2017-07-15

    Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Concerted and mosaic evolution of functional modules in songbird brains

    PubMed Central

    DeVoogd, Timothy J.

    2017-01-01

    Vertebrate brains differ in overall size, composition and functional capacities, but the evolutionary processes linking these traits are unclear. Two leading models offer opposing views: the concerted model ascribes major dimensions of covariation in brain structures to developmental events, whereas the mosaic model relates divergent structures to functional capabilities. The models are often cast as incompatible, but they must be unified to explain how adaptive changes in brain structure arise from pre-existing architectures and developmental mechanisms. Here we show that variation in the sizes of discrete neural systems in songbirds, a species-rich group exhibiting diverse behavioural and ecological specializations, supports major elements of both models. In accordance with the concerted model, most variation in nucleus volumes is shared across functional domains and allometry is related to developmental sequence. Per the mosaic model, residual variation in nucleus volumes is correlated within functional systems and predicts specific behavioural capabilities. These comparisons indicate that oscine brains evolved primarily as a coordinated whole but also experienced significant, independent modifications to dedicated systems from specific selection pressures. Finally, patterns of covariation between species and brain areas hint at underlying developmental mechanisms. PMID:28490627

  9. Evolving knowledge of sex differences in brain structure, function, and chemistry.

    PubMed

    Cosgrove, Kelly P; Mazure, Carolyn M; Staley, Julie K

    2007-10-15

    Clinical and epidemiologic evidence demonstrates sex differences in the prevalence and course of various psychiatric disorders. Understanding sex-specific brain differences in healthy individuals is a critical first step toward understanding sex-specific expression of psychiatric disorders. Here, we evaluate evidence on sex differences in brain structure, chemistry, and function using imaging methodologies, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy individuals. MEDLINE searches of English-language literature (1980-November 2006) using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry, and neurotransmission were performed to extract relevant sources. The literature suggests that while there are many similarities in brain structure, function, and neurotransmission in healthy men and women, there are important differences that distinguish the male from the female brain. Overall, brain volume is greater in men than women; yet, when controlling for total volume, women have a higher percentage of gray matter and men a higher percentage of white matter. Regional volume differences are less consistent. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains are neurochemically distinct. Insight into the etiology of sex differences in the normal living human brain provides an important foundation to delineate the pathophysiological mechanisms underlying sex differences in neuropsychiatric disorders and to guide the development of sex-specific treatments for these devastating brain disorders.

  10. Diffeomorphic functional brain surface alignment: Functional demons.

    PubMed

    Nenning, Karl-Heinz; Liu, Hesheng; Ghosh, Satrajit S; Sabuncu, Mert R; Schwartz, Ernst; Langs, Georg

    2017-08-01

    Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Functional brain networks reconstruction using group sparsity-regularized learning.

    PubMed

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

    2018-06-01

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

  12. Sugar for the brain: the role of glucose in physiological and pathological brain function

    PubMed Central

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

    2013-01-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

  13. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    PubMed Central

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR

  14. Sex-specific associations of testosterone with prefrontal-hippocampal development and executive function.

    PubMed

    Nguyen, Tuong-Vi; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Ducharme, Simon; McCracken, James T

    2017-02-01

    Testosterone is thought to play a crucial role in mediating sexual differentiation of brain structures. Examinations of the cognitive effects of testosterone have also shown beneficial and potentially sex-specific effects on executive function and mnemonic processes. Yet these findings remain limited by an incomplete understanding of the critical timing and brain regions most affected by testosterone, the lack of documented links between testosterone-related structural brain changes and cognition, and the difficulty in distinguishing the effects of testosterone from those of related sex steroids such as of estradiol and dehydroepiandrosterone (DHEA). Here we examined associations between testosterone, cortico-hippocampal structural covariance, executive function (Behavior Rating Inventory of Executive Function) and verbal memory (California Verbal Learning Test-Children's Version), in a longitudinal sample of typically developing children and adolescents 6-22 yo, controlling for the effects of estradiol, DHEA, pubertal stage, collection time, age, handedness, and total brain volume. We found prefrontal-hippocampal covariance to vary as a function of testosterone levels, but only in boys. Boys also showed a specific association between positive prefrontal-hippocampal covariance (as seen at higher testosterone levels) and lower performance on specific components of executive function (monitoring the action process and flexibly shifting between actions). We also found the association between testosterone and a specific aspect of executive function (monitoring) to be significantly mediated by prefrontal-hippocampal structural covariance. There were no significant associations between testosterone-related cortico-hippocampal covariance and verbal memory. Taken together, these findings highlight the developmental importance of testosterone in supporting sexual differentiation of the brain and sex-specific executive function. Copyright © 2016 Elsevier Ltd. All rights

  15. Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

    PubMed Central

    Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

    2013-01-01

    Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

  16. Functional brain imaging: an evidence-based analysis.

    PubMed

    2006-01-01

    Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS'), and retrospective studies.Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).English-language studies.Human studies.Any age.STUDYING AT LEAST ONE OF THE FOLLOWING: fMRI, PET, MRS, or MEG.Functional brain imaging modality must be compared with a clearly defined reference standard.MUST REPORT AT LEAST ONE OF THE FOLLOWING OUTCOMES: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-(18)F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers

  17. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    PubMed

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Laminar fMRI and computational theories of brain function.

    PubMed

    Stephan, K E; Petzschner, F H; Kasper, L; Bayer, J; Wellstein, K V; Stefanics, G; Pruessmann, K P; Heinzle, J

    2017-11-02

    Recently developed methods for functional MRI at the resolution of cortical layers (laminar fMRI) offer a novel window into neurophysiological mechanisms of cortical activity. Beyond physiology, laminar fMRI also offers an unprecedented opportunity to test influential theories of brain function. Specifically, hierarchical Bayesian theories of brain function, such as predictive coding, assign specific computational roles to different cortical layers. Combined with computational models, laminar fMRI offers a unique opportunity to test these proposals noninvasively in humans. This review provides a brief overview of predictive coding and related hierarchical Bayesian theories, summarises their predictions with regard to layered cortical computations, examines how these predictions could be tested by laminar fMRI, and considers methodological challenges. We conclude by discussing the potential of laminar fMRI for clinically useful computational assays of layer-specific information processing. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Describing functional diversity of brain regions and brain networks

    PubMed Central

    Anderson, Michael L.; Kinnison, Josh; Pessoa, Luiz

    2013-01-01

    Despite the general acceptance that functional specialization plays an important role in brain function, there is little consensus about its extent in the brain. We sought to advance the understanding of this question by employing a data-driven approach that capitalizes on the existence of large databases of neuroimaging data. We quantified the diversity of activation in brain regions as a way to characterize the degree of functional specialization. To do so, brain activations were classified in terms of task domains, such as vision, attention, and language, which determined a region’s functional fingerprint. We found that the degree of diversity varied considerably across the brain. We also quantified novel properties of regions and of networks that inform our understanding of several task-positive and task-negative networks described in the literature, including defining functional fingerprints for entire networks and measuring their functional assortativity, namely the degree to which they are composed of regions with similar functional fingerprints. Our results demonstrate that some brain networks exhibit strong assortativity, whereas other networks consist of relatively heterogeneous parts. In sum, rather than characterizing the contributions of individual brain regions using task-based functional attributions, we instead quantified their dispositional tendencies, and related those to each region’s affiliative properties in both task-positive and task-negative contexts. PMID:23396162

  20. Variability in functional brain networks predicts expertise during action observation.

    PubMed

    Amoruso, Lucía; Ibáñez, Agustín; Fonseca, Bruno; Gadea, Sebastián; Sedeño, Lucas; Sigman, Mariano; García, Adolfo M; Fraiman, Ricardo; Fraiman, Daniel

    2017-02-01

    Observing an action performed by another individual activates, in the observer, similar circuits as those involved in the actual execution of that action. This activation is modulated by prior experience; indeed, sustained training in a particular motor domain leads to structural and functional changes in critical brain areas. Here, we capitalized on a novel graph-theory approach to electroencephalographic data (Fraiman et al., 2016) to test whether variability in functional brain networks implicated in Tango observation can discriminate between groups differing in their level of expertise. We found that experts and beginners significantly differed in the functional organization of task-relevant networks. Specifically, networks in expert Tango dancers exhibited less variability and a more robust functional architecture. Notably, these expertise-dependent effects were captured within networks derived from electrophysiological brain activity recorded in a very short time window (2s). In brief, variability in the organization of task-related networks seems to be a highly sensitive indicator of long-lasting training effects. This finding opens new methodological and theoretical windows to explore the impact of domain-specific expertise on brain plasticity, while highlighting variability as a fruitful measure in neuroimaging research. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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

  2. Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain.

    PubMed

    Khalifa, Abdel Rahman M; Abdel-Rahman, Engy A; Mahmoud, Ali M; Ali, Mohamed H; Noureldin, Maha; Saber, Saber H; Mohsen, Mahmoud; Ali, Sameh S

    2017-03-01

    Sex-specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well-established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration and higher reserve capacity. This was associated with lower H 2 O 2 production in female cardiac and brain tissues. Using transmission electron microscopy, we found that the number of female cardiac mitochondria is moderately greater (117 ± 3%, P  = 0.049, N  = 4) than male's, which increased significantly for cortical mitochondria (134 ± 4%, P  = 0.001, N  = 4). However, male's cardiac mitochondria exhibited fragmented, circular, and smaller mitochondria relative to female's mitochondria, while no morphologic sex-dependent differences were observed in cortical mitochondria. No sex differences were detected in Nox2 and Nox4 proteins or O 2 -consuming/H 2 O 2 -producing activities in brain homogenate or synaptosomes. However, a strong trend of increased EPR-detected NOX superoxide in male synaptosomes hinted at higher superoxide dismutase activity in female brains, which was confirmed by two independent protocols. We also provide direct evidence that respiring mitochondria generally produce an order-of-magnitude lower reactive oxygen species (ROS) proportions than currently estimated. Our results indicate that sex differences in mitochondrial biogenesis, bioenergetics, and morphology may start at young age and that sex-dependent SOD capacity may be responsible for differences in ROS homeostasis in heart and brain. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological

  3. Korea Brain Initiative: Integration and Control of Brain Functions.

    PubMed

    Jeong, Sung-Jin; Lee, Haejin; Hur, Eun-Mi; Choe, Youngshik; Koo, Ja Wook; Rah, Jong-Cheol; Lee, Kea Joo; Lim, Hyun-Ho; Sun, Woong; Moon, Cheil; Kim, Kyungjin

    2016-11-02

    This article introduces the history and the long-term goals of the Korea Brain Initiative, which is centered on deciphering the brain functions and mechanisms that mediate the integration and control of brain functions that underlie decision-making. The goal of this initiative is the mapping of a functional connectome with searchable, multi-dimensional, and information-integrated features. The project also includes the development of novel technologies and neuro-tools for integrated brain mapping. Beyond the scientific goals this grand endeavor will ultimately have socioeconomic ramifications that not only facilitate global collaboration in the neuroscience community, but also develop various brain science-related industrial and medical innovations. Copyright © 2016. Published by Elsevier Inc.

  4. Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics.

    PubMed

    Thompson, John W; Sorum, Alexander W; Hsieh-Wilson, Linda C

    2018-06-23

    The dynamic posttranslational modification O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease. Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins. However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy. Given the sheer number of O-GlcNAc sites, methods are greatly needed to identify promising sites and prioritize them for time- and resource-intensive functional studies. Revealing sites that are dynamically altered by different stimuli or disease states will likely to go a long way in this regard. Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome, and for determining their stoichiometry in vivo. We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites. These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloging of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins. By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.

  5. Hemispheric asymmetry of electroencephalography-based functional brain networks.

    PubMed

    Jalili, Mahdi

    2014-11-12

    Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

  6. Brain responses in 4-month-old infants are already language specific.

    PubMed

    Friederici, Angela D; Friedrich, Manuela; Christophe, Anne

    2007-07-17

    Language is the most important faculty that distinguishes humans from other animals. Infants learn their native language fast and effortlessly during the first years of life, as a function of the linguistic input in their environment. Behavioral studies reported the discrimination of melodic contours [1] and stress patterns [2, 3] in 1-4-month-olds. Behavioral [4, 5] and brain measures [6-8] have shown language-independent discrimination of phonetic contrasts at that age. Language-specific discrimination, however, has been reported for phonetic contrasts only for 6-12-month-olds [9-12]. Here we demonstrate language-specific discrimination of stress patterns in 4-month-old German and French infants by using electrophysiological brain measures. We compare the processing of disyllabic words differing in their rhythmic structure, mimicking German words being stressed on the first syllable, e.g., pápa/daddy[13], and French ones being stressed on the second syllable, e.g., papá/daddy. Event-related brain potentials reveal that experience with German and French differentially affects the brain responses of 4-month-old infants, with each language group displaying a processing advantage for the rhythmic structure typical in its native language. These data indicate language-specific neural representations of word forms in the infant brain as early as 4 months of age.

  7. An Isozyme-specific Redox Switch in Human Brain Glycogen Phosphorylase Modulates Its Allosteric Activation by AMP.

    PubMed

    Mathieu, Cécile; Duval, Romain; Cocaign, Angélique; Petit, Emile; Bui, Linh-Chi; Haddad, Iman; Vinh, Joelle; Etchebest, Catherine; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-11-11

    Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP). In this study, we show that the activity of human bGP is redox-regulated through the formation of a disulfide bond involving a highly reactive cysteine unique to the bGP isozyme. We found that this disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. A review on functional and structural brain connectivity in numerical cognition

    PubMed Central

    Moeller, Korbinian; Willmes, Klaus; Klein, Elise

    2015-01-01

    Only recently has the complex anatomo-functional system underlying numerical cognition become accessible to evaluation in the living brain. We identified 27 studies investigating brain connectivity in numerical cognition. Despite considerable heterogeneity regarding methodological approaches, populations investigated, and assessment procedures implemented, the results provided largely converging evidence regarding the underlying brain connectivity involved in numerical cognition. Analyses of both functional/effective as well as structural connectivity have consistently corroborated the assumption that numerical cognition is subserved by a fronto-parietal network including (intra)parietal as well as (pre)frontal cortex sites. Evaluation of structural connectivity has indicated the involvement of fronto-parietal association fibers encompassing the superior longitudinal fasciculus dorsally and the external capsule/extreme capsule system ventrally. Additionally, commissural fibers seem to connect the bilateral intraparietal sulci when number magnitude information is processed. Finally, the identification of projection fibers such as the superior corona radiata indicates connections between cortex and basal ganglia as well as the thalamus in numerical cognition. Studies on functional/effective connectivity further indicated a specific role of the hippocampus. These specifications of brain connectivity augment the triple-code model of number processing and calculation with respect to how gray matter areas associated with specific number-related representations may work together. PMID:26029075

  9. DHA Effects in Brain Development and Function

    PubMed Central

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-01

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

  10. DHA Effects in Brain Development and Function.

    PubMed

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-04

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.

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

    PubMed

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

    2013-07-01

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

  12. The Role of Sleep in Emotional Brain Function

    PubMed Central

    Goldstein, Andrea N.; Walker, Matthew P.

    2014-01-01

    Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

  13. Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

    PubMed Central

    Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

  14. Magnetic Resonance, Functional (fMRI) -- Brain

    MedlinePlus

    ... thought, speech, movement and sensation, which is called brain mapping. help assess the effects of stroke, trauma, or degenerative disease (such as Alzheimer's) on brain function. monitor the growth and function of brain ...

  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

  16. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

    PubMed Central

    Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

    2014-01-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  17. Whole-brain functional connectivity identification of functional dyspepsia.

    PubMed

    Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie

    2013-01-01

    Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

  18. Executive Functions and Social Skills in Survivors of Pediatric Brain Tumor

    PubMed Central

    Wolfe, Kelly R.; Walsh, Karin S.; Reynolds, Nina C.; Mitchell, Frances; Reddy, Alyssa T.; Paltin, Iris; Madan-Swain, Avi

    2012-01-01

    Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper and pencil measures of social skills and real world executive skills. Social functioning was related to a specific aspect of executive functions, i.e., the survivors’ variability in response time, such that inconsistent responding was associated with better parent-report and survivor-report social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed. PMID:22420326

  19. Cytokine Signaling Modulates Blood-Brain Barrier Function

    PubMed Central

    Pan, Weihong; Stone, Kirsten P.; Hsuchou, Hung; Manda, Vamshi K.; Zhang, Yan; Kastin, Abba J.

    2014-01-01

    The blood-brain barrier (BBB) provides a vast interface for cytokines to affect CNS function. The BBB is a target for therapeutic intervention. It is essential, therefore, to understand how cytokines interact with each other at the level of the BBB and how secondary signals modulate CNS functions beyond the BBB. The interactions between cytokines and lipids, however, have not been fully addressed at the level of the BBB. Here, we summarize current understanding of the localization of cytokine receptors and transporters in specific membrane microdomains, particularly lipid rafts, on the luminal (apical) surface of the microvascular endothelial cells composing the BBB. We then illustrate the clinical context of cytokine effects on the BBB by neuroendocrine regulation and amplification of inflammatory signals. Two unusual aspects discussed are signaling crosstalk by different classes of cytokines and genetic regulation of drug efflux transporters. We also introduce a novel area of focus on how cytokines may act through nuclear hormone receptors to modulate efflux transporters and other targets. A specific example discussed is the ATP-binding cassette transporter-1 (ABCA-1) that regulates lipid metabolism. Overall, cytokine signaling at the level of the BBB is a crucial feature of the dynamic regulation that can rapidly change BBB function and affect brain health and disease. PMID:21834767

  20. Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

    PubMed

    Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

    2017-07-13

    Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

    DOE PAGES

    Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.; ...

    2016-05-09

    Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

  2. Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

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

    Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.

    Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

  3. Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

    NASA Astrophysics Data System (ADS)

    Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

    1999-05-01

    The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

  4. Temporal Dynamics Assessment of Spatial Overlap Pattern of Functional Brain Networks Reveals Novel Functional Architecture of Cerebral Cortex.

    PubMed

    Jiang, Xi; Li, Xiang; Lv, Jinglei; Zhao, Shijie; Zhang, Shu; Zhang, Wei; Zhang, Tuo; Han, Junwei; Guo, Lei; Liu, Tianming

    2018-06-01

    Various studies in the brain mapping field have demonstrated that there exist multiple concurrent functional networks that are spatially overlapped and interacting with each other during specific task performance to jointly realize the total brain function. Assessing such spatial overlap patterns of functional networks (SOPFNs) based on functional magnetic resonance imaging (fMRI) has thus received increasing interest for brain function studies. However, there are still two crucial issues to be addressed. First, the SOPFNs are assessed over the entire fMRI scan assuming the temporal stationarity, while possibly time-dependent dynamics of the SOPFNs is not sufficiently explored. Second, the SOPFNs are assessed within individual subjects, while group-wise consistency of the SOPFNs is largely unknown. To address the two issues, we propose a novel computational framework of group-wise sparse representation of whole-brain fMRI temporal segments to assess the temporal dynamic spatial patterns of SOPFNs that are consistent across different subjects. Experimental results based on the recently publicly released Human Connectome Project grayordinate task fMRI data demonstrate that meaningful SOPFNs exhibiting dynamic spatial patterns across different time periods are effectively and robustly identified based on the reconstructed concurrent functional networks via the proposed framework. Specifically, those SOPFNs locate significantly more on gyral regions than on sulcal regions across different time periods. These results reveal novel functional architecture of cortical gyri and sulci. Moreover, these results help better understand functional dynamics mechanisms of cerebral cortex in the future.

  5. From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

    PubMed

    Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

    2016-11-03

    Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Brain noise is task dependent and region specific.

    PubMed

    Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

    2010-11-01

    The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

  7. Frequency specific brain networks in Parkinson's disease and comorbid depression.

    PubMed

    Qian, Long; Zhang, Yi; Zheng, Li; Fu, Xuemei; Liu, Weiguo; Shang, Yuqing; Zhang, Yaoyu; Xu, Yuanyuan; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

    2017-02-01

    The topological organization underlying the human brain was extensively investigated using resting-state functional magnetic resonance imaging, focusing on a low frequency of signal oscillation from 0.01 to 0.1 Hz. However, the frequency specificities with regard to the topological properties of the brain networks have not been fully revealed. In this study, a novel complementary ensemble empirical mode decomposition (CEEMD) method was used to separate the fMRI time series into five characteristic oscillations with distinct frequencies. Then, the small world properties of brain networks were analyzed for each of these five oscillations in patients (n = 67) with depressed Parkinson's disease (DPD, n = 20) , non-depressed Parkinson's disease (NDPD, n = 47) and healthy controls (HC, n = 46). Compared with HC, the results showed decreased network efficiency in characteristic oscillations from 0.05 to 0.12 Hz and from 0.02 to 0.05 Hz for the DPD and NDPD patients, respectively. Furthermore, compared with HC, the most significant inter-group difference across five brain oscillations was found in the basal ganglia (0.01 to 0.05 Hz) and paralimbic-limbic network (0.02 to 0.22 Hz) for the DPD patients, and in the visual cortex (0.02 to 0.05 Hz) for the NDPD patients. Compared with NDPD, the DPD patients showed reduced efficiency of nodes in the basal ganglia network (0.01 to 0.05 Hz). Our results demonstrated that DPD is characterized by a disrupted topological organization in large-scale brain functional networks. Moreover, the CEEMD analysis suggested a prominent dissociation in the topological organization of brain networks between DPD and NDPD in both space and frequency domains. Our findings indicated that these characteristic oscillatory activities in different functional circuits may contribute to distinct motor and non-motor components of clinical impairments in Parkinson's disease.

  8. Videogame training strategy-induced change in brain function during a complex visuomotor task.

    PubMed

    Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

    2012-07-01

    Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Stimulating at the right time: phase-specific deep brain stimulation.

    PubMed

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  10. Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI

    PubMed Central

    Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen

    2012-01-01

    The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI. PMID:22952990

  11. Decoding lifespan changes of the human brain using resting-state functional connectivity MRI.

    PubMed

    Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen

    2012-01-01

    The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8-79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' "brain ages" from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI.

  12. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    PubMed Central

    Kleinridders, André; Ferris, Heather A.; Cai, Weikang

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

  13. [Brain function recovery after prolonged posttraumatic coma].

    PubMed

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  14. Cerebral energy metabolism and the brain's functional network architecture: an integrative review.

    PubMed

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-09-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's 'functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks.

  15. Microglia function in brain tumors.

    PubMed

    Watters, Jyoti J; Schartner, Jill M; Badie, Behnam

    2005-08-01

    Microglia play an important role in inflammatory diseases of the central nervous system (CNS). These cells have also been identified in brain neoplasms; however, as of yet their function largely remains unclear. More recent studies designed to characterize further tumor-associated microglia suggest that the immune effector function of these cells may be suppressed in CNS tumors. Furthermore, microglia and macrophages can secrete various cytokines and growth factors that may contribute to the successful immune evasion, growth, and invasion of brain neoplasms. A better understanding of microglia and macrophage function is essential for the development of immune-based treatment strategies against malignant brain tumors. (c) 2005 Wiley-Liss, Inc.

  16. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    PubMed

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  17. How the brain attunes to sentence processing: Relating behavior, structure, and function

    PubMed Central

    Fengler, Anja; Meyer, Lars; Friederici, Angela D.

    2016-01-01

    Unlike other aspects of language comprehension, the ability to process complex sentences develops rather late in life. Brain maturation as well as verbal working memory (vWM) expansion have been discussed as possible reasons. To determine the factors contributing to this functional development, we assessed three aspects in different age-groups (5–6 years, 7–8 years, and adults): first, functional brain activity during the processing of increasingly complex sentences; second, brain structure in language-related ROIs; and third, the behavioral comprehension performance on complex sentences and the performance on an independent vWM test. At the whole-brain level, brain functional data revealed a qualitatively similar neural network in children and adults including the left pars opercularis (PO), the left inferior parietal lobe together with the posterior superior temporal gyrus (IPL/pSTG), the supplementary motor area, and the cerebellum. While functional activation of the language-related ROIs PO and IPL/pSTG predicted sentence comprehension performance for all age-groups, only adults showed a functional selectivity in these brain regions with increased activation for more complex sentences. The attunement of both the PO and IPL/pSTG toward a functional selectivity for complex sentences is predicted by region-specific gray matter reduction while that of the IPL/pSTG is additionally predicted by vWM span. Thus, both structural brain maturation and vWM expansion provide the basis for the emergence of functional selectivity in language-related brain regions leading to more efficient sentence processing during development. PMID:26777477

  18. Altered resting brain function and structure in professional badminton players.

    PubMed

    Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

    2012-01-01

    Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

  19. Altered Resting Brain Function and Structure in Professional Badminton Players

    PubMed Central

    Di, Xin; Zhu, Senhua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan

    2012-01-01

    Abstract Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

  20. 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.

  1. Brain Connectivity and Functional Recovery in Patients With Ischemic Stroke.

    PubMed

    Almeida, Sara Regina Meira; Vicentini, Jessica; Bonilha, Leonardo; De Campos, Brunno M; Casseb, Raphael F; Min, Li Li

    2017-01-01

    Brain mapping studies have demonstrated that functional poststroke brain reorganization is associated with recovery of motor function. Nonetheless, the specific mechanisms associated with functional reorganization leading to motor recovery are still partly unknown. In this study, we performed a cross-sectional evaluation of poststroke subjects with the following goals: (1) To assess intra- and interhemispheric functional brain activation patterns associated with motor function in poststroke patients with variable degrees of recovery; (2) to investigate the involvement of other nonmotor functional networks in relationship with recovery. We studied 59 individuals: 13 patients with function Rankin > 1 and Barthel < 100; 19 patients with preserved function with Rankin 0-1 and Barthel = 100; and 27 healthy controls. All subjects underwent structural and functional magnetic resonance imaging (3T Philips Achieva, Holland) using the same protocol (TR = 2 seconds, TE = 30 ms, FOV = 240 × 240 × 117, slice = 39). Resting state functional connectivity was used by in-house software, based on SPM12. Among patients with and without preserved function, the functional connectivity between the primary motor region (M1) and the contralateral hemisphere was increased compared with controls. Nonetheless, only patients with decreased function exhibited decreased functional connectivity between executive control, sensorimotor and visuospatial networks. Functional recovery after stroke is associated with preserved functional connectivity of motor to nonmotor networks. Copyright © 2016 by the American Society of Neuroimaging.

  2. Identification of alterations associated with age in the clustering structure of functional brain networks.

    PubMed

    Guzman, Grover E C; Sato, Joao R; Vidal, Maciel C; Fujita, Andre

    2018-01-01

    Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

  3. Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction

    PubMed Central

    Wang, Danhong; Buckner, Randy L.

    2014-01-01

    The human brain demonstrates functional specialization, including strong hemispheric asymmetries. Here specialization was explored using fMRI by examining the degree to which brain networks preferentially interact with ipsilateral as opposed to contralateral networks. Preferential within-hemisphere interaction was prominent in the heteromodal association cortices and minimal in the sensorimotor cortices. The frontoparietal control network exhibited strong within-hemisphere interactions but with distinct patterns in each hemisphere. The frontoparietal control network preferentially coupled to the default network and language-related regions in the left hemisphere but to attention networks in the right hemisphere. This arrangement may facilitate control of processing functions that are lateralized. Moreover, the regions most linked to asymmetric specialization also display the highest degree of evolutionary cortical expansion. Functional specialization that emphasizes processing within a hemisphere may allow the expanded hominin brain to minimize between-hemisphere connectivity and distribute domain-specific processing functions. PMID:25209275

  4. Her versus his migraine: multiple sex differences in brain function and structure.

    PubMed

    Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

    2012-08-01

    Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

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

    PubMed Central

    2016-01-01

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

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

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

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

  7. Stimulating at the right time: phase-specific deep brain stimulation

    PubMed Central

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    Abstract See Moll and Engel (doi:10.1093/aww308) for a scientific commentary on this article. Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson’s disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient’s tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. PMID:28007997

  8. Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

    PubMed Central

    Vawter, Marquis P; Evans, Simon; Choudary, Prabhakara; Tomita, Hiroaki; Meador-Woodruff, Jim; Molnar, Margherita; Li, Jun; Lopez, Juan F; Myers, Rick; Cox, David; Watson, Stanley J; Akil, Huda; Jones, Edward G; Bunney, William E

    2011-01-01

    Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex- chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences. PMID:14583743

  9. The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.

    PubMed

    Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro

    2014-11-01

    Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen. © 2014 by the Society for Experimental Biology and Medicine.

  10. Dynamic reconfiguration of human brain functional networks through neurofeedback.

    PubMed

    Haller, Sven; Kopel, Rotem; Jhooti, Permi; Haas, Tanja; Scharnowski, Frank; Lovblad, Karl-Olof; Scheffler, Klaus; Van De Ville, Dimitri

    2013-11-01

    Recent fMRI studies demonstrated that functional connectivity is altered following cognitive tasks (e.g., learning) or due to various neurological disorders. We tested whether real-time fMRI-based neurofeedback can be a tool to voluntarily reconfigure brain network interactions. To disentangle learning-related from regulation-related effects, we first trained participants to voluntarily regulate activity in the auditory cortex (training phase) and subsequently asked participants to exert learned voluntary self-regulation in the absence of feedback (transfer phase without learning). Using independent component analysis (ICA), we found network reconfigurations (increases in functional network connectivity) during the neurofeedback training phase between the auditory target region and (1) the auditory pathway; (2) visual regions related to visual feedback processing; (3) insula related to introspection and self-regulation and (4) working memory and high-level visual attention areas related to cognitive effort. Interestingly, the auditory target region was identified as the hub of the reconfigured functional networks without a-priori assumptions. During the transfer phase, we again found specific functional connectivity reconfiguration between auditory and attention network confirming the specific effect of self-regulation on functional connectivity. Functional connectivity to working memory related networks was no longer altered consistent with the absent demand on working memory. We demonstrate that neurofeedback learning is mediated by widespread changes in functional connectivity. In contrast, applying learned self-regulation involves more limited and specific network changes in an auditory setup intended as a model for tinnitus. Hence, neurofeedback training might be used to promote recovery from neurological disorders that are linked to abnormal patterns of brain connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Brain structure and function correlates of cognitive subtypes in schizophrenia.

    PubMed

    Geisler, Daniel; Walton, Esther; Naylor, Melissa; Roessner, Veit; Lim, Kelvin O; Charles Schulz, S; Gollub, Randy L; Calhoun, Vince D; Sponheim, Scott R; Ehrlich, Stefan

    2015-10-30

    Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Whole Brain Functional Connectivity Pattern Homogeneity Mapping.

    PubMed

    Wang, Lijie; Xu, Jinping; Wang, Chao; Wang, Jiaojian

    2018-01-01

    Mounting studies have demonstrated that brain functions are determined by its external functional connectivity patterns. However, how to characterize the voxel-wise similarity of whole brain functional connectivity pattern is still largely unknown. In this study, we introduced a new method called functional connectivity homogeneity (FcHo) to delineate the voxel-wise similarity of whole brain functional connectivity patterns. FcHo was defined by measuring the whole brain functional connectivity patterns similarity of a given voxel with its nearest 26 neighbors using Kendall's coefficient concordance (KCC). The robustness of this method was tested in four independent datasets selected from a large repository of MRI. Furthermore, FcHo mapping results were further validated using the nearest 18 and six neighbors and intra-subject reproducibility with each subject scanned two times. We also compared FcHo distribution patterns with local regional homogeneity (ReHo) to identify the similarity and differences of the two methods. Finally, FcHo method was used to identify the differences of whole brain functional connectivity patterns between professional Chinese chess players and novices to test its application. FcHo mapping consistently revealed that the high FcHo was mainly distributed in association cortex including parietal lobe, frontal lobe, occipital lobe and default mode network (DMN) related areas, whereas the low FcHo was mainly found in unimodal cortex including primary visual cortex, sensorimotor cortex, paracentral lobule and supplementary motor area. These results were further supported by analyses of the nearest 18 and six neighbors and intra-subject similarity. Moreover, FcHo showed both similar and different whole brain distribution patterns compared to ReHo. Finally, we demonstrated that FcHo can effectively identify the whole brain functional connectivity pattern differences between professional Chinese chess players and novices. Our findings indicated

  13. 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.

  14. 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

  15. Integration of fMRI, NIROT and ERP for studies of human brain function.

    PubMed

    Gore, John C; Horovitz, Silvina G; Cannistraci, Christopher J; Skudlarski, Pavel

    2006-05-01

    Different methods of assessing human brain function possess specific advantages and disadvantages compared to others, but it is believed that combining different approaches will provide greater information than can be obtained from each alone. For example, functional magnetic resonance imaging (fMRI) has good spatial resolution but poor temporal resolution, whereas the converse is true for electrophysiological recordings (event-related potentials or ERPs). In this review of recent work, we highlight a novel approach to combining these modalities in a manner designed to increase information on the origins and locations of the generators of specific ERPs and the relationship between fMRI and ERP signals. Near infrared imaging techniques have also been studied as alternatives to fMRI and can be readily integrated with simultaneous electrophysiological recordings. Each of these modalities may in principle be also used in so-called steady-state acquisitions in which the correlational structure of signals from the brain may be analyzed to provide new insights into brain function.

  16. [Dextrals and sinistrals (right-handers and left-handers): specificity of interhemispheric brain asymmetry and EEG coherence parameters].

    PubMed

    Zhavoronkova, L A

    2007-01-01

    Data of literature about morphological, functional and biochemical specificity of the brain interhemispheric asymmetry of healthy right-handers and left-handers and about peculiarity of dynamics of cerebral pathology in patients with different individual asymmetry profiles are presented at the present article. Results of our investigation by using coherence parameters of electroencephalogram (EEG) in healthy right-handers and left-handers in state of rest, during functional tests and sleeping and in patients with different forms of the brain organic damage were analyzed too. EEG coherence analysis revealed the reciprocal changing of alpha-beta and theta-delta spectral bands in right-handers whilein left-handers synchronous changing of all EEG spectral bands were observed. Data about regional-frequent specificity of EEG coherence, peculiarity of EEG asymmetry in right-handers and left-handers, aslo about specificity of EEG spectral band genesis and point of view about a role of the brain regulator systems in forming of interhemispheric asymmetry in different functional states allowed to propose the conception about principle of interhermispheric brain asymmetry formation in left-handers and left-handers. Following this conception in dextrals elements of concurrent (summary-reciprocal) cooperation are predominant at the character of interhemispheric and cortical-subcortical interaction while in sinistrals a principle of concordance (supplementary) is preferable. These peculiarities the brain organization determine, from the first side, the quicker revovery of functions damaged after cranio-cerebral trauma in left-handers in comparison right-handers and from the other side - they determine the forming of the more expressed pathology in the remote terms after exposure the low dose of radiation.

  17. The development of Human Functional Brain Networks

    PubMed Central

    Power, Jonathan D; Fair, Damien A; Schlaggar, Bradley L

    2010-01-01

    Recent advances in MRI technology have enabled precise measurements of correlated activity throughout the brain, leading to the first comprehensive descriptions of functional brain networks in humans. This article reviews the growing literature on the development of functional networks, from infancy through adolescence, as measured by resting state functional connectivity MRI. We note several limitations of traditional approaches to describing brain networks, and describe a powerful framework for analyzing networks, called graph theory. We argue that characterization of the development of brain systems (e.g. the default mode network) should be comprehensive, considering not only relationships within a given system, but also how these relationships are situated within wider network contexts. We note that, despite substantial reorganization of functional connectivity, several large-scale network properties appear to be preserved across development, suggesting that functional brain networks, even in children, are organized in manners similar to other complex systems. PMID:20826306

  18. Functional brain connectivity when cooperation fails.

    PubMed

    Balconi, Michela; Vanutelli, Maria Elide; Gatti, Laura

    2018-06-01

    Functional connectivity during cooperative actions is an important topic in social neuroscience that has yet to be answered. Here, we examined the effects of administration of (fictitious) negative social feedback in relation to cooperative capabilities. Cognitive performance and neural activation underlying the execution of joint actions was recorded with functional near-infrared spectroscopy (fNIRS) on prefrontal regions during a task where pairs of participants received negative feedback after their joint action. Performance (error rates (ERs) and response times (RTs)) and intra- and inter-brain connectivity indices were computed, along with the ConIndex (inter-brain/intra-brain connectivity). Finally, correlational measures were considered to assess the relation between these different measures. Results showed that the negative feedback was able to modulate participants' responses for both behavioral and neural components. Cognitive performance was decreased after the feedback. Moreover, decreased inter-brain connectivity and increased intra-brain connectivity was induced by the feedback, whereas the cooperative task pre-feedback condition was able to increase the brain-to-brain coupling, mainly localized within the dorsolateral prefrontal cortex (DLPFC). Finally, the presence of significant correlations between RTs and inter-brain connectivity revealed that ineffective joint action produces the worst cognitive performance and a more 'individual strategy' for brain activity, limiting the inter-brain connectivity. The present study provides a significant contribution to the identification of patterns of intra- and inter-brain functional connectivity when negative social reinforcement is provided in relation to cooperative actions. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS.

    PubMed

    Shi, Ran; Guo, Ying

    2016-12-01

    Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).

  20. Functional Specificity of the Visual Word Form Area: General Activation for Words and Symbols but Specific Network Activation for Words

    ERIC Educational Resources Information Center

    Reinke, Karen; Fernandes, Myra; Schwindt, Graeme; O'Craven, Kathleen; Grady, Cheryl L.

    2008-01-01

    The functional specificity of the brain region known as the Visual Word Form Area (VWFA) was examined using fMRI. We explored whether this area serves a general role in processing symbolic stimuli, rather than being selective for the processing of words. Brain activity was measured during a visual 1-back task to English words, meaningful symbols…

  1. 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.

  2. [Three-dimensional reconstruction of functional brain images].

    PubMed

    Inoue, M; Shoji, K; Kojima, H; Hirano, S; Naito, Y; Honjo, I

    1999-08-01

    We consider PET (positron emission tomography) measurement with SPM (Statistical Parametric Mapping) analysis to be one of the most useful methods to identify activated areas of the brain involved in language processing. SPM is an effective analytical method that detects markedly activated areas over the whole brain. However, with the conventional presentations of these functional brain images, such as horizontal slices, three directional projection, or brain surface coloring, makes understanding and interpreting the positional relationships among various brain areas difficult. Therefore, we developed three-dimensionally reconstructed images from these functional brain images to improve the interpretation. The subjects were 12 normal volunteers. The following three types of images were constructed: 1) routine images by SPM, 2) three-dimensional static images, and 3) three-dimensional dynamic images, after PET images were analyzed by SPM during daily dialog listening. The creation of images of both the three-dimensional static and dynamic types employed the volume rendering method by VTK (The Visualization Toolkit). Since the functional brain images did not include original brain images, we synthesized SPM and MRI brain images by self-made C++ programs. The three-dimensional dynamic images were made by sequencing static images with available software. Images of both the three-dimensional static and dynamic types were processed by a personal computer system. Our newly created images showed clearer positional relationships among activated brain areas compared to the conventional method. To date, functional brain images have been employed in fields such as neurology or neurosurgery, however, these images may be useful even in the field of otorhinolaryngology, to assess hearing and speech. Exact three-dimensional images based on functional brain images are important for exact and intuitive interpretation, and may lead to new developments in brain science. Currently, the

  3. Similarity in functional brain architecture between rest and specific task modes: A model of genetic and environmental contributions to episodic memory.

    PubMed

    Petrican, Raluca; Levine, Brian T

    2018-06-21

    The ability to keep a mental record of specific past events, dubbed episodic memory (EM), is key to lifespan adaptation. Nonetheless, the neural mechanisms underlying its typical inter-individual variability remain poorly understood. To address this issue, we tested whether individual differences in EM could be predicted from levels of functional brain re-organization between rest and task modes relevant to the transformation of perceptual information into mental representations (relational processing, meaning extraction, online maintenance versus updating of bound perceptual features). To probe the trait specificity of our model, we included three additional core mental functions, processing speed, abstract reasoning, and cognitive control. Finally, we investigated the extent to which our proposed model reflected genetic versus environmental contributions to EM variability. Hypotheses were tested by applying graph theoretical analysis and structural equation modeling to resting state and task fMRI data from two samples of participants in the Human Connectome Project (Sample 1: N = 338 unrelated individuals; Sample 2: N = 268 monozygotic vs. dizygotic twins [134 same-sex pairs]). Levels of functional brain reorganization between rest and the scrutinized task modes, particularly relational processing and online maintenance of bound perceptual features, contributed substantially to variations in both EM and abstract reasoning (but not in cognitive control or processing speed) among the younger adults in our sample, implying a substantial neurofunctional overlap, at least during this life stage. Similarity in functional organization between rest and each of the scrutinized task modes drew on distinguishable neural resources and showed differential susceptibility to genetic versus environmental influences. Our results suggest that variability on complex traits, such as EM, is supported by neural mechanisms comprising multiple components, each reflecting a

  4. Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

    PubMed Central

    Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

    2014-01-01

    Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

  5. Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training.

    PubMed

    Levine, Brian; Schweizer, Tom A; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T; Manly, Tom; Robertson, Ian H

    2011-01-01

    Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits.

  6. Her versus his migraine: multiple sex differences in brain function and structure

    PubMed Central

    Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

    2012-01-01

    Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414

  7. Brain and Behavioral Assessment of Executive Functions for Self-Regulating Levels of Language in Reading Brain.

    PubMed

    Berninger, Virginia W; Richards, Todd L; Abbott, Robert D

    2017-11-01

    This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language-subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning

  8. Analyzing the association between functional connectivity of the brain and intellectual performance

    PubMed Central

    Pamplona, Gustavo S. P.; Santos Neto, Gérson S.; Rosset, Sara R. E.; Rogers, Baxter P.; Salmon, Carlos E. G.

    2015-01-01

    Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus, and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding. PMID:25713528

  9. The power of using functional fMRI on small rodents to study brain pharmacology and disease

    PubMed Central

    Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie

    2015-01-01

    Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological

  10. Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.

    PubMed

    Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Macià, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

    2015-03-01

    Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

    PubMed Central

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

  12. Branched-chain amino acids and brain function.

    PubMed

    Fernstrom, John D

    2005-06-01

    Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

  13. Brain dynamics in ASD during movie-watching show idiosyncratic functional integration and segregation.

    PubMed

    Bolton, Thomas A W; Jochaut, Delphine; Giraud, Anne-Lise; Van De Ville, Dimitri

    2018-06-01

    To refine our understanding of autism spectrum disorders (ASD), studies of the brain in dynamic, multimodal and ecological experimental settings are required. One way to achieve this is to compare the neural responses of ASD and typically developing (TD) individuals when viewing a naturalistic movie, but the temporal complexity of the stimulus hampers this task, and the presence of intrinsic functional connectivity (FC) may overshadow movie-driven fluctuations. Here, we detected inter-subject functional correlation (ISFC) transients to disentangle movie-induced functional changes from underlying resting-state activity while probing FC dynamically. When considering the number of significant ISFC excursions triggered by the movie across the brain, connections between remote functional modules were more heterogeneously engaged in the ASD population. Dynamically tracking the temporal profiles of those ISFC changes and tying them to specific movie subparts, this idiosyncrasy in ASD responses was then shown to involve functional integration and segregation mechanisms such as response inhibition, background suppression, or multisensory integration, while low-level visual processing was spared. Through the application of a new framework for the study of dynamic experimental paradigms, our results reveal a temporally localized idiosyncrasy in ASD responses, specific to short-lived episodes of long-range functional interplays. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  14. Functional brain correlates of heterosexual paedophilia.

    PubMed

    Schiffer, Boris; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Kruger, Tillmann H C

    2008-05-15

    Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing.

  15. BEND3 is involved in the human-specific repression of calreticulin: Implication for the evolution of higher brain functions in human.

    PubMed

    Aghajanirefah, A; Nguyen, L N; Ohadi, M

    2016-01-15

    Recent emerging evidence indicates that changes in gene expression levels are linked to human evolution. We have previously reported a human-specific nucleotide in the promoter sequence of the calreticulin (CALR) gene at position -220C, which is the site of action of valproic acid. Reversion of this nucleotide to the ancestral A-allele has been detected in patients with degrees of deficit in higher brain cognitive functions. This mutation has since been reported in the 1000 genomes database at an approximate frequency of <0.0004 in humans (rs138452745). In the study reported here, we present update on the status of rs138452745 across evolution, based on the Ensembl and NCBI databases. The DNA pulldown assay was also used to identify the proteins binding to the C- and A-alleles, using two cell lines, SK-N-BE and HeLa. Consistent with our previous findings, the C-allele is human-specific, and the A-allele is the rule across all other species (N=38). This nucleotide resides in a block of 12-nucleotides that is strictly conserved across evolution. The DNA pulldown experiments revealed that in both SK-N-BE and HeLa cells, the transcription repressor BEN domain containing 3 (BEND3) binds to the human-specific C-allele, whereas the nuclear factor I (NFI) family members, NF1A, B, C, and X, specifically bind to the ancestral A-allele. This binding pattern is consistent with a previously reported decreased promoter activity of the C-allele vs. the A-allele. We propose that there is a link between binding of BEND3 to the CALR rs138452745 C-allele and removal of NFI binding site from this nucleotide, and the evolution of human-specific higher brain functions. To our knowledge, CALR rs138452745 is the first instance of enormous nucleotide conservation across evolution, except in the human species. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Encoding and Retrieving Faces and Places: Distinguishing Process- and Stimulus-Specific Differences in Brain Activity

    ERIC Educational Resources Information Center

    Prince, Steven E.; Dennis, Nancy A.; Cabeza, Roberto

    2009-01-01

    Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little…

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

    PubMed

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

    2015-03-01

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

  18. Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

    PubMed

    Lee, Dongha; Pae, Chongwon; Lee, Jong Doo; Park, Eun Sook; Cho, Sung-Rae; Um, Min-Hee; Lee, Seung-Koo; Oh, Maeng-Keun; Park, Hae-Jeong

    2017-10-01

    Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals

  19. Brain volume and cognitive function in patients with revascularized coronary artery disease.

    PubMed

    Ottens, Thomas H; Hendrikse, Jeroen; Nathoe, Hendrik M; Biessels, Geert Jan; van Dijk, Diederik

    2017-03-01

    The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore investigated brain volume and cognitive function in patients with revascularized coronary artery disease (CAD), and controls without CAD. Brain MRI scans and cognitive tests from patients with CAD were compared with data from control subjects without CAD. Cognitive performance was assessed with the Rey Auditory Verbal Learning (short term memory) and Trailmaking (divided attention) tests. Multivariable regression analysis was used to study associations between CAD, brain volume and cognitive function. A total of 102 patients with CAD and 48 control subjects were included. Level of education and age were comparable between the groups. Compared with controls, patients with CAD had smaller total brain volume (expressed as fraction of intracranial volume) [%ICV, mean (SD), 0.78 (0.03) vs 0.80 (0.02), P=0.001] and larger volume of non-ventricular cerebrospinal fluid [%ICV, median (IQR) 0.19 (0.18 to 0.21) vs 0.18 (0.17 to 0.20), P=0.001]. Patients in the CAD group had poorer cognitive function [mean (SD) Z-score -0.16 (0.72) vs 0.41 (0.69), P<0.01]. Multivariable regression showed that CAD, higher age, lower level of education and greater cerebrospinal fluid volume were independent predictors of poorer cognitive function. CAD patients had a smaller total brain volume and poorer cognitive function than controls. Greater volume of cerebrospinal fluid was an independent predictor of poorer cognitive function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Glycolysis-mediated control of blood-brain barrier development and function.

    PubMed

    Salmina, Alla B; Kuvacheva, Natalia V; Morgun, Andrey V; Komleva, Yulia K; Pozhilenkova, Elena A; Lopatina, Olga L; Gorina, Yana V; Taranushenko, Tatyana E; Petrova, Lyudmila L

    2015-07-01

    The blood-brain barrier (BBB) consists of differentiated cells integrating in one ensemble to control transport processes between the central nervous system (CNS) and peripheral blood. Molecular organization of BBB affects the extracellular content and cell metabolism in the CNS. Developmental aspects of BBB attract much attention in recent years, and barriergenesis is currently recognized as a very important and complex mechanism of CNS development and maturation. Metabolic control of angiogenesis/barriergenesis may be provided by glucose utilization within the neurovascular unit (NVU). The role of glycolysis in the brain has been reconsidered recently, and it is recognized now not only as a process active in hypoxic conditions, but also as a mechanism affecting signal transduction, synaptic activity, and brain development. There is growing evidence that glycolysis-derived metabolites, particularly, lactate, affect barriergenesis and functioning of BBB. In the brain, lactate produced in astrocytes or endothelial cells can be transported to the extracellular space via monocarboxylate transporters (MCTs), and may act on the adjoining cells via specific lactate receptors. Astrocytes are one of the major sources of lactate production in the brain and significantly contribute to the regulation of BBB development and functioning. Active glycolysis in astrocytes is required for effective support of neuronal activity and angiogenesis, while endothelial cells regulate bioavailability of lactate for brain cells adjusting its bidirectional transport through the BBB. In this article, we review the current knowledge with regard to energy production in endothelial and astroglial cells within the NVU. In addition, we describe lactate-driven mechanisms and action of alternative products of glucose metabolism affecting BBB structural and functional integrity in developing and mature brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A Factor Analysis of Functional Independence and Functional Assessment Measure Scores Among Focal and Diffuse Brain Injury Patients: The Importance of Bifactor Models.

    PubMed

    Gunn, Sarah; Burgess, Gerald H; Maltby, John

    2018-04-30

    To explore the factor structure of the UK Functional Independence Measure and Functional Assessment Measure (FIM+FAM) among focal and diffuse acquired brain injury patients. Criterion standard. A National Health Service acute acquired brain injury inpatient rehabilitation hospital. Referred sample of N=447 adults admitted for inpatient treatment following an acquired brain injury significant enough to justify intensive inpatient neurorehabilitation INTERVENTION: Not applicable. Functional Independence Measure and Functional Assessment Measure. Exploratory factor analysis suggested a 2-factor structure to FIM+FAM scores, among both focal-proximate and diffuse-proximate acquired brain injury aetiologies. Confirmatory factor analysis suggested a 3-factor bifactor structure presented the best fit of the FIM+FAM score data across both aetiologies. However, across both analyses, a convergence was found towards a general factor, demonstrated by high correlations between factors in the exploratory factor analysis, and by a general factor explaining the majority of the variance in scores on confirmatory factor analysis. Our findings suggested that although factors describing specific functional domains can be derived from FIM+FAM item scores, there is a convergence towards a single factor describing overall functioning. This single factor informs the specific group factors (eg, motor, psychosocial, and communication function) after brain injury. Further research into the comparative value of the general and group factors as evaluative/prognostic measures is indicated. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

    PubMed Central

    Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.

    2012-01-01

    Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469

  3. Rehabilitation of Executive Functioning in Patients with Frontal Lobe Brain Damage with Goal Management Training

    PubMed Central

    Levine, Brian; Schweizer, Tom A.; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T.; Manly, Tom; Robertson, Ian H.

    2011-01-01

    Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits. PMID:21369362

  4. Sex steroid hormones and brain function: PET imaging as a tool for research.

    PubMed

    Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

    2018-02-01

    Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for

  5. Structural and functional rich club organization of the brain in children and adults.

    PubMed

    Grayson, David S; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G Costa; Stevens, Corinne; Nigg, Joel T; Fair, Damien A

    2014-01-01

    Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.

  6. Split My Brain: A Case Study of Seizure Disorder and Brain Function

    ERIC Educational Resources Information Center

    Omarzu, Julia

    2004-01-01

    This case involves a couple deciding whether or not their son should undergo brain surgery to treat a severe seizure disorder. In examining this dilemma, students apply knowledge of brain anatomy and function. They also learn about brain scanning techniques and discuss the plasticity of the brain.

  7. Site specificity of adrenalectomy-induced brain growth.

    PubMed

    Thomas, T L; Devenport, L D

    1988-12-01

    Infant, juvenile, and adult brain growth is modulated by corticosterone. This study was designed to determine whether such modulation is confined to certain specific brain areas, and if the pattern of growth revealed is consistent across strains of rats. Young female Sprague-Dawley-derived rats were either adrenalectomized (ADX) or sham-operated (Sham) and allowed to mature 45 days before they were sacrificed for histological analysis. Fore brain sections were taken at several planes for display by projection microscope. Of the 21 sites examined, ADX exerted its greatest effect upon neocortical tissue and myelinated fiber tracts. The only other brain region affected was thalamus, which exhibited a significant widening as a result of ADX. In contrast, archicortical structures were notably unaffected by ADX. Neither the hippocampus, measured from a variety of planes, nor nuclei in the septal area were subject to increased growth by ADX. This general portrayal of ADX's site specificity held across strains of rats. However, there were local differences. Within the neopallium, the frontal region underwent the greatest thickening in one strain, while the occipital area was most strongly affected in the other. Parietal cortex was equally responsive in both strains. The pattern of sensitive vs insensitive sites bore a resemblance to the pattern of increased growth brought about by environmental enrichment as well as the fore brain distribution of Type 2 corticosterone receptors.

  8. Resting-state functional brain connectivity: lessons from functional near-infrared spectroscopy.

    PubMed

    Niu, Haijing; He, Yong

    2014-04-01

    Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area of interest and is currently attracting considerable attention as a new imaging tool for the study of resting-state brain function. Using variations in hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency spontaneous neural activity, combining the advantages of portability, low-cost, high temporal sampling rate and less physical burden to participants. The temporal synchronization of spontaneous neuronal activity in anatomically separated regions is referred to as resting-state functional connectivity (RSFC). In the past several years, an increasing body of R-fNIRS RSFC studies has led to many important findings about functional integration among local or whole-brain regions by measuring inter-regional temporal synchronization. Here, we summarize recent advances made in the R-fNIRS RSFC methodologies, from the detection of RSFC (e.g., seed-based correlation analysis, independent component analysis, whole-brain correlation analysis, and graph-theoretical topological analysis), to the assessment of RSFC performance (e.g., reliability, repeatability, and validity), to the application of RSFC in studying normal development and brain disorders. The literature reviewed here suggests that RSFC analyses based on R-fNIRS data are valid and reliable for the study of brain function in healthy and diseased populations, thus providing a promising imaging tool for cognitive science and clinics.

  9. Localization of Asymmetric Brain Function in Emotion and Depression

    PubMed Central

    Herrington, John D.; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S.; Banich, Marie T.; Webb, Andrew G.; Miller, Gregory A.

    2011-01-01

    Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used. PMID:20070577

  10. Localization of asymmetric brain function in emotion and depression.

    PubMed

    Herrington, John D; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S; Banich, Marie T; Webb, Andrew G; Miller, Gregory A

    2010-05-01

    Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.

  11. Functional vision in children with perinatal brain damage.

    PubMed

    Alimović, Sonja; Jurić, Nikolina; Bošnjak, Vlatka Mejaški

    2014-09-01

    Many authors have discussed the effects of visual stimulations on visual functions, but there is no research about the effects on using vision in everyday activities (i.e. functional vision). Children with perinatal brain damage can develop cerebral visual impairment with preserved visual functions (e.g. visual acuity, contrast sensitivity) but poor functional vision. Our aim was to discuss the importance of assessing and stimulating functional vision in children with perinatal brain damage. We assessed visual functions (grating visual acuity, contrast sensitivity) and functional vision (the ability of maintaining visual attention and using vision in communication) in 99 children with perinatal brain damage and visual impairment. All children were assessed before and after the visual stimulation program. Our first assessment results showed that children with perinatal brain damage had significantly more problems in functional vision than in basic visual functions. During the visual stimulation program both variables of functional vision and contrast sensitivity improved significantly, while grating acuity improved only in 2.7% of children. We also found that improvement of visual attention significantly correlated to improvement on all other functions describing vision. Therefore, functional vision assessment, especially assessment of visual attention is indispensable in early monitoring of child with perinatal brain damage.

  12. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information

  13. Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

    PubMed

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P

    2012-04-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

  14. Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

    PubMed

    Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang

    2018-06-01

    Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.

  15. Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

    PubMed

    Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas

    2012-08-01

    In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with

  16. Functional salutogenic mechanisms of the brain.

    PubMed

    Smith, Donald F

    2002-01-01

    Neuroscientists are typically interested in the brain in relation to disease, but much could also be learned by studying the brain in relation to health. The brain has processes, functional salutogenic mechanisms, that contribute to health by enabling one's outlook on life to benefit one's health. For example, the belief that things will work out as well as can reasonably be expected is a key aspect of the outlook of people who tend to stay well even when in potentially stressful situations. Believing in God, feeling happy, being mutually in love, and expecting things to change for the better are also outlooks that can be salutogenic. Beliefs need not even be rational or realistic in order for them to be salutogenic, as shown by phenomena such as faith healing and the placebo effect. Thus, the brain responds to stimuli and interprets them, mainly without one's awareness, in ways that can enhance one's well-being. Although little is presently known concerning neuropathways of functional salutogenic mechanisms, further research on relations between salutogenesis and brain function can be expected to provide new strategies for improving health worldwide.

  17. Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain

    PubMed Central

    Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo

    2010-01-01

    Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL

  18. On imputing function to structure from the behavioural effects of brain lesions.

    PubMed

    Young, M P; Hilgetag, C C; Scannell, J W

    2000-01-29

    What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.

  19. Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration.

    PubMed

    Ma, Zhiwei; Perez, Pablo; Ma, Zilu; Liu, Yikang; Hamilton, Christina; Liang, Zhifeng; Zhang, Nanyin

    2018-04-15

    Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole-brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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

  1. White matter lesions relate to tract-specific reductions in functional connectivity.

    PubMed

    Langen, Carolyn D; Zonneveld, Hazel I; White, Tonya; Huizinga, Wyke; Cremers, Lotte G M; de Groot, Marius; Ikram, Mohammad Arfan; Niessen, Wiro J; Vernooij, Meike W

    2017-03-01

    White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Brain and Behavioral Assessment of Executive Functions for Self-Regulating Levels of Language in Reading Brain

    PubMed Central

    Berninger, Virginia W.; Richards, Todd L.; Abbott, Robert D.

    2017-01-01

    This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language—subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning

  3. Functional Geometry Alignment and Localization of Brain Areas.

    PubMed

    Langs, Georg; Golland, Polina; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J

    2010-01-01

    Matching functional brain regions across individuals is a challenging task, largely due to the variability in their location and extent. It is particularly difficult, but highly relevant, for patients with pathologies such as brain tumors, which can cause substantial reorganization of functional systems. In such cases spatial registration based on anatomical data is only of limited value if the goal is to establish correspondences of functional areas among different individuals, or to localize potentially displaced active regions. Rather than rely on spatial alignment, we propose to perform registration in an alternative space whose geometry is governed by the functional interaction patterns in the brain. We first embed each brain into a functional map that reflects connectivity patterns during a fMRI experiment. The resulting functional maps are then registered, and the obtained correspondences are propagated back to the two brains. In application to a language fMRI experiment, our preliminary results suggest that the proposed method yields improved functional correspondences across subjects. This advantage is pronounced for subjects with tumors that affect the language areas and thus cause spatial reorganization of the functional regions.

  4. In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging

    PubMed Central

    LEVINE, BRIAN; FUJIWARA, ESTHER; O’CONNOR, CHARLENE; RICHARD, NADINE; KOVACEVIC, NATASA; MANDIC, MARINA; RESTAGNO, ADRIANA; EASDON, CRAIG; ROBERTSON, IAN H.; GRAHAM, SIMON J.; CHEUNG, GORDON; GAO, FUQIANG; SCHWARTZ, MICHAEL L.; BLACK, SANDRA E.

    2007-01-01

    Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior. PMID:17020478

  5. Functional network organization of the human brain

    PubMed Central

    Power, Jonathan D; Cohen, Alexander L; Nelson, Steven M; Wig, Gagan S; Barnes, Kelly Anne; Church, Jessica A; Vogel, Alecia C; Laumann, Timothy O; Miezin, Fran M; Schlaggar, Bradley L; Petersen, Steven E

    2011-01-01

    Summary Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a “processing” system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex. PMID:22099467

  6. Detecting Brain State Changes via Fiber-Centered Functional Connectivity Analysis

    PubMed Central

    Li, Xiang; Lim, Chulwoo; Li, Kaiming; Guo, Lei; Liu, Tianming

    2013-01-01

    Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been widely used to study structural and functional brain connectivity in recent years. A common assumption used in many previous functional brain connectivity studies is the temporal stationarity. However, accumulating literature evidence has suggested that functional brain connectivity is under temporal dynamic changes in different time scales. In this paper, a novel and intuitive approach is proposed to model and detect dynamic changes of functional brain states based on multimodal fMRI/DTI data. The basic idea is that functional connectivity patterns of all fiber-connected cortical voxels are concatenated into a descriptive functional feature vector to represent the brain’s state, and the temporal change points of brain states are decided by detecting the abrupt changes of the functional vector patterns via the sliding window approach. Our extensive experimental results have shown that meaningful brain state change points can be detected in task-based fMRI/DTI, resting state fMRI/DTI, and natural stimulus fMRI/DTI data sets. Particularly, the detected change points of functional brain states in task-based fMRI corresponded well to the external stimulus paradigm administered to the participating subjects, thus partially validating the proposed brain state change detection approach. The work in this paper provides novel perspective on the dynamic behaviors of functional brain connectivity and offers a starting point for future elucidation of the complex patterns of functional brain interactions and dynamics. PMID:22941508

  7. Construction of population-specific Indian MRI brain template: Morphometric comparison with Chinese and Caucasian templates.

    PubMed

    Bhalerao, Gaurav Vivek; Parlikar, Rujuta; Agrawal, Rimjhim; Shivakumar, Venkataram; Kalmady, Sunil V; Rao, Naren P; Agarwal, Sri Mahavir; Narayanaswamy, Janardhanan C; Reddy, Y C Janardhan; Venkatasubramanian, Ganesan

    2018-06-01

    Spatial normalization of brain MR images is highly dependent on the choice of target brain template. Morphological differences caused by factors like genetic and environmental exposures, generates a necessity to construct population specific brain templates. Brain image analysis performed using brain templates from Caucasian population may not be appropriate for non-Caucasian population. In this study, our objective was to construct an Indian brain template from a large population (N = 157 subjects) and compare the morphometric parameters of this template with that of Chinese-56 and MNI-152 templates. In addition, using an independent MRI data of 15 Indian subjects, we also evaluated the potential registration accuracy differences using these three templates. Indian brain template was constructed using iterative routines as per established procedures. We compared our Indian template with standard MNI-152 template and Chinese template by measuring global brain features. We also examined accuracy of registration by aligning 15 new Indian brains to Indian, Chinese and MNI templates. Furthermore, we supported our measurement protocol with inter-rater and intra-rater reliability analysis. Our results showed that there were significant differences in global brain features of Indian template in comparison with Chinese and MNI brain templates. The results of registration accuracy analysis revealed that fewer deformations are required when Indian brains are registered to Indian template as compared to Chinese and MNI templates. This study concludes that population specific Indian template is likely to be more appropriate for structural and functional image analysis of Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. The brain's default network: anatomy, function, and relevance to disease.

    PubMed

    Buckner, Randy L; Andrews-Hanna, Jessica R; Schacter, Daniel L

    2008-03-01

    Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.

  9. Electroencephalographic imaging of higher brain function

    NASA Technical Reports Server (NTRS)

    Gevins, A.; Smith, M. E.; McEvoy, L. K.; Leong, H.; Le, J.

    1999-01-01

    High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

  10. Functional brain networks for learning predictive statistics.

    PubMed

    Giorgio, Joseph; Karlaftis, Vasilis M; Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew; Kourtzi, Zoe

    2017-08-18

    Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men At A Glance Using ... video games for one week causes changes in brain function. The brain regions affected by violent video ...

  12. Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

    PubMed

    Bartolomeo, Paolo; Thiebaut de Schotten, Michel

    2016-12-01

    Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Brain structure and executive functions in children with cerebral palsy: a systematic review.

    PubMed

    Weierink, Lonneke; Vermeulen, R Jeroen; Boyd, Roslyn N

    2013-05-01

    This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

    PubMed

    Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

    2015-07-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family

  15. Effects of different correlation metrics and preprocessing factors on small-world brain functional networks: a resting-state functional MRI study.

    PubMed

    Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

    2012-01-01

    Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01-0.027 Hz) versus slow-4 (0.027-0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the "best" network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027-0.073 Hz band exhibited greater reliability than those in the 0.01-0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific

  16. Effects of Different Correlation Metrics and Preprocessing Factors on Small-World Brain Functional Networks: A Resting-State Functional MRI Study

    PubMed Central

    Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

    2012-01-01

    Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01–0.027 Hz) versus slow-4 (0.027–0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the “best” network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027–0.073 Hz band exhibited greater reliability than those in the 0.01–0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics

  17. Diagnostic Accuracy, Sensitivity, and Specificity of Executive Function Tests in Moderate Traumatic Brain Injury in Ghana.

    PubMed

    Adjorlolo, Samuel

    2018-06-01

    The sociocultural differences between Western and sub-Saharan African countries make it imperative to standardize neuropsychological tests in the latter. However, Western-normed tests are frequently administered in sub-Saharan Africa because of challenges hampering standardization efforts. Yet a salient topical issue in the cross-cultural neuropsychology literature relates to the utility of Western-normed neuropsychological tests in minority groups, non-Caucasians, and by extension Ghanaians. Consequently, this study investigates the diagnostic accuracy, sensitivity, and specificity of executive function (EF) tests (The Stroop Test, Trail Making Test, and Controlled Oral Word Association Test), and a Revised Quick Cognitive Screening Test (RQCST) in a sample of 50 patients diagnosed with moderate traumatic brain injury and 50 healthy controls in Ghana. The EF test scores showed good diagnostic accuracy, with area under the curve (AUC) values of the Trail Making Test scores ranging from .746 to .902. With respect to the Stroop Test scores, the AUC values ranged from .793 to .898, while Controlled Oral Word Association Test had AUC value of .787. The RQCST scores discriminated between the groups, with AUC values ranging from .674 to .912. The AUC values of composite EF score and a neuropsychological score created from EF and RQCST scores were .936 and. 942, respectively. Additionally, the Stroop Test, Trail Making Test, EF composite score, and RQCST scores showed good to excellent sensitivities and specificities. In general, this study has shown that commonly used EF tests in Western countries have diagnostic accuracy, sensitivity, and specificity when administered in Ghanaian samples. The findings and implications of the study are discussed.

  18. Development of the brain's functional network architecture.

    PubMed

    Vogel, Alecia C; Power, Jonathan D; Petersen, Steven E; Schlaggar, Bradley L

    2010-12-01

    A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.

  19. Development of the Brain's Functional Network Architecture

    PubMed Central

    Power, Jonathan D.; Petersen, Steven E.; Schlaggar, Bradley L.

    2013-01-01

    A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks. PMID:20976563

  20. Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

    PubMed Central

    Rabiller, Gratianne; He, Ji-Wei; Nishijima, Yasuo; Wong, Aaron; Liu, Jialing

    2015-01-01

    Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG) in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV), θ (4–8 Hz, 10 μV), α (8–12 Hz, 20–200 μV), β (12–30 Hz, 5–10 μV), and γ (30–80 Hz, low amplitude). Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy. PMID:26516838

  1. Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface.

    PubMed

    Young, Brittany M; Nigogosyan, Zack; Walton, Léo M; Song, Jie; Nair, Veena A; Grogan, Scott W; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2014-01-01

    This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions.

  2. Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

    PubMed

    Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A; Davis, Deborah R; Sequeira-Lopez, Maria Luisa S; Cassell, Martin D; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D

    2016-12-01

    The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril, or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of angiotensin-II type 1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin, which was dependent on angiotensin-II type 1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventrolateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension. © 2016 American Heart Association, Inc.

  3. Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI.

    PubMed

    Schwarz, Adam J; Gozzi, Alessandro; Bifone, Angelo

    2009-08-01

    In the study of functional connectivity, fMRI data can be represented mathematically as a network of nodes and links, where image voxels represent the nodes and the connections between them reflect a degree of correlation or similarity in their response. Here we show that, within this framework, functional imaging data can be partitioned into 'communities' of tightly interconnected voxels corresponding to maximum modularity within the overall network. We evaluated this approach systematically in application to networks constructed from pharmacological MRI (phMRI) of the rat brain in response to acute challenge with three different compounds with distinct mechanisms of action (d-amphetamine, fluoxetine, and nicotine) as well as vehicle (physiological saline). This approach resulted in bilaterally symmetric sub-networks corresponding to meaningful anatomical and functional connectivity pathways consistent with the purported mechanism of action of each drug. Interestingly, common features across all three networks revealed two groups of tightly coupled brain structures that responded as functional units independent of the specific neurotransmitter systems stimulated by the drug challenge, including a network involving the prefrontal cortex and sub-cortical regions extending from the striatum to the amygdala. This finding suggests that each of these networks includes general underlying features of the functional organization of the rat brain.

  4. Hierarchical organization of brain functional networks during visual tasks.

    PubMed

    Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

    2011-09-01

    The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

  5. Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

    PubMed Central

    Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

    2015-01-01

    Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

  6. Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

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

    Zhang, Xu; Zhou, Jianying; Chin, Mark H

    2010-02-15

    Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall

  7. Multivariate Heteroscedasticity Models for Functional Brain Connectivity.

    PubMed

    Seiler, Christof; Holmes, Susan

    2017-01-01

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

  8. Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex

    PubMed Central

    Carron, Simone F.; Alwis, Dasuni S.; Rajan, Ramesh

    2016-01-01

    Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat’s exploratory and discriminative tactile system, the large face macrovibrissae, which feeds to the so-called “barrel cortex” of somatosensory cortex. In this review we describe the short-term and long-term changes in the barrel cortex encoding of whisker motion modeling naturalistic whisker movement undertaken by rats engaged in a variety of tasks. We demonstrate that the most common form of TBI results in persistent neuronal hyperexcitation specifically in the upper cortical layers, likely due to changes in inhibition. We describe the types of cortical inhibitory neurons and their roles and how selective effects on some of these could produce the particular forms of neuronal encoding changes described in TBI, and then generalize to compare the effects on inhibition seen in other forms of brain injury. From these findings we make specific predictions as to how non-invasive extra-cranial electrophysiology can be used to provide the high-precision information needed to monitor and understand the temporal evolution of changes in neuronal

  9. Personality Is Reflected in the Brain's Intrinsic Functional Architecture

    PubMed Central

    Adelstein, Jonathan S.; Shehzad, Zarrar; Mennes, Maarten; DeYoung, Colin G.; Zuo, Xi-Nian; Kelly, Clare; Margulies, Daniel S.; Bloomfield, Aaron; Gray, Jeremy R.; Castellanos, F. Xavier; Milham, Michael P.

    2011-01-01

    Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective ‘hubs’ in the brain—the anterior cingulate and precuneus—each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses. PMID:22140453

  10. Structural and functional plasticity specific to musical training with wind instruments.

    PubMed

    Choi, Uk-Su; Sung, Yul-Wan; Hong, Sujin; Chung, Jun-Young; Ogawa, Seiji

    2015-01-01

    Numerous neuroimaging studies have shown structural and functional changes resulting from musical training. Among these studies, changes in primary sensory areas are mostly related to motor functions. In this study, we looked for some similar functional and structural changes in other functional modalities, such as somatosensory function, by examining the effects of musical training with wind instruments. We found significant changes in two aspects of neuroplasticity, cortical thickness, and resting-state neuronal networks. A group of subjects with several years of continuous musical training and who are currently playing in university wind ensembles showed differences in cortical thickness in lip- and tongue-related brain areas vs. non-music playing subjects. Cortical thickness in lip-related brain areas was significantly thicker and that in tongue-related areas was significantly thinner in the music playing group compared with that in the non-music playing group. Association analysis of lip-related areas in the music playing group showed that the increase in cortical thickness was caused by musical training. In addition, seed-based correlation analysis showed differential activation in the precentral gyrus and supplementary motor areas (SMA) between the music and non-music playing groups. These results suggest that high-intensity training with specific musical instruments could induce structural changes in related anatomical areas and could also generate a new functional neuronal network in the brain.

  11. Structural and functional plasticity specific to musical training with wind instruments

    PubMed Central

    Choi, Uk-Su; Sung, Yul-Wan; Hong, Sujin; Chung, Jun-Young; Ogawa, Seiji

    2015-01-01

    Numerous neuroimaging studies have shown structural and functional changes resulting from musical training. Among these studies, changes in primary sensory areas are mostly related to motor functions. In this study, we looked for some similar functional and structural changes in other functional modalities, such as somatosensory function, by examining the effects of musical training with wind instruments. We found significant changes in two aspects of neuroplasticity, cortical thickness, and resting-state neuronal networks. A group of subjects with several years of continuous musical training and who are currently playing in university wind ensembles showed differences in cortical thickness in lip- and tongue-related brain areas vs. non-music playing subjects. Cortical thickness in lip-related brain areas was significantly thicker and that in tongue-related areas was significantly thinner in the music playing group compared with that in the non-music playing group. Association analysis of lip-related areas in the music playing group showed that the increase in cortical thickness was caused by musical training. In addition, seed-based correlation analysis showed differential activation in the precentral gyrus and supplementary motor areas (SMA) between the music and non-music playing groups. These results suggest that high-intensity training with specific musical instruments could induce structural changes in related anatomical areas and could also generate a new functional neuronal network in the brain. PMID:26578939

  12. Efficiency of weak brain connections support general cognitive functioning.

    PubMed

    Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

    2014-09-01

    Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Copyright © 2014 Wiley Periodicals, Inc.

  13. Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas.

    PubMed

    Frenzilli, Giada; Ryskalin, Larisa; Ferrucci, Michela; Cantafora, Emanuela; Chelazzi, Silvia; Giorgi, Filippo S; Lenzi, Paola; Scarcelli, Vittoria; Frati, Alessandro; Biagioni, Francesca; Gambardella, Stefano; Falleni, Alessandra; Fornai, Francesco

    2017-01-01

    Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days) after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise.

  14. A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

    PubMed Central

    Viader, Andreu; Ogasawara, Daisuke; Joslyn, Christopher M; Sanchez-Alavez, Manuel; Mori, Simone; Nguyen, William; Conti, Bruno; Cravatt, Benjamin F

    2016-01-01

    Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and –beta (DAGLβ) to neurons and microglia, respectively. Disruption of DAGLβ perturbed eCB-eicosanoid crosstalk specifically in microglia and suppressed neuroinflammatory events in vivo independently of broader effects on eCB content. Mapping the cellular distribution of metabolic enzymes thus identifies pathways for regulating specialized inflammatory responses in the brain while avoiding global alterations in CNS function. DOI: http://dx.doi.org/10.7554/eLife.12345.001 PMID:26779719

  15. 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."

  16. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    PubMed

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

  17. Development of large-scale functional brain networks in children.

    PubMed

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-07-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

  18. Development of Large-Scale Functional Brain Networks in Children

    PubMed Central

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-01-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

  19. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

    PubMed

    Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

    2006-01-01

    aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

  20. Structure and function of complex brain networks

    PubMed Central

    Sporns, Olaf

    2013-01-01

    An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

  1. Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

    PubMed Central

    Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

    2010-01-01

    Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package

  2. Laterality patterns of brain functional connectivity: gender effects.

    PubMed

    Tomasi, Dardo; Volkow, Nora D

    2012-06-01

    Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).

  3. Laterality Patterns of Brain Functional Connectivity: Gender Effects

    PubMed Central

    Tomasi, Dardo; Volkow, Nora D.

    2012-01-01

    Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism). PMID:21878483

  4. Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

    PubMed

    Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

    2015-06-01

    The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

  5. Cognitive accuracy and intelligent executive function in the brain and in business.

    PubMed

    Bailey, Charles E

    2007-11-01

    This article reviews research on cognition, language, organizational culture, brain, behavior, and evolution to posit the value of operating with a stable reference point based on cognitive accuracy and a rational bias. Drawing on rational-emotive behavioral science, social neuroscience, and cognitive organizational science on the one hand and a general model of brain and frontal lobe executive function on the other, I suggest implications for organizational success. Cognitive thought processes depend on specific brain structures functioning as effectively as possible under conditions of cognitive accuracy. However, typical cognitive processes in hierarchical business structures promote the adoption and application of subjective organizational beliefs and, thus, cognitive inaccuracies. Applying informed frontal lobe executive functioning to cognition, emotion, and organizational behavior helps minimize the negative effects of indiscriminate application of personal and cultural belief systems to business. Doing so enhances cognitive accuracy and improves communication and cooperation. Organizations operating with cognitive accuracy will tend to respond more nimbly to market pressures and achieve an overall higher level of performance and employee satisfaction.

  6. Abdominal Pain, the Adolescent and Altered Brain Structure and Function

    PubMed Central

    Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L.; Borsook, David; Nurko, Samuel

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in

  7. Abdominal Pain, the Adolescent and Altered Brain Structure and Function.

    PubMed

    Hubbard, Catherine S; Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L; Borsook, David; Nurko, Samuel

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in

  8. 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

  9. Sex-specific predictors of inpatient rehabilitation outcomes after traumatic brain injury

    PubMed Central

    Chan, Vincy; Mollayeva, Tatyana; Ottenbacher, Kenneth J.; Colantonio, Angela

    2016-01-01

    Objective To identify sex-specific predictors of inpatient rehabilitation outcomes among patients with a traumatic brain injury (TBI) from a population based perspective. Design Retrospective cohort study Setting Ontario, Canada Participants Patients in inpatient rehabilitation for a TBI within one year of acute care discharge between 2008/09 and 2011/12 (N=1,730, 70% male, 30% female). Interventions None Main Outcome Measures Inpatient rehabilitation length of stay, total Functional Independence Measure (FIM™) score, and motor and cognitive FIM™ ratings at discharge. Results Sex, as a covariate in multivariable linear regression models, was not a significant predictor of rehabilitation outcomes. While many of the predictors examined were similar across males and females, sex-specific multivariable models identified some predictors of rehabilitation outcome that are specific for males and females; mechanism of injury (p<.0001) was a significant predictor of functional outcome only among females while comorbidities (p<.0001) was a significant predictor for males only. Conclusions Predictors of outcomes after inpatient rehabilitation differed by sex, providing evidence for a sex-specific approach in planning and resource allocation for inpatient rehabilitation services for patients with TBI. PMID:26836952

  10. 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.

  11. The impacts of pesticide and nicotine exposures on functional brain networks in Latino immigrant workers.

    PubMed

    Bahrami, Mohsen; Laurienti, Paul J; Quandt, Sara A; Talton, Jennifer; Pope, Carey N; Summers, Phillip; Burdette, Jonathan H; Chen, Haiying; Liu, Jing; Howard, Timothy D; Arcury, Thomas A; Simpson, Sean L

    2017-09-01

    Latino immigrants that work on farms experience chronic exposures to potential neurotoxicants, such as pesticides, as part of their work. For tobacco farmworkers there is the additional risk of exposure to moderate to high doses of nicotine. Pesticide and nicotine exposures have been associated with neurological changes in the brain. Long-term exposure to cholinesterase-inhibiting pesticides, such as organophosphates and carbamates, and nicotine place this vulnerable population at risk for developing neurological dysfunction. In this study we examined whole-brain connectivity patterns and brain network properties of Latino immigrant workers. Comparisons were made between farmworkers and non-farmworkers using resting-state functional magnetic resonance imaging data and a mixed-effects modeling framework. We also evaluated how measures of pesticide and nicotine exposures contributed to the findings. Our results indicate that despite having the same functional connectivity density and strength, brain networks in farmworkers had more clustered and modular structures when compared to non-farmworkers. Our findings suggest increased functional specificity and decreased functional integration in farmworkers when compared to non-farmworkers. Cholinesterase activity was associated with population differences in community structure and the strength of brain network functional connections. Urinary cotinine, a marker of nicotine exposure, was associated with the differences in network community structure. Brain network differences between farmworkers and non-farmworkers, as well as pesticide and nicotine exposure effects on brain functional connections in this study, may illuminate underlying mechanisms that cause neurological implications in later life. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

    PubMed Central

    Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

    2016-01-01

    Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new

  13. Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

    PubMed

    Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

    2016-01-01

    Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge

  14. Impact of Zika Virus on adult human brain structure and functional organization.

    PubMed

    Bido-Medina, Richard; Wirsich, Jonathan; Rodríguez, Minelly; Oviedo, Jairo; Miches, Isidro; Bido, Pamela; Tusen, Luis; Stoeter, Peter; Sadaghiani, Sepideh

    2018-06-01

    To determine the impact of Zika virus (ZIKV) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain-Barré Syndrome (GBS)-like manifestations and include symptoms of the central nervous system (CNS). In this first case-control neuroimaging study, we obtained structural and functional magnetic resonance images in nine rare adult patients in the subacute phase, and healthy age- and sex-matched controls. ZIKV patients showed atypical descending and rapidly progressing peripheral nervous system (PNS) manifestations, and importantly, additional CNS presentations such as perceptual deficits. Voxel-based morphometry was utilized to evaluate gray matter volume, and resting state functional connectivity and Network Based Statistics were applied to assess the functional organization of the brain. Gray matter volume was decreased bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes. We provide preliminary evidence for a link between ZIKV neurological complications and changes in adult human brain structure and functional organization, comprising both motor-related regions potentially secondary to prolonged PNS weakness, and nonsomatomotor regions indicative of PNS-independent alternations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the ZIKV-related neuroinflammatory mechanisms in adults are urgently needed, this study indicates that ZIKV infection can lead to an impact on the brain.

  15. Fetal functional imaging portrays heterogeneous development of emerging human brain networks

    PubMed Central

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26–29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity. PMID:25374531

  16. Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

    PubMed

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

  17. Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

    PubMed

    Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

    2015-01-01

    Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Altered brain functional networks in people with Internet gaming disorder: Evidence from resting-state fMRI.

    PubMed

    Wang, Lingxiao; Wu, Lingdan; Lin, Xiao; Zhang, Yifen; Zhou, Hongli; Du, Xiaoxia; Dong, Guangheng

    2016-08-30

    Although numerous neuroimaging studies have detected structural and functional abnormality in specific brain regions and connections in subjects with Internet gaming disorder (IGD), the topological organization of the whole-brain network in IGD remain unclear. In this study, we applied graph theoretical analysis to explore the intrinsic topological properties of brain networks in Internet gaming disorder (IGD). 37 IGD subjects and 35 matched healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan. The functional networks were constructed by thresholding partial correlation matrices of 90 brain regions. Then we applied graph-based approaches to analysis their topological attributes, including small-worldness, nodal metrics, and efficiency. Both IGD and HC subjects show efficient and economic brain network, and small-world topology. Although there was no significant group difference in global topology metrics, the IGD subjects showed reduced regional centralities in the prefrontal cortex, left posterior cingulate cortex, right amygdala, and bilateral lingual gyrus, and increased functional connectivity in sensory-motor-related brain networks compared to the HC subjects. These results imply that people with IGD may be associated with functional network dysfunction, including impaired executive control and emotional management, but enhanced coordination among visual, sensorimotor, auditory and visuospatial systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

    PubMed

    Deng, Dazhi; Jian, Chongdong; Lei, Ling; Zhou, Yijing; McSweeney, Colleen; Dong, Fengping; Shen, Yilun; Zou, Donghua; Wang, Yonggang; Wu, Yuan; Zhang, Limin; Mao, Yingwei

    2017-10-17

    Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 ( DISC1 ), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

  20. Large-Scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses

    PubMed Central

    Xu, Jiansong; Potenza, Marc N.; Calhoun, Vince D.; Zhang, Rubin; Yip, Sarah W.; Wall, John T.; Pearlson, Godfrey D.; Worhunsky, Patrick D.; Garrison, Kathleen A.; Moran, Joseph M.

    2016-01-01

    Functional magnetic resonance imaging (fMRI) studies regularly use univariate general-linear-model-based analyses (GLM). Their findings are often inconsistent across different studies, perhaps because of several fundamental brain properties including functional heterogeneity, balanced excitation and inhibition (E/I), and sparseness of neuronal activities. These properties stipulate heterogeneous neuronal activities in the same voxels and likely limit the sensitivity and specificity of GLM. This paper selectively reviews findings of histological and electrophysiological studies and fMRI spatial independent component analysis (sICA) and reports new findings by applying sICA to two existing datasets. The extant and new findings consistently demonstrate several novel features of brain functional organization not revealed by GLM. They include overlap of large-scale functional networks (FNs) and their concurrent opposite modulations, and no significant modulations in activity of most FNs across the whole brain during any task conditions. These novel features of brain functional organization are highly consistent with the brain’s properties of functional heterogeneity, balanced E/I, and sparseness of neuronal activity, and may help reconcile inconsistent GLM findings. PMID:27592153

  1. Centrality of Social Interaction in Human Brain Function.

    PubMed

    Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

    2015-10-07

    People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    PubMed

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  3. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

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

  4. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

    PubMed

    Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

  5. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

    PubMed Central

    Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

  6. Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

    PubMed

    Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

    2016-01-01

    Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

  7. An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

    PubMed

    Bode, Gerard H; Coué, Gregory; Freese, Christian; Pickl, Karin E; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F J; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J G; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M; Kirkpatrick, C James; Steinbusch, Harry W M; Frank, Hans-Georg; Unger, Ronald E; Martinez-Martinez, Pilar

    2017-04-01

    Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Viewing the functional consequences of traumatic brain injury by using brain SPECT.

    PubMed

    Pavel, D; Jobe, T; Devore-Best, S; Davis, G; Epstein, P; Sinha, S; Kohn, R; Craita, I; Liu, P; Chang, Y

    2006-03-01

    High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

  9. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  10. The gravitational field and brain function.

    PubMed

    Mei, L; Zhou, C D; Lan, J Q; Wang, Z G; Wu, W C; Xue, X M

    1983-01-01

    The frontal cortex is recognized as the highest adaptive control center of the human brain. The principle of the "frontalization" of human brain function offers new possibilities for brain research in space. There is evolutionary and experimental evidence indicating the validity of the principle, including it's role in nervous response to gravitational stimulation. The gravitational field is considered here as one of the more constant and comprehensive factors acting on brain evolution, which has undergone some successive crucial steps: "encephalization", "corticalization", "lateralization" and "frontalization". The dominating effects of electrical responses from the frontal cortex have been discovered 1) in experiments under gravitational stimulus; and 2) in processes potentially relating to gravitational adaptation, such as memory and learning, sensory information processing, motor programing, and brain state control. A brain research experiment during space flight is suggested to test the role of the frontal cortex in space adaptation and it's potentiality in brain control.

  11. Stimulation of functional vision in children with perinatal brain damage.

    PubMed

    Alimović, Sonja; Mejaski-Bosnjak, Vlatka

    2011-01-01

    Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.

  12. Distinctive Correspondence Between Separable Visual Attention Functions and Intrinsic Brain Networks

    PubMed Central

    Ruiz-Rizzo, Adriana L.; Neitzel, Julia; Müller, Hermann J.; Sorg, Christian; Finke, Kathrin

    2018-01-01

    Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's “theory of visual attention” (TVA) allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity) and selectivity functions (i.e., top-down control and spatial laterality). However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower) visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less) efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable visual attention

  13. Distinctive Correspondence Between Separable Visual Attention Functions and Intrinsic Brain Networks.

    PubMed

    Ruiz-Rizzo, Adriana L; Neitzel, Julia; Müller, Hermann J; Sorg, Christian; Finke, Kathrin

    2018-01-01

    Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's "theory of visual attention" (TVA) allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity) and selectivity functions (i.e., top-down control and spatial laterality). However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower) visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less) efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable visual attention

  14. Left and Right Hemisphere Brain Functions and Symbolic vs. Spontaneous Communication Processes.

    ERIC Educational Resources Information Center

    Buck, Ross

    Recent findings on the communicative functions of the left versus the right hemisphere of the brain may suggest that there is a distinction between the intentional use of symbols for the sending of specific messages or propositions (language, signing, pantomime) and spontaneous expressive behaviors that signal their meaning through a natural…

  15. Progesterone Receptors: Form and Function in Brain

    PubMed Central

    Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

    2008-01-01

    Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

  16. 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

  17. 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.

  18. Extraversion modulates functional connectivity hubs of resting-state brain networks.

    PubMed

    Pang, Yajing; Cui, Qian; Duan, Xujun; Chen, Heng; Zeng, Ling; Zhang, Zhiqiang; Lu, Guangming; Chen, Huafu

    2017-09-01

    Personality dimension extraversion describes individual differences in social behaviour and socio-emotional functioning. The intrinsic functional connectivity patterns of the brain are reportedly associated with extraversion. However, whether or not extraversion is associated with functional hubs warrants clarification. Functional hubs are involved in the rapid integration of neural processing, and their dysfunction contributes to the development of neuropsychiatric disorders. In this study, we employed the functional connectivity density (FCD) method for the first time to distinguish the energy-efficient hubs associated with extraversion. The resting-state functional magnetic resonance imaging data of 71 healthy subjects were used in the analysis. Short-range FCD was positively correlated with extraversion in the left cuneus, revealing a link between the local functional activity of this region and extraversion in risk-taking. Long-range FCD was negatively correlated with extraversion in the right superior frontal gyrus and the inferior frontal gyrus. Seed-based resting-state functional connectivity (RSFC) analyses revealed that a decreased long-range FCD in individuals with high extraversion scores showed a low long-range functional connectivity pattern between the medial and dorsolateral prefrontal cortex, middle temporal gyrus, and anterior cingulate cortex. This result suggests that decreased RSFC patterns are responsible for self-esteem, self-evaluation, and inhibitory behaviour system that account for the modulation and shaping of extraversion. Overall, our results emphasize specific brain hubs, and reveal long-range functional connections in relation to extraversion, thereby providing a neurobiological basis of extraversion. © 2015 The British Psychological Society.

  19. Regional brain volumetry and brain function in severely brain-injured patients.

    PubMed

    Annen, Jitka; Frasso, Gianluca; Crone, Julia Sophia; Heine, Lizette; Di Perri, Carol; Martial, Charlotte; Cassol, Helena; Demertzi, Athena; Naccache, Lionel; Laureys, Steven

    2018-04-01

    The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853. © 2018 American Neurological Association.

  20. Default mode of brain function in monkeys.

    PubMed

    Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A; Buckner, Randy L; Vanduffel, Wim

    2011-09-07

    Human neuroimaging has revealed a specific network of brain regions-the default-mode network (DMN)-that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment.

  1. Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study

    PubMed Central

    Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.

    2010-01-01

    Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting. PMID:20039023

  2. Evidence for hubs in human functional brain networks

    PubMed Central

    Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

    2013-01-01

    Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

  3. The Anatomical Distance of Functional Connections Predicts Brain Network Topology in Health and Schizophrenia

    PubMed Central

    Vértes, Petra E.; Stidd, Reva; Lalonde, François; Clasen, Liv; Rapoport, Judith; Giedd, Jay; Bullmore, Edward T.; Gogtay, Nitin

    2013-01-01

    The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive “pruning” of short-distance functional connections in schizophrenia. PMID:22275481

  4. The temporal structures and functional significance of scale-free brain activity

    PubMed Central

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  5. The relationship between spatial configuration and functional connectivity of brain regions

    PubMed Central

    Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C

    2018-01-01

    Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used ‘functional connectivity fingerprints’ to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. PMID:29451491

  6. The relationship between spatial configuration and functional connectivity of brain regions.

    PubMed

    Bijsterbosch, Janine Diane; Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C; Harrison, Samuel J; Smith, Stephen M

    2018-02-16

    Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used 'functional connectivity fingerprints' to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. © 2018, Bijsterbosch et al.

  7. Brain Targeting Delivery Facilitated by Ligand-Functionalized Layered Double Hydroxide Nanoparticles.

    PubMed

    Chen, Weiyu; Zuo, Huali; Zhang, Enqi; Li, Li; Henrich-Noack, Petra; Cooper, Helen; Qian, Yujin; Xu, Zhi Ping

    2018-06-20

    A delivery platform with highly selective permeability through the blood-brain barrier (BBB) is essential for brain disease treatment. In this research, we designed and prepared a novel target nanoplatform, that is, layered double hydroxide (LDH) nanoparticle conjugated with targeting peptide-ligand Angiopep-2 (Ang2) or rabies virus glycoprotein (RVG) via intermatrix bovine serum albumin for brain targeting. In vitro studies show that functionalization with the target ligand significantly increases the delivery efficiency of LDH nanoparticles to the brain endothelial (bEnd.3) cells and the transcytosis through the simulated BBB model, that is, bEnd.3 cell-constructed multilayer membrane. In vivo confocal neuroimaging of the rat's blood-retina area dynamically demonstrates that LDH nanoparticles modified with peptide ligands have shown a prolonged retention period within the retina vessel in comparison with the pristine LDH group. Moreover, Ang2-modified LDH nanoparticles are found to more specifically accumulate in the mouse brain than the control and RVG-modified LDH nanoparticles after 2 and 48 h intravenous injection. All these findings strongly suggest that Ang2-modified LDHs can serve as an effective targeting nanoplatform for brain disease treatment.

  8. Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury

    PubMed Central

    Dimitriadis, Stavros I.; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C.

    2015-01-01

    Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI. PMID:26640764

  9. [Determinism and Freedom of Choice in the Brain Functioning].

    PubMed

    Ivanitsky, A M

    2015-01-01

    The problem is considered whether the brain response is completely determined by the stimulus and the personal experience or in some cases the brain is free to choose its behavioral response to achieve the desired goal. The attempt is made to approach to this important philosophical problem basing on modern knowledge about the brain. The paper consists of four parts. In the first part the theoretical views about the free choice problem solving are considered, including views about the freedom of choice as a useful illusion, the hypothesis on appliance of quantum mechanics laws to the brain functioning and the theory of mentalism. In other tree parts consequently the more complicated brain functions such as choice reaction, thinking and creation are analyzed. The general conclusion is that the possibility of quite unpredictable, but sometimes very effective decisions increases when the brain functions are more and more complicated. This fact can be explained with two factors: increasing stochasticity of the brain processes and the role of top-down determinations from mental to neural levels, according to the theory of mentalism.

  10. Modalities of Thinking: State and Trait Effects on Cross-Frequency Functional Independent Brain Networks.

    PubMed

    Milz, Patricia; Pascual-Marqui, Roberto D; Lehmann, Dietrich; Faber, Pascal L

    2016-05-01

    Functional states of the brain are constituted by the temporally attuned activity of spatially distributed neural networks. Such networks can be identified by independent component analysis (ICA) applied to frequency-dependent source-localized EEG data. This methodology allows the identification of networks at high temporal resolution in frequency bands of established location-specific physiological functions. EEG measurements are sensitive to neural activity changes in cortical areas of modality-specific processing. We tested effects of modality-specific processing on functional brain networks. Phasic modality-specific processing was induced via tasks (state effects) and tonic processing was assessed via modality-specific person parameters (trait effects). Modality-specific person parameters and 64-channel EEG were obtained from 70 male, right-handed students. Person parameters were obtained using cognitive style questionnaires, cognitive tests, and thinking modality self-reports. EEG was recorded during four conditions: spatial visualization, object visualization, verbalization, and resting. Twelve cross-frequency networks were extracted from source-localized EEG across six frequency bands using ICA. RMANOVAs, Pearson correlations, and path modelling examined effects of tasks and person parameters on networks. Results identified distinct state- and trait-dependent functional networks. State-dependent networks were characterized by decreased, trait-dependent networks by increased alpha activity in sub-regions of modality-specific pathways. Pathways of competing modalities showed opposing alpha changes. State- and trait-dependent alpha were associated with inhibitory and automated processing, respectively. Antagonistic alpha modulations in areas of competing modalities likely prevent intruding effects of modality-irrelevant processing. Considerable research suggested alpha modulations related to modality-specific states and traits. This study identified the

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

    PubMed

    Hari, Riitta

    2017-06-07

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

  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. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease.

    PubMed

    Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E

    2015-07-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD.

  14. Joint Attention and Brain Functional Connectivity in Infants and Toddlers

    PubMed Central

    Eggebrecht, Adam T.; Elison, Jed T.; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J.; Kandala, Sridhar; Adams, Chloe M.; Snyder, Abraham Z.; Lewis, John D.; Estes, Annette M.; Zwaigenbaum, Lonnie; Botteron, Kelly N.; McKinstry, Robert C.; Constantino, John N.; Evans, Alan; Hazlett, Heather C.; Dager, Stephen; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L.; Petersen, Steven E.; Piven, Joseph; Pruett, John R.

    2017-01-01

    Abstract Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. PMID:28062515

  15. Graph analysis of functional brain networks: practical issues in translational neuroscience

    PubMed Central

    De Vico Fallani, Fabrizio; Richiardi, Jonas; Chavez, Mario; Achard, Sophie

    2014-01-01

    The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes. PMID:25180301

  16. Traumatic brain injury shows better functional recovery than brain tumor: a rehabilitative perspective.

    PubMed

    Bilgin, S; Kose, N; Karakaya, J; Mut, M

    2014-02-01

    The similar symptoms seen in the brain tumor (BT) and traumatic brain injury (TBI) population. However, functional comparisons between these two diagnostic groups have been limited. To compare functional outcomes in patients with supratentorial BT and TBI after early rehabilitation. This was a retrospective database analysis. Setting. Patients admitted to an Acute Care Unit as inpatient (Hacettepe Hospital, Ankara-Turkey). Population. The population included patients with BT and TBI. Thirty-four patients with BT and TBI were matched one-to-one by lesion side and sex. The Barthel Index was used to assess functional status at the pre- and postrehabilitation. The change rate and efficiency in BI were also calculated. The time between injury onset and admission to rehabilitation (the onset to admission interval, OAI) and length of stay in rehabilitation (LOS rehab) were recorded. In addition, the influence of lesion side (left and right) and age on functional outcome were analyzed. The functional level was significantly lower in TBI patients than in patients BT before rehabilitation (P<0.05). The post-rehabilitation BI score was similar in patients with BT and TBI (P>0.05). Patients with TBI had greater the change rate and efficiency in BI (P<0.05). The OAI and LOS rehab was longer in patients with TBI (P<0.05). In terms of lesion side comparisons, no differences were found (P>0.05). The age had no effect on functional outcome in patients with TBI and BT (P>0.05), expect the age group 45-59 (P<0.05). The early rehabilitation program improved functional ability of patients with brain tumors, as well as patients with traumatic brain injury. Despite the lower functional status, patients with TBI displayed better functional recovery than patients with BT. Lesion side had no effect on functional outcome in patients with TBI and BT. Differences in functional status begin to appear even in patients with TBI between 45 and 59 years. Further investigations with more detailed

  17. Functional connectivity of the rodent brain using optical imaging

    NASA Astrophysics Data System (ADS)

    Guevara Codina, Edgar

    showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

  18. Psychotropic medication, psychiatric disorders, and higher brain functions

    PubMed Central

    Schulz, Pierre; Steimer, Thierry

    2000-01-01

    Conventional psychiatric diagnosis is founded on symptom description; this then governs the choice of psychotropic medication. This purely descriptive approach resembles a description of diphtheria from the premicrobiology era. Based on current advances in basic and clinical neuroscience, we propose inserting an intermediate level of analysis between psychiatric symptoms and pharmacologic modes of action. Paradigm 1 is to analyze psychiatric symptoms in terms of which higher brain function(s) is (are) abnormal, ie, symptoms should be analyzed as higher brain dysfunction: a case study in obsessive-compulsive disorder reveals pointers in four common symptoms to the higher functions of working memory, emotional overlay, absence of voluntary control, and the ability to evaluate personal mental phenomena. Paradigm 2 is to view psychotropic drugs as modifying normal higher brain functions, rather than merely treating symptoms, which they do only secondarily: thus depression may respond to agents that act on related aspects of mental life derived from higher brain functions, eg, the ability to enhance bonding. We advocate a strategy in which psychiatric illness is progressively reclassified through knowledge in clinical neuroscience and treatment targets are revised accordingly. PMID:22034249

  19. Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

    PubMed

    Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

    2017-10-06

    Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Hierarchical organization of functional connectivity in the mouse brain: a complex network approach.

    PubMed

    Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

    2016-08-18

    This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

  1. Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

    NASA Astrophysics Data System (ADS)

    Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

    2016-08-01

    This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

  2. Functional magnetic resonance imaging reflects changes in brain functioning with sedation.

    PubMed

    Starbuck, Victoria N; Kay, Gary G; Platenberg, R. Craig; Lin, Chin-Shoou; Zielinski, Brandon A

    2000-12-01

    Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd.

  3. Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

    PubMed

    Herbst, Eric A F; Holloway, Graham P

    2015-02-15

    Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits

  4. 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.

  5. Functional split brain in a driving/listening paradigm.

    PubMed

    Sasai, Shuntaro; Boly, Melanie; Mensen, Armand; Tononi, Giulio

    2016-12-13

    We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or to a radio show (split task). We found that, compared with the integrated task, the split task was characterized by reduced multivariate functional connectivity between the driving and listening networks. Furthermore, the integrated information content of the two networks, predicting their joint dynamics above and beyond their independent dynamics, was high in the integrated task and zero in the split task. Finally, individual subjects' ability to switch between high and low information integration predicted their driving performance across integrated and split tasks. This study raises the possibility that under certain conditions of daily life, a single brain may support two independent functional streams, a "functional split brain" similar to what is observed in patients with an anatomical split.

  6. Confounding Brain Stem Function During Pediatric Brain Death Determination: Two Case Reports.

    PubMed

    Hansen, Gregory; Joffe, Ari R

    2017-06-01

    A patient who has been declared brain dead is considered to be both legally and clinically dead. However, we report 2 pediatric cases in which the patients demonstrated clinical signs of brain stem function that are not recognized or tested in current Canadian or US guidelines.

  7. Reduced brain resting-state network specificity in infants compared with adults.

    PubMed

    Wylie, Korey P; Rojas, Donald C; Ross, Randal G; Hunter, Sharon K; Maharajh, Keeran; Cornier, Marc-Andre; Tregellas, Jason R

    2014-01-01

    Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults. Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups. Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults. We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience.

  8. Relationship between diet, the gut microbiota, and brain function.

    PubMed

    Tengeler, Anouk C; Kozicz, Tamas; Kiliaan, Amanda J

    2018-04-28

    The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

  9. Functional Brain Networks: Does the Choice of Dependency Estimator and Binarization Method Matter?

    NASA Astrophysics Data System (ADS)

    Jalili, Mahdi

    2016-07-01

    The human brain can be modelled as a complex networked structure with brain regions as individual nodes and their anatomical/functional links as edges. Functional brain networks are constructed by first extracting weighted connectivity matrices, and then binarizing them to minimize the noise level. Different methods have been used to estimate the dependency values between the nodes and to obtain a binary network from a weighted connectivity matrix. In this work we study topological properties of EEG-based functional networks in Alzheimer’s Disease (AD). To estimate the connectivity strength between two time series, we use Pearson correlation, coherence, phase order parameter and synchronization likelihood. In order to binarize the weighted connectivity matrices, we use Minimum Spanning Tree (MST), Minimum Connected Component (MCC), uniform threshold and density-preserving methods. We find that the detected AD-related abnormalities highly depend on the methods used for dependency estimation and binarization. Topological properties of networks constructed using coherence method and MCC binarization show more significant differences between AD and healthy subjects than the other methods. These results might explain contradictory results reported in the literature for network properties specific to AD symptoms. The analysis method should be seriously taken into account in the interpretation of network-based analysis of brain signals.

  10. Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation.

    PubMed

    Gratton, Caterina; Laumann, Timothy O; Nielsen, Ashley N; Greene, Deanna J; Gordon, Evan M; Gilmore, Adrian W; Nelson, Steven M; Coalson, Rebecca S; Snyder, Abraham Z; Schlaggar, Bradley L; Dosenbach, Nico U F; Petersen, Steven E

    2018-04-18

    The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity

    PubMed Central

    Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

    2014-01-01

    Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity. PMID:24926242

  12. Structural architecture supports functional organization in the human aging brain at a regionwise and network level.

    PubMed

    Zimmermann, Joelle; Ritter, Petra; Shen, Kelly; Rothmeier, Simon; Schirner, Michael; McIntosh, Anthony R

    2016-07-01

    Functional interactions in the brain are constrained by the underlying anatomical architecture, and structural and functional networks share network features such as modularity. Accordingly, age-related changes of structural connectivity (SC) may be paralleled by changes in functional connectivity (FC). We provide a detailed qualitative and quantitative characterization of the SC-FC coupling in human aging as inferred from resting-state blood oxygen-level dependent functional magnetic resonance imaging and diffusion-weighted imaging in a sample of 47 adults with an age range of 18-82. We revealed that SC and FC decrease with age across most parts of the brain and there is a distinct age-dependency of regionwise SC-FC coupling and network-level SC-FC relations. A specific pattern of SC-FC coupling predicts age more reliably than does regionwise SC or FC alone (r = 0.73, 95% CI = [0.7093, 0.8522]). Hence, our data propose that regionwise SC-FC coupling can be used to characterize brain changes in aging. Hum Brain Mapp 37:2645-2661, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

    PubMed

    Eggebrecht, Adam T; Elison, Jed T; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J; Kandala, Sridhar; Adams, Chloe M; Snyder, Abraham Z; Lewis, John D; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan; Hazlett, Heather C; Dager, Stephen; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L; Petersen, Steven E; Piven, Joseph; Pruett, John R

    2017-03-01

    Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.

  14. Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

    PubMed

    Li, Tao; Wang, Qiang; Zhang, Jie; Rolls, Edmund T; Yang, Wei; Palaniyappan, Lena; Zhang, Lu; Cheng, Wei; Yao, Ye; Liu, Zhaowen; Gong, Xiaohong; Luo, Qiang; Tang, Yanqing; Crow, Timothy J; Broome, Matthew R; Xu, Ke; Li, Chunbo; Wang, Jijun; Liu, Zhening; Lu, Guangming; Wang, Fei; Feng, Jianfeng

    2017-03-01

    Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis. © The Author 2016. Published by

  15. Spectral mapping of brain functional connectivity from diffusion imaging.

    PubMed

    Becker, Cassiano O; Pequito, Sérgio; Pappas, George J; Miller, Michael B; Grafton, Scott T; Bassett, Danielle S; Preciado, Victor M

    2018-01-23

    Understanding the relationship between the dynamics of neural processes and the anatomical substrate of the brain is a central question in neuroscience. On the one hand, modern neuroimaging technologies, such as diffusion tensor imaging, can be used to construct structural graphs representing the architecture of white matter streamlines linking cortical and subcortical structures. On the other hand, temporal patterns of neural activity can be used to construct functional graphs representing temporal correlations between brain regions. Although some studies provide evidence that whole-brain functional connectivity is shaped by the underlying anatomy, the observed relationship between function and structure is weak, and the rules by which anatomy constrains brain dynamics remain elusive. In this article, we introduce a methodology to map the functional connectivity of a subject at rest from his or her structural graph. Using our methodology, we are able to systematically account for the role of structural walks in the formation of functional correlations. Furthermore, in our empirical evaluations, we observe that the eigenmodes of the mapped functional connectivity are associated with activity patterns associated with different cognitive systems.

  16. EEG-based research on brain functional networks in cognition.

    PubMed

    Wang, Niannian; Zhang, Li; Liu, Guozhong

    2015-01-01

    Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders.

  17. Brain SPECT scans in students with specific learning disability: Preliminary results.

    PubMed

    Karande, S; Deshmukh, N; Rangarajan, V; Agrawal, A; Sholapurwala, R

    2018-06-08

    Brain single-photon emission computed tomography (SPECT) assesses brain function through measurement of regional cerebral blood flow. This study was conducted to assess whether students with newly diagnosed specific learning disability (SpLD) show any abnormalities in cerebral cortex perfusion. Cross-sectional single-arm pilot study in two tertiary care hospitals. Nine students with SpLD were enrolled. Brain SPECT scan was done twice in each student. For the first or "baseline" scan, the student was first made to sit with eyes open in a quiet, dimly lit room for a period of 30-40 min and then injected intravenously with 20 mCi of 99mTc-ECD. An hour later, "baseline scan" was conducted. After a minimum gap of 4 days, a second or "test scan" was conducted, wherein the student performed an age-appropriate curriculum-based test for a period of 30-40 min to activate the areas in central nervous system related to learning before being injected with 20 mCi of 99mTc-ECD. Cerebral cortex perfusion at rest and after activation in each student was compared qualitatively by visual analysis and quantitatively using NeuroGam TM software. Visual analysis showed reduction in regional blood flow in temporoparietal areas in both "baseline" and "test" scans. However, when normalization was attempted and comparison done by Talairach analysis using NeuroGam software, no statistically significant change in regional perfusion in temporoparietal areas was appreciated. Brain SPECT scan may serve as a robust tool to identify changes in regional brain perfusion in students with SpLD.

  18. Homological scaffolds of brain functional networks

    PubMed Central

    Petri, G.; Expert, P.; Turkheimer, F.; Carhart-Harris, R.; Nutt, D.; Hellyer, P. J.; Vaccarino, F.

    2014-01-01

    Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo. PMID:25401177

  19. Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

    PubMed

    Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

    2017-09-01

    There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A preliminary study of the effects of working memory training on brain function.

    PubMed

    Stevens, Michael C; Gaynor, Alexandra; Bessette, Katie L; Pearlson, Godfrey D

    2016-06-01

    Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed™) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.

  1. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  2. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

  3. From brain topography to brain topology: relevance of graph theory to functional neuroscience.

    PubMed

    Minati, Ludovico; Varotto, Giulia; D'Incerti, Ludovico; Panzica, Ferruccio; Chan, Dennis

    2013-07-10

    Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed

  4. Sex Differences in Brain-Derived Neurotrophic Factor Signaling and Functions

    PubMed Central

    Chan, Chi Bun; Ye, Keqiang

    2016-01-01

    Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies report that some functions or action mechanisms of BDNF vary in a sex-dependent manner. In particular, BDNF content in some brain parts and the tendency of developing BDNF-deficient-related diseases like depression is higher in female animals. With the support of other relevant studies, it is suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross-talk between BDNF and sex steroids has been detected for decades and some sex steroids like estrogen have a positive regulatory effect to BDNF expression and signaling. Thus, the sex of animal models used is critical when studying the functions of BDNF in vivo. In this review, we will summarize our current findings on the difference in expression, signaling, and functions of BDNF between sexes. We will also discuss the potential mechanisms in mediating these differential responses with a specific emphasis on sex steroids. By presenting and discussing these findings, we encourage taking sex influences into consideration when designing experiments, interpreting results and drawing conclusions. PMID:27870419

  5. Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

    PubMed

    Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

    2010-02-01

    While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

  6. Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

    PubMed Central

    Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

    2016-01-01

    Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

  7. Developmental changes in category-specific brain responses to numbers and letters in a working memory task

    PubMed Central

    Libertus, Melissa E.; Brannon, Elizabeth M.; Pelphrey, Kevin A.

    2009-01-01

    Neuroimaging studies have identified a common network of brain regions involving the prefrontal and parietal cortices across a variety of working memory (WM) tasks. However, previous studies have also reported category-specific dissociations of activation within this network. In this study, we investigated the development of category-specific activation in a WM task with digits, letters, and faces. Eight-year-old children and adults performed a 2-back WM task while their brain activity was measured using functional magnetic resonance imaging (fMRI). Overall, children were significantly slower and less accurate than adults on all three WM conditions (digits, letters, and faces); however, within each age group, behavioral performance across the three conditions was very similar. FMRI results revealed category-specific activation in adults but not children in the intraparietal sulcus for the digit condition. Likewise, during the letter condition, category-specific activation was observed in adults but not children in the left occipital–temporal cortex. In contrast, children and adults showed highly similar brain-activity patterns in the lateral fusiform gyri when solving the 2-back WM task with face stimuli. Our results suggest that 8-year-old children do not yet engage the typical brain regions that have been associated with abstract or semantic processing of numerical symbols and letters when these processes are task-irrelevant and the primary task is demanding. Nevertheless, brain activity in letter-responsive areas predicted children’s spelling performance underscoring the relationship between abstract processing of letters and linguistic abilities. Lastly, behavioral performance on the WM task was predictive of math and language abilities highlighting the connection between WM and other cognitive abilities in development. PMID:19027079

  8. MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

    PubMed Central

    Telford, Ryan; Vattoth, Surjith

    2014-01-01

    Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

  9. [The Influence of the Functioning of Brain Regulatory Systems onto the Voluntary Regulation of Cognitive Performance in Children. Report 2. Neuropsychological and Electrophysiological Assessment of Brain Regulatory Functions in Children Aged 10-12 with Learning Difficulties].

    PubMed

    Semenova, O A; Machinskaya, R I

    2015-01-01

    A total number of 172 children aged 10-12 were electrophysiologically and neuropsychologically assessed in order to analyze the influence of the functioning of brain regulatory systems onto the voluntary regulation of cognitive performance during the preteen years. EEG patterns associated with the nonoptimal functioning of brain regulatory systems, particularly fronto-thalamic, limbic and fronto-striatal structures were significantly more often observed in children with learning and behavioral difficulties, as compared to the control group. Neuropsychological assessment showed that the nonoptimal functioning of different brain regulatory systems specifically affect the voluntary regulation of cognitive performance. Children with EEG patterns of fronto-thalamic nonoptimal functioning demonstrated poor voluntary regulation such as impulsiveness and difficulties in continuing the same algorithms. Children with EEG patterns of limbic nonoptimal functioning showed a less pronounced executive dysfunction manifested only in poor switching between program units within a task. Children with EEG patterns of fronto-striatal nonoptimal functioning struggled with such executive dysfunctions as motor and tactile perseverations and emotional-motivational deviations such as poor motivation and communicative skills.

  10. Default Mode of Brain Function in Monkeys

    PubMed Central

    Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

    2013-01-01

    Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

  11. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

    2012-01-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…

  12. Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality.

    PubMed

    Mongerson, Chandler R L; Jennings, Russell W; Borsook, David; Becerra, Lino; Bajic, Dusica

    2017-01-01

    Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used.

  13. Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

    PubMed

    Lesku, John A; Vyssotski, Alexei L; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C

    2011-08-22

    The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

  14. Support vector machine classification and characterization of age-related reorganization of functional brain networks

    PubMed Central

    Meier, Timothy B.; Desphande, Alok S.; Vergun, Svyatoslav; Nair, Veena A.; Song, Jie; Biswal, Bharat B.; Meyerand, Mary E.; Birn, Rasmus M.; Prabhakaran, Vivek

    2012-01-01

    Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5 mm3 radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual’s three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in

  15. Support vector machine classification and characterization of age-related reorganization of functional brain networks.

    PubMed

    Meier, Timothy B; Desphande, Alok S; Vergun, Svyatoslav; Nair, Veena A; Song, Jie; Biswal, Bharat B; Meyerand, Mary E; Birn, Rasmus M; Prabhakaran, Vivek

    2012-03-01

    Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in

  16. Abnormal rich club organization and functional brain dynamics in schizophrenia.

    PubMed

    van den Heuvel, Martijn P; Sporns, Olaf; Collin, Guusje; Scheewe, Thomas; Mandl, René C W; Cahn, Wiepke; Goñi, Joaquín; Hulshoff Pol, Hilleke E; Kahn, René S

    2013-08-01

    The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia. To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics. Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling. Our findings provide novel biological evidence that schizophrenia is characterized by a selective

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

    PubMed

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

    2018-06-01

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

  18. Effect of tumor resection on the characteristics of functional brain networks.

    PubMed

    Wang, H; Douw, L; Hernández, J M; Reijneveld, J C; Stam, C J; Van Mieghem, P

    2010-08-01

    Brain functioning such as cognitive performance depends on the functional interactions between brain areas, namely, the functional brain networks. The functional brain networks of a group of patients with brain tumors are measured before and after tumor resection. In this work, we perform a weighted network analysis to understand the effect of neurosurgery on the characteristics of functional brain networks. Statistically significant changes in network features have been discovered in the beta (13-30 Hz) band after neurosurgery: the link weight correlation around nodes and within triangles increases which implies improvement in local efficiency of information transfer and robustness; the clustering of high link weights in a subgraph becomes stronger, which enhances the global transport capability; and the decrease in the synchronization or virus spreading threshold, revealed by the increase in the largest eigenvalue of the adjacency matrix, which suggests again the improvement of information dissemination.

  19. An Evolutionary Computation Approach to Examine Functional Brain Plasticity.

    PubMed

    Roy, Arnab; Campbell, Colin; Bernier, Rachel A; Hillary, Frank G

    2016-01-01

    One common research goal in systems neurosciences is to understand how the functional relationship between a pair of regions of interest (ROIs) evolves over time. Examining neural connectivity in this way is well-suited for the study of developmental processes, learning, and even in recovery or treatment designs in response to injury. For most fMRI based studies, the strength of the functional relationship between two ROIs is defined as the correlation between the average signal representing each region. The drawback to this approach is that much information is lost due to averaging heterogeneous voxels, and therefore, the functional relationship between a ROI-pair that evolve at a spatial scale much finer than the ROIs remain undetected. To address this shortcoming, we introduce a novel evolutionary computation (EC) based voxel-level procedure to examine functional plasticity between an investigator defined ROI-pair by simultaneously using subject-specific BOLD-fMRI data collected from two sessions seperated by finite duration of time. This data-driven procedure detects a sub-region composed of spatially connected voxels from each ROI (a so-called sub-regional-pair) such that the pair shows a significant gain/loss of functional relationship strength across the two time points. The procedure is recursive and iteratively finds all statistically significant sub-regional-pairs within the ROIs. Using this approach, we examine functional plasticity between the default mode network (DMN) and the executive control network (ECN) during recovery from traumatic brain injury (TBI); the study includes 14 TBI and 12 healthy control subjects. We demonstrate that the EC based procedure is able to detect functional plasticity where a traditional averaging based approach fails. The subject-specific plasticity estimates obtained using the EC-procedure are highly consistent across multiple runs. Group-level analyses using these plasticity estimates showed an increase in the strength

  20. Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

    PubMed

    Curado, Marco; Fritsch, Brita; Reis, Janine

    2016-02-04

    Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

  1. Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

    PubMed

    Schwedt, Todd J; Chong, Catherine D

    2017-07-01

    Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

  2. Distinct patterns of functional brain connectivity correlate with objective performance and subjective beliefs

    PubMed Central

    Barttfeld, Pablo; Wicker, Bruno; McAleer, Phil; Belin, Pascal; Cojan, Yann; Graziano, Martín; Leiguarda, Ramón; Sigman, Mariano

    2013-01-01

    The degree of correspondence between objective performance and subjective beliefs varies widely across individuals. Here we demonstrate that functional brain network connectivity measured before exposure to a perceptual decision task covaries with individual objective (type-I performance) and subjective (type-II performance) accuracy. Increases in connectivity with type-II performance were observed in networks measured while participants directed attention inward (focus on respiration), but not in networks measured during states of neutral (resting state) or exogenous attention. Measures of type-I performance were less sensitive to the subjects’ specific attentional states from which the networks were derived. These results suggest the existence of functional brain networks indexing objective performance and accuracy of subjective beliefs distinctively expressed in a set of stable mental states. PMID:23801762

  3. Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review

    PubMed Central

    Ferraz da Silva, Igor; Freitas-Lima, Leandro Ceotto; Graceli, Jones Bernardes; Rodrigues, Lívia Carla de Melo

    2018-01-01

    The consequences of exposure to environmental contaminants have shown significant effects on brain function and behavior in different experimental models. The endocrine-disrupting chemicals (EDC) present various classes of pollutants with potential neurotoxic actions, such as organotins (OTs). OTs have received special attention due to their toxic effects on the central nervous system, leading to abnormal mammalian neuroendocrine axis function. OTs are organometallic pollutants with a tin atom bound to one or more carbon atoms. OT exposure may occur through the food chain and/or contaminated water, since they have multiple applications in industry and agriculture. In addition, OTs have been used with few legal restrictions in the last decades, despite being highly toxic. In addition to their action as EDC, OTs can also cross the blood–brain barrier and show relevant neurotoxic effects, as observed in several animal model studies specifically involving the development of neurodegenerative processes, neuroinflammation, and oxidative stress. Thus, the aim of this short review is to summarize the toxic effects of the most common OT compounds, such as trimethyltin, tributyltin, triethyltin, and triphenyltin, on the brain with a focus on neuronal damage as a result of oxidative stress and neuroinflammation. We also aim to present evidence for the disruption of behavioral functions, neurotransmitters, and neuroendocrine pathways caused by OTs. PMID:29358929

  4. Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

    PubMed

    Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

    2015-10-01

    Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

  5. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

    PubMed Central

    Zhang, Jiyong; Sadowska, Grazyna B.; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A.; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Stonestreet, Barbara S.

    2015-01-01

    Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

  6. Child gender influences paternal behavior, language, and brain function

    PubMed Central

    Mascaro, Jennifer S.; Rentscher, Kelly E.; Hackett, Patrick D.; Mehl, Matthias R.; Rilling, James K.

    2017-01-01

    Multiple lines of research indicate that fathers often treat boys and girls differently in ways that impact child outcomes. The complex picture that has emerged, however, is obscured by methodological challenges inherent to the study of parental caregiving, and no studies to date have examined the possibility that gender differences in observed real-world paternal behavior are related to differential paternal brain responses to male and female children. Here we compare fathers of daughters and fathers of sons in terms of naturalistically observed everyday caregiving behavior and neural responses to child picture stimuli. Compared to fathers of sons, fathers of daughters were more attentively engaged with their daughters, sang more to their daughters, used more analytical language and language related to sadness and the body with their daughters, and had a stronger neural response to their daughter’s happy facial expressions in areas of the brain important for reward and emotion regulation (medial and lateral orbitofrontal cortex [OFC]). In contrast, fathers of sons engaged in more rough and tumble play (RTP), used more achievement language with their sons, and had a stronger neural response to their son’s neutral facial expressions in the medial OFC (mOFC). Whereas the mOFC response to happy faces was negatively related to RTP, the mOFC response to neutral faces was positively related to RTP, specifically for fathers of boys. These results indicate that real world paternal behavior and brain function differ as a function of child gender. PMID:28541079

  7. Control channels in the brain and their influence on brain executive functions

    NASA Astrophysics Data System (ADS)

    Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

    2014-05-01

    In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

  8. Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach.

    PubMed

    Sartori, Juliana M; Reckziegel, Ramiro; Passos, Ives Cavalcante; Czepielewski, Leticia S; Fijtman, Adam; Sodré, Leonardo A; Massuda, Raffael; Goi, Pedro D; Vianna-Sulzbach, Miréia; Cardoso, Taiane de Azevedo; Kapczinski, Flávio; Mwangi, Benson; Gama, Clarissa S

    2018-08-01

    Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Altered intrinsic functional brain architecture in female patients with bulimia nervosa

    PubMed Central

    Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun’Ai; Correll, Christoph U.; Mitchell, Philip B.; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

    2017-01-01

    Background Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. Methods We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. Results We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. Limitations We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Conclusion Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large

  10. Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

    PubMed

    Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun'Ai; Correll, Christoph U; Mitchell, Philip B; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

    2017-11-01

    Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities

  11. Interpreting and Utilising Intersubject Variability in Brain Function.

    PubMed

    Seghier, Mohamed L; Price, Cathy J

    2018-06-01

    We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

    PubMed Central

    Perez, Julio D; Rubinstein, Nimrod D; Fernandez, Daniel E; Santoro, Stephen W; Needleman, Leigh A; Ho-Shing, Olivia; Choi, John J; Zirlinger, Mariela; Chen, Shau-Kwaun; Liu, Jun S; Dulac, Catherine

    2015-01-01

    The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased—rather than monoallelic—expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain-specific deletion of the paternal, but not maternal, allele of the paternally-biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. DOI: http://dx.doi.org/10.7554/eLife.07860.001 PMID:26140685

  13. In vivo Visuotopic Brain Mapping with Manganese-Enhanced MRI and Resting-State Functional Connectivity MRI

    PubMed Central

    Chan, Kevin C.; Fan, Shu-Juan; Chan, Russell W.; Cheng, Joe S.; Zhou, Iris Y.; Wu, Ed X.

    2014-01-01

    The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the

  14. Functionality predictors in acquired brain damage.

    PubMed

    Huertas Hoyas, E; Pedrero Pérez, E J; Águila Maturana, A M; García López-Alberca, S; González Alted, C

    2015-01-01

    Most individuals who have survived an acquired brain injury present consequences affecting the sensorimotor, cognitive, affective or behavioural components. These deficits affect the proper performance of daily living activities. The aim of this study is to identify functional differences between individuals with unilateral acquired brain injury using functional independence, capacity, and performance of daily activities. Descriptive cross-sectional design with a sample of 58 people, with right-sided injury (n=14 TBI; n=15 stroke) or left-sided injury (n = 14 TBI, n = 15 stroke), right handed, and with a mean age of 47 years and time since onset of 4 ± 3.65 years. The functional assessment/functional independence measure (FIM/FAM) and the International Classification of Functioning (ICF) were used for the study. The data showed significant differences (P<.000), and a large size effect (dr=0.78) in the cross-sectional estimates, and point to fewer restrictions for patients with a lesion on their right side. The major differences were in the variables 'speaking' and 'receiving spoken messages' (ICF variables), and 'Expression', 'Writing' and 'intelligible speech' (FIM/FAM variables). In the linear regression analysis, the results showed that only 4 FIM/FAM variables, taken together, predict 44% of the ICF variance, which measures the ability of the individual, and up to 52% of the ICF, which measures the individual's performance. Gait alone predicts a 28% of the variance. It seems that individuals with acquired brain injury in the left hemisphere display important differences regarding functional and communication variables. The motor aspects are an important prognostic factor in functional rehabilitation. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Emotion regulation ability varies in relation to intrinsic functional brain architecture

    PubMed Central

    Uchida, Mai; Biederman, Joseph; Gabrieli, John D. E.; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana

    2015-01-01

    This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. PMID:25999363

  16. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.

    PubMed

    Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  17. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

    PubMed Central

    Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  18. Circadian misalignment, reward-related brain function, and adolescent alcohol involvement.

    PubMed

    Hasler, Brant P; Clark, Duncan B

    2013-04-01

    Developmental changes in sleep and circadian rhythms that occur during adolescence may contribute to reward-related brain dysfunction, and consequently increase the risk of alcohol use disorders (AUDs). This review (i) describes marked changes in circadian rhythms, reward-related behavior and brain function, and alcohol involvement that occur during adolescence, (ii) offers evidence that these parallel developmental changes are associated, and (iii) posits a conceptual model by which misalignment between sleep-wake timing and endogenous circadian timing may increase the risk of adolescent AUDs by altering reward-related brain function. The timing of sleep shifts later throughout adolescence, in part due to developmental changes in endogenous circadian rhythms, which tend to become more delayed. This tendency for delayed sleep and circadian rhythms is at odds with early school start times during secondary education, leading to misalignment between many adolescents' sleep-wake schedules and their internal circadian timing. Circadian misalignment is associated with increased alcohol use and other risk-taking behaviors, as well as sleep loss and sleep disturbance. Growing evidence indicates that circadian rhythms modulate the reward system, suggesting that circadian misalignment may impact adolescent alcohol involvement by altering reward-related brain function. Neurocognitive function is also subject to sleep and circadian influence, and thus circadian misalignment may also impair inhibitory control and other cognitive processes relevant to alcohol use. Specifically, circadian misalignment may further exacerbate the cortical-subcortical imbalance within the reward circuit, an imbalance thought to explain increased risk-taking and sensation-seeking during adolescence. Adolescent alcohol use is highly contextualized, however, and thus studies testing this model will also need to consider factors that may influence both circadian misalignment and alcohol use. This review

  19. The Effects of Long-term Abacus Training on Topological Properties of Brain Functional Networks.

    PubMed

    Weng, Jian; Xie, Ye; Wang, Chunjie; Chen, Feiyan

    2017-08-18

    Previous studies in the field of abacus-based mental calculation (AMC) training have shown that this training has the potential to enhance a wide variety of cognitive abilities. It can also generate specific changes in brain structure and function. However, there is lack of studies investigating the impact of AMC training on the characteristics of brain networks. In this study, utilizing graph-based network analysis, we compared topological properties of brain functional networks between an AMC group and a matched control group. Relative to the control group, the AMC group exhibited higher nodal degrees in bilateral calcarine sulcus and increased local efficiency in bilateral superior occipital gyrus and right cuneus. The AMC group also showed higher nodal local efficiency in right fusiform gyrus, which was associated with better math ability. However, no relationship was significant in the control group. These findings provide evidence that long-term AMC training may improve information processing efficiency in visual-spatial related regions, which extend our understanding of training plasticity at the brain network level.

  20. Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

    PubMed Central

    Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

    2013-01-01

    Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

  1. Expression and characterization of a brain-specific protein kinase BSK146 from zebrafish.

    PubMed

    Chou, Chih-Ming; Chen, Yi-Chung; Lee, Ming-Ting; Chen, Gen-Der; Lu, I-Ching; Chen, Shui-Tsung; Huang, Chang-Jen

    2006-02-17

    We have previously identified a novel protein kinase, pk146, in the brain of Tetraodon. In the present study, we cloned the homologous protein kinase gene encoding a protein of 385 amino acid residues from zebrafish. The overall amino acid sequence and the kinase domain of zebrafish BSK146 shows 48% and 69% identity to that of rat sbk, a SH3-containing serine/threonine protein kinase. By whole-mount in situ hybridization and RT-PCR, the expression of bsk146 mRNA was mainly in the brain. To explore the in vivo function of BSK146 during zebrafish development, we used morpholino knockdown approach and found that BSK146 morphants displayed enlarged hindbrain ventricle and smaller eyes. Whole-mount in situ hybridization was further performed to analyze the brain defects in BSK146-MO-injected embryos. The expression of brain-specific markers, such as otx2, pax2.1, and krox20, was found normal in morphant embryos at 24hpf, while expression of pax2.1 exerted changes in midbrain-hindbrain boundary and hindbrain in morphant embryos at 48hpf. These data suggest that BSK146 may play an important role in later ventricle expansion in zebrafish brain development. Although the recombinant BSK146 protein produced in insect cells was active and could phosphorylate both histone H1 and histone 2B, the endogenous substrate of BSK146 in the embryonic brain of zebrafish is not clear at the present time and needs further investigation.

  2. Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease.

    PubMed

    Lv, Kun; Fan, Yi-Hong; Xu, Li; Xu, Mao-Sheng

    2017-05-28

    Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

  3. Brain-Computer Interface with Inhibitory Neurons Reveals Subtype-Specific Strategies.

    PubMed

    Mitani, Akinori; Dong, Mingyuan; Komiyama, Takaki

    2018-01-08

    Brain-computer interfaces have seen an increase in popularity due to their potential for direct neuroprosthetic applications for amputees and disabled individuals. Supporting this promise, animals-including humans-can learn even arbitrary mapping between the activity of cortical neurons and movement of prosthetic devices [1-4]. However, the performance of neuroprosthetic device control has been nowhere near that of limb control in healthy individuals, presenting a dire need to improve the performance. One potential limitation is the fact that previous work has not distinguished diverse cell types in the neocortex, even though different cell types possess distinct functions in cortical computations [5-7] and likely distinct capacities to control brain-computer interfaces. Here, we made a first step in addressing this issue by tracking the plastic changes of three major types of cortical inhibitory neurons (INs) during a neuron-pair operant conditioning task using two-photon imaging of IN subtypes expressing GCaMP6f. Mice were rewarded when the activity of the positive target neuron (N+) exceeded that of the negative target neuron (N-) beyond a set threshold. Mice improved performance with all subtypes, but the strategies were subtype specific. When parvalbumin (PV)-expressing INs were targeted, the activity of N- decreased. However, targeting of somatostatin (SOM)- and vasoactive intestinal peptide (VIP)-expressing INs led to an increase of the N+ activity. These results demonstrate that INs can be individually modulated in a subtype-specific manner and highlight the versatility of neural circuits in adapting to new demands by using cell-type-specific strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

    PubMed

    Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

    2015-05-01

    The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

  5. Brain tissue volumes in relation to cognitive function and risk of dementia.

    PubMed

    Ikram, M Arfan; Vrooman, Henri A; Vernooij, Meike W; den Heijer, Tom; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Koudstaal, Peter J; Breteler, Monique M B

    2010-03-01

    We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n=490; 60-90 years) were non-demented at baseline (1995-1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus. We performed neuropsychological testing at baseline to assess information processing speed, executive function, memory function and global cognitive function. Participants were followed for incident dementia until January 1, 2005. Larger volumes of CSF and WML were associated with worse performance on all neuropsychological tests, and an increased risk of dementia. Smaller WM volume was related to poorer information processing speed and executive function. In contrast, smaller GM volume was associated with worse memory function and increased risk of dementia. When investigating lobar GM volumes, we found that hippocampal volume and temporal GM volume were most strongly associated with risk of dementia, even in persons without objective and subjective cognitive deficits at baseline, followed by frontal and parietal GM volumes. Copyright 2008 Elsevier Inc. All rights reserved.

  6. The structural and functional brain networks that support human social networks.

    PubMed

    Noonan, M P; Mars, R B; Sallet, J; Dunbar, R I M; Fellows, L K

    2018-02-20

    Social skills rely on a specific set of cognitive processes, raising the possibility that individual differences in social networks are related to differences in specific brain structural and functional networks. Here, we tested this hypothesis with multimodality neuroimaging. With diffusion MRI (DMRI), we showed that differences in structural integrity of particular white matter (WM) tracts, including cingulum bundle, extreme capsule and arcuate fasciculus were associated with an individual's social network size (SNS). A voxel-based morphology analysis demonstrated correlations between gray matter (GM) volume and SNS in limbic and temporal lobe regions. These structural changes co-occured with functional network differences. As a function of SNS, dorsomedial and dorsolateral prefrontal cortex showed altered resting-state functional connectivity with the default mode network (DMN). Finally, we integrated these three complementary methods, interrogating the relationship between social GM clusters and specific WM and resting-state networks (RSNs). Probabilistic tractography seeded in these GM nodes utilized the SNS-related WM pathways. Further, the spatial and functional overlap between the social GM clusters and the DMN was significantly closer than other control RSNs. These integrative analyses provide convergent evidence of the role of specific circuits in SNS, likely supporting the adaptive behavior necessary for success in extensive social environments. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  7. Tracing Activity Across the Whole Brain Neural Network with Optogenetic Functional Magnetic Resonance Imaging

    PubMed Central

    Lee, Jin Hyung

    2011-01-01

    Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non-invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID:22046160

  8. Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

    PubMed

    Lorenzetti, Valentina; Alonso-Lana, Silvia; Youssef, George J; Verdejo-Garcia, Antonio; Suo, Chao; Cousijn, Janna; Takagi, Michael; Yücel, Murat; Solowij, Nadia

    2016-01-01

    Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Nicotine effects on brain function and functional connectivity in schizophrenia.

    PubMed

    Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

    2004-04-15

    Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

  10. Functional brain imaging in neuropsychology over the past 25 years.

    PubMed

    Roalf, David R; Gur, Ruben C

    2017-11-01

    Outline effects of functional neuroimaging on neuropsychology over the past 25 years. Functional neuroimaging methods and studies will be described that provide a historical context, offer examples of the utility of neuroimaging in specific domains, and discuss the limitations and future directions of neuroimaging in neuropsychology. Tracking the history of publications on functional neuroimaging related to neuropsychology indicates early involvement of neuropsychologists in the development of these methodologies. Initial progress in neuropsychological application of functional neuroimaging has been hampered by costs and the exposure to ionizing radiation. With rapid evolution of functional methods-in particular functional MRI (fMRI)-neuroimaging has profoundly transformed our knowledge of the brain. Its current applications span the spectrum of normative development to clinical applications. The field is moving toward applying sophisticated statistical approaches that will help elucidate distinct neural activation networks associated with specific behavioral domains. The impact of functional neuroimaging on clinical neuropsychology is more circumscribed, but the prospects remain enticing. The theoretical insights and empirical findings of functional neuroimaging have been led by many neuropsychologists and have transformed the field of behavioral neuroscience. Thus far they have had limited effects on the clinical practices of neuropsychologists. Perhaps it is time to add training in functional neuroimaging to the clinical neuropsychologist's toolkit and from there to the clinic or bedside. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality

    PubMed Central

    Mongerson, Chandler R. L.; Jennings, Russell W.; Borsook, David; Becerra, Lino; Bajic, Dusica

    2017-01-01

    Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used. PMID:28856131

  12. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

    PubMed

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

  13. Adaptive functioning following pediatric traumatic brain injury: Relationship to executive function and processing speed.

    PubMed

    Shultz, Emily L; Hoskinson, Kristen R; Keim, Madelaine C; Dennis, Maureen; Taylor, H Gerry; Bigler, Erin D; Rubin, Kenneth H; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen

    2016-10-01

    Pediatric traumatic brain injury (TBI) may affect children's ability to perform everyday tasks (i.e., adaptive functioning). Guided by the American Association for Intellectual and Developmental Disabilities (AAIDD) model, we explored the association between TBI and adaptive functioning at increasing levels of specificity (global, AAIDD domains, and subscales). We also examined the contributions of executive function and processing speed as mediators of TBI's effects on adaptive functioning. Children (ages 8-13) with severe TBI (STBI; n = 19), mild-moderate TBI (MTBI; n = 50), or orthopedic injury (OI; n = 60) completed measures of executive function (TEA-Ch) and processing speed (WISC-IV) an average of 2.7 years postinjury (SD = 1.2; range: 1-5.3). Parents rated children's adaptive functioning (ABAS-II, BASC-2, CASP). STBI had lower global adaptive functioning (η2 = .04-.08) than the MTBI and OI groups, which typically did not differ. Deficits in the STBI group were particularly evident in the social domain, with specific deficits in social participation, leisure, and social adjustment (η2 = .06-.09). Jointly, executive function and processing speed were mediators of STBI's effects on global adaptive functioning and in conceptual and social domains. In the STBI group, executive function mediated social functioning, and processing speed mediated social participation. Children with STBI experience deficits in adaptive functioning, particularly in social adjustment, with less pronounced deficits in conceptual and practical skills. Executive function and processing speed may mediate the effects of STBI on adaptive functioning. Targeting adaptive functioning and associated cognitive deficits for intervention may enhance quality of life for pediatric TBI survivors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Adaptive functioning following pediatric traumatic brain injury: Relationship to executive function and processing speed

    PubMed Central

    Shultz, Emily; Robinson, Kristen E.; Keim, Madelaine; Dennis, Maureen; Taylor, H. Gerry; Bigler, Erin D.; Rubin, Kenneth H.; Vannatta, Kathryn; Gerhardt, Cynthia A.; Stancin, Terry; Yeates, Keith Owen

    2016-01-01

    Objective Pediatric traumatic brain injury (TBI) may affect children’s ability to perform everyday tasks (i.e., adaptive functioning). Guided by the American Association for Intellectual and Developmental Disabilities (AAIDD) model, we explored the association between TBI and adaptive functioning at increasing levels of specificity (global, AAIDD domains, and subscales). We also examined the contributions of executive function and processing speed as mediators of TBI’s effects on adaptive functioning. Method Children (ages 8–13) with severe TBI (STBI; n=19), mild-moderate TBI (MTBI; n=50), or orthopedic injury (OI; n=60) completed measures of executive function (TEA-Ch) and processing speed (WISC-IV) an average of 2.7 years post-injury (SD = 1.2; range: 1–5.3). Parents rated children’s adaptive functioning (ABAS-II, BASC-2, CASP). Results STBI had lower global adaptive functioning (η2 = .04–.08) than the MTBI and OI groups, which typically did not differ. Deficits in the STBI group were particularly evident in the social domain, with specific deficits in social participation, leisure, and social adjustment (η2 = .06–.09). Jointly, executive function and processing speed were mediators of STBI’s effects on global adaptive functioning and in conceptual and social domains. In the STBI group, executive function mediated social functioning, and processing speed mediated social participation. Conclusions Children with STBI experience deficits in adaptive functioning, particularly in social adjustment, with less pronounced deficits in conceptual and practical skills. Executive function and processing speed may mediate the effects of STBI on adaptive functioning. Targeting adaptive functioning and associated cognitive deficits for intervention may enhance quality of life for pediatric TBI survivors. PMID:27182708

  15. Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

    PubMed

    Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

    2018-05-01

    Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Exploring time- and frequency- dependent functional connectivity and brain networks during deception with single-trial event-related potentials

    NASA Astrophysics Data System (ADS)

    Gao, Jun-Feng; Yang, Yong; Huang, Wen-Tao; Lin, Pan; Ge, Sheng; Zheng, Hong-Mei; Gu, Ling-Yun; Zhou, Hui; Li, Chen-Hong; Rao, Ni-Ni

    2016-11-01

    To better characterize the cognitive processes and mechanisms that are associated with deception, wavelet coherence was employed to evaluate functional connectivity between different brain regions. Two groups of subjects were evaluated for this purpose: 32 participants were required to either tell the truth or to lie when facing certain stimuli, and their electroencephalogram signals on 12 electrodes were recorded. The experimental results revealed that deceptive responses elicited greater connectivity strength than truthful responses, particularly in the θ band on specific electrode pairs primarily involving connections between the prefrontal/frontal and central regions and between the prefrontal/frontal and left parietal regions. These results indicate that these brain regions play an important role in executing lying responses. Additionally, three time- and frequency-dependent functional connectivity networks were proposed to thoroughly reflect the functional coupling of brain regions that occurs during lying. Furthermore, the wavelet coherence values for the connections shown in the networks were extracted as features for support vector machine training. High classification accuracy suggested that the proposed network effectively characterized differences in functional connectivity between the two groups of subjects over a specific time-frequency area and hence could be a sensitive measurement for identifying deception.

  17. Nicotine increases brain functional network efficiency.

    PubMed

    Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

    2012-10-15

    Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

  18. Nicotine Increases Brain Functional Network Efficiency

    PubMed Central

    Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Laura F.; Tregellas, Jason R.

    2012-01-01

    Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. PMID:22796985

  19. Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

    PubMed

    Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

    2014-01-01

    Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

  20. Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

    PubMed Central

    Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I

    2000-01-01

    OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.
RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.
CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

 PMID:10990503

  1. Correlation between pulmonary function and brain volume in healthy elderly subjects.

    PubMed

    Taki, Yasuyuki; Kinomura, Shigeo; Ebihara, Satoru; Thyreau, Benjamin; Sato, Kazunori; Goto, Ryoi; Kakizaki, Masako; Tsuji, Ichiro; Kawashima, Ryuta; Fukuda, Hiroshi

    2013-06-01

    Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

  2. Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

    PubMed Central

    White, David J.; Congedo, Marco; Ciorciari, Joseph

    2014-01-01

    A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID

  3. Adaptation of brain functional and structural networks in aging.

    PubMed

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  4. Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

    PubMed Central

    Gebauer, Daniela; Fink, Andreas; Kargl, Reinhard; Reishofer, Gernot; Koschutnig, Karl; Purgstaller, Christian; Fazekas, Franz; Enzinger, Christian

    2012-01-01

    Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training. PMID:22693600

  5. Quetiapine modulates functional connectivity in brain aggression networks.

    PubMed

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

    2013-07-15

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

  6. Differences between child and adult large-scale functional brain networks for reading tasks.

    PubMed

    Liu, Xin; Gao, Yue; Di, Qiqi; Hu, Jiali; Lu, Chunming; Nan, Yun; Booth, James R; Liu, Li

    2018-02-01

    Reading is an important high-level cognitive function of the human brain, requiring interaction among multiple brain regions. Revealing differences between children's large-scale functional brain networks for reading tasks and those of adults helps us to understand how the functional network changes over reading development. Here we used functional magnetic resonance imaging data of 17 adults (19-28 years old) and 16 children (11-13 years old), and graph theoretical analyses to investigate age-related changes in large-scale functional networks during rhyming and meaning judgment tasks on pairs of visually presented Chinese characters. We found that: (1) adults had stronger inter-regional connectivity and nodal degree in occipital regions, while children had stronger inter-regional connectivity in temporal regions, suggesting that adults rely more on visual orthographic processing whereas children rely more on auditory phonological processing during reading. (2) Only adults showed between-task differences in inter-regional connectivity and nodal degree, whereas children showed no task differences, suggesting the topological organization of adults' reading network is more specialized. (3) Children showed greater inter-regional connectivity and nodal degree than adults in multiple subcortical regions; the hubs in children were more distributed in subcortical regions while the hubs in adults were more distributed in cortical regions. These findings suggest that reading development is manifested by a shift from reliance on subcortical to cortical regions. Taken together, our study suggests that Chinese reading development is supported by developmental changes in brain connectivity properties, and some of these changes may be domain-general while others may be specific to the reading domain. © 2017 Wiley Periodicals, Inc.

  7. Complex network analysis of brain functional connectivity under a multi-step cognitive task

    NASA Astrophysics Data System (ADS)

    Cai, Shi-Min; Chen, Wei; Liu, Dong-Bai; Tang, Ming; Chen, Xun

    2017-01-01

    Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a multi-step cognitive task involving consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed based on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to the order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and is obviously restricted to the order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse functional connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.

  8. 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

  9. Intrinsic functional connectivity of the brain swallowing network during subliminal esophageal acid stimulation.

    PubMed

    Babaei, A; Siwiec, R M; Kern, M; Douglas Ward, B; Li, S-J; Shaker, R

    2013-12-01

    Intrinsic synchronous fluctuations of the functional magnetic resonance imaging signal are indicative of the underlying 'functional connectivity' (FC) and serve as a technique to study dynamics of the neuronal networks of the human brain. Earlier studies have characterized the functional connectivity of a distributed network of brain regions involved in swallowing, called brain swallowing network (BSN). The potential modulatory effect of esophageal afferent signals on the BSN, however, has not been systematically studied. Fourteen healthy volunteers underwent steady state functional magnetic resonance imaging across three conditions: (i) transnasal catheter placed in the esophagus without infusion; (ii) buffer solution infused at 1 mL/min; and (iii) acidic solution infused at 1 mL/min. Data were preprocessed according to the standard FC analysis pipeline. We determined the correlation coefficient values of pairs of brain regions involved in swallowing and calculated average group FC matrices across conditions. Effects of subliminal esophageal acidification and nasopharyngeal intubation were determined. Subliminal esophageal acid stimulation augmented the overall FC of the right anterior insula and specifically the FC to the left inferior parietal lobule. Conscious stimulation by nasopharyngeal intubation reduced the overall FC of the right posterior insula, particularly the FC to the right prefrontal operculum. The FC of BSN is amenable to modulation by sensory input. The modulatory effect of sensory pharyngoesophageal stimulation on BSN is mainly mediated through changes in the FC of the insula. The alteration induced by subliminal visceral esophageal acid stimulation is in different insular connections compared with that of conscious somatic pharyngeal stimulation. © 2013 John Wiley & Sons Ltd.

  10. Individual diversity of functional brain network economy.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Ganger, Sebastian; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2015-04-01

    On average, brain network economy represents a trade-off between communication efficiency, robustness, and connection cost, although an analogous understanding on an individual level is largely missing. Evaluating resting-state networks of 42 healthy participants with seven Tesla functional magnetic resonance imaging and graph theory revealed that not even half of all possible connections were common across subjects. The strongest similarities among individuals were observed for interhemispheric and/or short-range connections, which may relate to the essential feature of the human brain to develop specialized systems within each hemisphere. Despite this marked variability in individual network architecture, all subjects exhibited equal small-world properties. Furthermore, interdependency between four major network economy metrics was observed across healthy individuals. The characteristic path length was associated with the clustering coefficient (peak correlation r=0.93), the response to network attacks (r=-0.97), and the physical connection cost in three-dimensional space (r=-0.62). On the other hand, clustering was negatively related to attack response (r=-0.75) and connection cost (r=-0.59). Finally, increased connection cost was associated with better response to attacks (r=0.65). This indicates that functional brain networks with high global information transfer also exhibit strong network resilience. However, it seems that these advantages come at the cost of decreased local communication efficiency and increased physical connection cost. Except for wiring length, the results were replicated on a subsample at three Tesla (n=20). These findings highlight the finely tuned interrelationships between different parameters of brain network economy. Moreover, the understanding of the individual diversity of functional brain network economy may provide further insights in the vulnerability to mental and neurological disorders.

  11. Anatomical and functional assemblies of brain BOLD oscillations

    PubMed Central

    Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

    2011-01-01

    Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

  12. Copine1 regulates neural stem cell functions during brain development.

    PubMed

    Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

    2018-01-01

    Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Child gender influences paternal behavior, language, and brain function.

    PubMed

    Mascaro, Jennifer S; Rentscher, Kelly E; Hackett, Patrick D; Mehl, Matthias R; Rilling, James K

    2017-06-01

    Multiple lines of research indicate that fathers often treat boys and girls differently in ways that impact child outcomes. The complex picture that has emerged, however, is obscured by methodological challenges inherent to the study of parental caregiving, and no studies to date have examined the possibility that gender differences in observed real-world paternal behavior are related to differential paternal brain responses to male and female children. Here we compare fathers of daughters and fathers of sons in terms of naturalistically observed everyday caregiving behavior and neural responses to child picture stimuli. Compared with fathers of sons, fathers of daughters were more attentively engaged with their daughters, sang more to their daughters, used more analytical language and language related to sadness and the body with their daughters, and had a stronger neural response to their daughter's happy facial expressions in areas of the brain important for reward and emotion regulation (medial and lateral orbitofrontal cortex [OFC]). In contrast, fathers of sons engaged in more rough and tumble play (RTP), used more achievement language with their sons, and had a stronger neural response to their son's neutral facial expressions in the medial OFC (mOFC). Whereas the mOFC response to happy faces was negatively related to RTP, the mOFC response to neutral faces was positively related to RTP, specifically for fathers of boys. These results indicate that real-world paternal behavior and brain function differ as a function of child gender. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

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

    Ellison, M.D.B.

    The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study comparesmore » in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.« less

  15. Complex Networks - A Key to Understanding Brain Function

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

    Sporns, Olaf

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  16. Complex Networks - A Key to Understanding Brain Function

    ScienceCinema

    Sporns, Olaf

    2017-12-22

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  17. Evolution of human brain functions: the functional structure of human consciousness.

    PubMed

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  18. Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs.

    PubMed

    Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp

    2018-06-06

    Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after

  19. Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

    2017-02-01

    The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference < 0.1cm-1). Image analysis was performed on the attenuation coefficient images to derive quantitative endpoints. We observed a statistically significant difference among the median attenuation coefficients of these five regions (one-way ANOVA, p<0.05). Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

  20. Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury.

    PubMed

    Iraji, Armin; Chen, Hanbo; Wiseman, Natalie; Welch, Robert D; O'Neil, Brian J; Haacke, E Mark; Liu, Tianming; Kou, Zhifeng

    2016-01-01

    Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4-6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that "Action" and "Cognition" are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances.

  1. Functional brain imaging across development.

    PubMed

    Rubia, Katya

    2013-12-01

    The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of "bottom-up" processing regions towards "top-down" fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to

  2. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

    PubMed

    Piwecka, Monika; Glažar, Petar; Hernandez-Miranda, Luis R; Memczak, Sebastian; Wolf, Susanne A; Rybak-Wolf, Agnieszka; Filipchyk, Andrei; Klironomos, Filippos; Cerda Jara, Cledi Alicia; Fenske, Pascal; Trimbuch, Thorsten; Zywitza, Vera; Plass, Mireya; Schreyer, Luisa; Ayoub, Salah; Kocks, Christine; Kühn, Ralf; Rosenmund, Christian; Birchmeier, Carmen; Rajewsky, Nikolaus

    2017-09-22

    Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos , a direct miR-7 target, was enhanced in Cdr1as -deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

    PubMed Central

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

  4. Psychosocial Stress and Brain Function in Adolescent Psychopathology.

    PubMed

    Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

    2017-08-01

    The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

  5. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions

    PubMed Central

    Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

    2016-01-01

    Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future. PMID:27695409

  6. Sleep Restriction Impairs Blood–Brain Barrier Function

    PubMed Central

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

    2014-01-01

    The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

  7. Emotion regulation ability varies in relation to intrinsic functional brain architecture.

    PubMed

    Uchida, Mai; Biederman, Joseph; Gabrieli, John D E; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana; Whitfield-Gabrieli, Susan

    2015-12-01

    This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  8. Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

    PubMed Central

    Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

    2015-01-01

    Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

  9. Robust prediction of individual creative ability from brain functional connectivity.

    PubMed

    Beaty, Roger E; Kenett, Yoed N; Christensen, Alexander P; Rosenberg, Monica D; Benedek, Mathias; Chen, Qunlin; Fink, Andreas; Qiu, Jiang; Kwapil, Thomas R; Kane, Michael J; Silvia, Paul J

    2018-01-30

    People's ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a recently developed method in functional brain imaging analysis-connectome-based predictive modeling-to identify a brain network associated with high-creative ability, using functional magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in a classic divergent thinking task. At the behavioral level, we found a strong correlation between creative thinking ability and self-reported creative behavior and accomplishment in the arts and sciences ( r = 0.54). At the neural level, we found a pattern of functional brain connectivity related to high-creative thinking ability consisting of frontal and parietal regions within default, salience, and executive brain systems. In a leave-one-out cross-validation analysis, we show that this neural model can reliably predict the creative quality of ideas generated by novel participants within the sample. Furthermore, in a series of external validation analyses using data from two independent task fMRI samples and a large task-free resting-state fMRI sample, we demonstrate robust prediction of individual creative thinking ability from the same pattern of brain connectivity. The findings thus reveal a whole-brain network associated with high-creative ability comprised of cortical hubs within default, salience, and executive systems-intrinsic functional networks that tend to work in opposition-suggesting that highly creative people are characterized by the ability to simultaneously engage these large-scale brain networks.

  10. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    PubMed

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; p<0.001) of aged rats compared to young rats, however no significant differences were detected in synaptic levels in the PFC region. Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. An Adaptive Complex Network Model for Brain Functional Networks

    PubMed Central

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

    2009-01-01

    Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

  12. When "altering brain function" becomes "mind control".

    PubMed

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  13. Material-specific difficulties in episodic memory tasks in mild traumatic brain injury.

    PubMed

    Tsirka, Vassiliki; Simos, Panagiotis; Vakis, Antonios; Vourkas, Michael; Arzoglou, Vasileios; Syrmos, Nikolaos; Stavropoulos, Stavros; Micheloyannis, Sifis

    2010-03-01

    The study examines acute, material-specific secondary memory performance in 26 patients with mild traumatic brain injury (MTBI) and 26 healthy controls, matched on demographic variables and indexes of crystallized intelligence. Neuropsychological tests were used to evaluate primary and secondary memory, executive functions, and verbal fluency. Participants were also tested on episodic memory tasks involving words, pseudowords, pictures of common objects, and abstract kaleidoscopic images. Patients showed reduced performance on episodic memory measures, and on tasks associated with visuospatial processing and executive function (Trail Making Test part B, semantic fluency). Significant differences between groups were also noted for correct rejections and response bias on the kaleidoscope task. MTBI patients' reduced performance on memory tasks for complex, abstract stimuli can be attributed to a dysfunction in the strategic component of memory process.

  14. Deconstructing multivariate decoding for the study of brain function.

    PubMed

    Hebart, Martin N; Baker, Chris I

    2017-08-04

    Multivariate decoding methods were developed originally as tools to enable accurate predictions in real-world applications. The realization that these methods can also be employed to study brain function has led to their widespread adoption in the neurosciences. However, prior to the rise of multivariate decoding, the study of brain function was firmly embedded in a statistical philosophy grounded on univariate methods of data analysis. In this way, multivariate decoding for brain interpretation grew out of two established frameworks: multivariate decoding for predictions in real-world applications, and classical univariate analysis based on the study and interpretation of brain activation. We argue that this led to two confusions, one reflecting a mixture of multivariate decoding for prediction or interpretation, and the other a mixture of the conceptual and statistical philosophies underlying multivariate decoding and classical univariate analysis. Here we attempt to systematically disambiguate multivariate decoding for the study of brain function from the frameworks it grew out of. After elaborating these confusions and their consequences, we describe six, often unappreciated, differences between classical univariate analysis and multivariate decoding. We then focus on how the common interpretation of what is signal and noise changes in multivariate decoding. Finally, we use four examples to illustrate where these confusions may impact the interpretation of neuroimaging data. We conclude with a discussion of potential strategies to help resolve these confusions in interpreting multivariate decoding results, including the potential departure from multivariate decoding methods for the study of brain function. Copyright © 2017. Published by Elsevier Inc.

  15. Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

    PubMed

    Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

    2018-01-01

    Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

  16. Semantic domain-specific functional integration for action-related vs. abstract concepts.

    PubMed

    Ghio, Marta; Tettamanti, Marco

    2010-03-01

    A central topic in cognitive neuroscience concerns the representation of concepts and the specific neural mechanisms that mediate conceptual knowledge. Recently proposed modal theories assert that concepts are grounded on the integration of multimodal, distributed representations. The aim of the present work is to complement the available neuropsychological and neuroimaging evidence suggesting partially segregated anatomo-functional correlates for concrete vs. abstract concepts, by directly testing the semantic domain-specific patterns of functional integration between language and modal semantic brain regions. We report evidence from a functional magnetic resonance imaging study, in which healthy participants listened to sentences with either an action-related (actions involving physical entities) or an abstract (no physical entities involved) content. We measured functional integration using dynamic causal modeling, and found that the left superior temporal gyrus was more strongly connected: (1) for action-related vs. abstract sentences, with the left-hemispheric action representation system, including sensorimotor areas; (2) for abstract vs. action-related sentences, with left infero-ventral frontal, temporal, and retrosplenial cingulate areas. A selective directionality effect was observed, with causal modulatory effects exerted by perisylvian language regions on peripheral modal areas, and not vice versa. The observed condition-specific modulatory effects are consistent with embodied and situated language processing theories, and indicate that linguistic areas promote a semantic content-specific reactivation of modal simulations by top-down mechanisms. Copyright 2008 Elsevier Inc. All rights reserved.

  17. What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging

    PubMed Central

    2016-01-01

    When we consider all of the methods we employ to detect brain function, from electrophysiology to optical techniques to functional magnetic resonance imaging (fMRI), we do not really have a ‘golden technique’ that meets all of the needs for studying the brain. We have methods, each of which has significant limitations but provide often complimentary information. Clearly, there are many questions that need to be answered about fMRI, which unlike other methods, allows us to study the human brain. However, there are also extraordinary accomplishments or demonstration of the feasibility of reaching new and previously unexpected scales of function in the human brain. This article reviews some of the work we have pursued, often with extensive collaborations with other co-workers, towards understanding the underlying mechanisms of the methodology, defining its limitations, and developing solutions to advance it. No doubt, our knowledge of human brain function has vastly expanded since the introduction of fMRI. However, methods and instrumentation in this dynamic field have evolved to a state that discoveries about the human brain based on fMRI principles, together with information garnered at a much finer spatial and temporal scale through other methods, are poised to significantly accelerate in the next decade. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574313

  18. What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging.

    PubMed

    Ugurbil, Kamil

    2016-10-05

    When we consider all of the methods we employ to detect brain function, from electrophysiology to optical techniques to functional magnetic resonance imaging (fMRI), we do not really have a 'golden technique' that meets all of the needs for studying the brain. We have methods, each of which has significant limitations but provide often complimentary information. Clearly, there are many questions that need to be answered about fMRI, which unlike other methods, allows us to study the human brain. However, there are also extraordinary accomplishments or demonstration of the feasibility of reaching new and previously unexpected scales of function in the human brain. This article reviews some of the work we have pursued, often with extensive collaborations with other co-workers, towards understanding the underlying mechanisms of the methodology, defining its limitations, and developing solutions to advance it. No doubt, our knowledge of human brain function has vastly expanded since the introduction of fMRI. However, methods and instrumentation in this dynamic field have evolved to a state that discoveries about the human brain based on fMRI principles, together with information garnered at a much finer spatial and temporal scale through other methods, are poised to significantly accelerate in the next decade.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

  19. Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

    PubMed Central

    Oscar-Berman, Marlene

    2013-01-01

    The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff’s syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking — the types of information and abilities tapped by intelligence tests — remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

  20. Integrative Analysis of Brain Region-specific Shank3 Interactomes for Understanding the Heterogeneity of Neuronal Pathophysiology Related to SHANK3 Mutations

    PubMed Central

    Lee, Yeunkum; Kang, Hyojin; Lee, Bokyoung; Zhang, Yinhua; Kim, Yoonhee; Kim, Shinhyun; Kim, Won-Ki; Han, Kihoon

    2017-01-01

    Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Nevertheless, how the different mutations of SHANK3 can lead to such phenotypic diversity remains largely unknown. In this study, we investigated whether Shank3 could form protein complexes in a brain region-specific manner, which might contribute to the heterogeneity of neuronal pathophysiology caused by SHANK3 mutations. To test this, we generated a medial prefrontal cortex (mPFC) Shank3 in vivo interactome consisting of 211 proteins, and compared this protein list with a Shank3 interactome previously generated from mixed hippocampal and striatal (HP+STR) tissues. Unexpectedly, we found that only 47 proteins (about 20%) were common between the two interactomes, while 164 and 208 proteins were specifically identified in the mPFC and HP+STR interactomes, respectively. Each of the mPFC- and HP+STR-specific Shank3 interactomes represents a highly interconnected network. Upon comparing the brain region-enriched proteomes, we found that the large difference between the mPFC and HP+STR Shank3 interactomes could not be explained by differential protein expression profiles among the brain regions. Importantly, bioinformatic pathway analysis revealed that the representative biological functions of the mPFC- and HP+STR-specific Shank3 interactomes were different, suggesting that these interactors could mediate the brain region-specific functions of Shank3. Meanwhile, the

  1. Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury

    PubMed Central

    Iraji, Armin; Chen, Hanbo; Wiseman, Natalie; Welch, Robert D.; O'Neil, Brian J.; Haacke, E. Mark; Liu, Tianming; Kou, Zhifeng

    2016-01-01

    Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4–6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that “Action” and “Cognition” are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances. PMID:26819765

  2. Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior

    PubMed Central

    Dumais, Kelly M.; Veenema, Alexa H.

    2015-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species- specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. PMID:25951955

  3. Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior.

    PubMed

    Dumais, Kelly M; Veenema, Alexa H

    2016-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species-specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. When Neuroscience 'Touches' Architecture: From Hapticity to a Supramodal Functioning of the Human Brain.

    PubMed

    Papale, Paolo; Chiesi, Leonardo; Rampinini, Alessandra C; Pietrini, Pietro; Ricciardi, Emiliano

    2016-01-01

    In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting 'neuro-architecture' as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people-environment relationships, and even provide empirical foundations for a renewed evidence-based design theory.

  6. Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

    PubMed

    Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul

    2016-01-01

    Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto

  7. Mapping brain function in freely moving subjects

    PubMed Central

    Holschneider, Daniel P.; Maarek, Jean-Michel I.

    2014-01-01

    Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject’s natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease. PMID:15465134

  8. Sex-Specific Predictors of Inpatient Rehabilitation Outcomes After Traumatic Brain Injury.

    PubMed

    Chan, Vincy; Mollayeva, Tatyana; Ottenbacher, Kenneth J; Colantonio, Angela

    2016-05-01

    To identify sex-specific predictors of inpatient rehabilitation outcomes among patients with a traumatic brain injury (TBI) from a population-based perspective. Retrospective cohort study. Inpatient rehabilitation. Patients in inpatient rehabilitation for a TBI within 1 year of acute care discharge between 2008/2009 and 2011/2012 (N=1730, 70% men, 30% women). None. Inpatient rehabilitation length of stay, total FIM score, and motor and cognitive FIM ratings at discharge. Sex, as a covariate in multivariable linear regression models, was not a significant predictor of rehabilitation outcomes. Although many of the predictors examined were similar across men and women, sex-specific multivariable models identified some predictors of rehabilitation outcome that are specific for men and women; mechanism of injury (P<.0001) was a significant predictor of functional outcome only among women, whereas comorbidities (P<.0001) was a significant predictor for men only. Predictors of outcomes after inpatient rehabilitation differed by sex, providing evidence for a sex-specific approach in planning and resource allocation for inpatient rehabilitation services for patients with TBI. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  9. Brain functional connectivity and the pathophysiology of schizophrenia.

    PubMed

    Angelopoulos, E

    2014-01-01

    the flow of thought. Outward signs are abrupt and repeated interruptions in the flow of conversation or actions while subjective experience is that of a total and uncontrollable emptying of the mind. In the very limited bibliography regarding TB, the phenomenon is thought to be conceptualized as a disturbance of consciousness that can be attributed to stoppages of continuous information processing due to an increase in the volume of information to be processed. In an attempt to investigate potential expression of the phenomenon on the functional properties of electroencephalographic (EEG) activity, an EEG study was contacted in schizophrenic patients with persisting auditory verbal hallucinations (AVHs) who additionally exhibited TBs. Phase synchronization analyses performed on EEG segments during the experience of TBs showed that synchrony values exhibited a long-range common mode of coupling (grouped behavior) among the left temporal area and the remaining central and frontal brain areas. These common synchrony-fluctuation schemes were observed for 0.5 to 2 s and were detected in a 4-s window following the estimated initiation of the phenomenon. The observation was frequency specific and detected in the broad alpha band region (6-12 Hz). The introduction of synchrony entropy (SE) analysis applied on the cumulative synchrony distribution showed that TB states were characterized by an explicit preference of the system to be functioned at low values of synchrony, while the synchrony values are broadly distributed during the recovery state. The results indicate that during TB states, the phase locking of several brain areas were converged uniformly in a narrow band of low synchrony values and in a distinct time window, impeding thus the ability of the system to recruit and to process information during this time window. The results of this study seem to have greater importance on neuronal correlation of consciousness. The brain is a highly distributed system in which

  10. Quantifying Individual Brain Connectivity with Functional Principal Component Analysis for Networks.

    PubMed

    Petersen, Alexander; Zhao, Jianyang; Carmichael, Owen; Müller, Hans-Georg

    2016-09-01

    In typical functional connectivity studies, connections between voxels or regions in the brain are represented as edges in a network. Networks for different subjects are constructed at a given graph density and are summarized by some network measure such as path length. Examining these summary measures for many density values yields samples of connectivity curves, one for each individual. This has led to the adoption of basic tools of functional data analysis, most commonly to compare control and disease groups through the average curves in each group. Such group differences, however, neglect the variability in the sample of connectivity curves. In this article, the use of functional principal component analysis (FPCA) is demonstrated to enrich functional connectivity studies by providing increased power and flexibility for statistical inference. Specifically, individual connectivity curves are related to individual characteristics such as age and measures of cognitive function, thus providing a tool to relate brain connectivity with these variables at the individual level. This individual level analysis opens a new perspective that goes beyond previous group level comparisons. Using a large data set of resting-state functional magnetic resonance imaging scans, relationships between connectivity and two measures of cognitive function-episodic memory and executive function-were investigated. The group-based approach was implemented by dichotomizing the continuous cognitive variable and testing for group differences, resulting in no statistically significant findings. To demonstrate the new approach, FPCA was implemented, followed by linear regression models with cognitive scores as responses, identifying significant associations of connectivity in the right middle temporal region with both cognitive scores.

  11. 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

  12. Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions

    PubMed Central

    Krakowiak, Paula; Walker, Cheryl K.; Tancredi, Daniel; Hertz-Picciotto, Irva; Van de Water, Judy

    2016-01-01

    Lay Abstract Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of antibodies to fetal brain tissue that have been detected in only 1% of mothers of typically developing children. However, it is unknown what causes these ASD-specific anti-fetal antibodies to be produced. We examined the relationship between ASD-specific anti-fetal antibodies and metabolic conditions during pregnancy in 227 mothers of 2–5 year old children with ASD, enrolled in the CHARGE (Childhood Autism Risk from Genetics and the Environment) Study, and who had blood samples measured for these anti-fetal brain antibodies after study enrollment. Metabolic conditions included diabetes, hypertensive disorders, and prepregnancy obesity or overweight. The presence of ASD-specific anti-fetal brain antibody patterns was more common among mothers diagnosed with diabetes, hypertensive disorders, or overweight during pregnancy compared to healthy mothers, but these differences did not reach statistical significance. In a subset of 145 mothers whose children exhibited severe ASD symptoms, those diagnosed with type 2 or gestational diabetes were nearly 3 times more likely to have ASD-specific anti-fetal antibodies compared to healthy mothers. Further, those diagnosed with gestational diabetes specifically were over 3 times more likely to have these anti-fetal brain antibodies. In this exploratory study, mothers whose children had severe ASD and who were diagnosed with diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later. Scientific Abstract Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD-specific maternal autoantibodies are poorly understood. We sought to determine whether ASD-specific

  13. Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

    PubMed

    Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

    2018-05-15

    Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information

  14. Reorganization of brain function after a short-term behavioral intervention for stuttering.

    PubMed

    Lu, Chunming; Zheng, Lifen; Long, Yuhang; Yan, Qian; Ding, Guosheng; Liu, Li; Peng, Danling; Howell, Peter

    2017-05-01

    This study investigated changes in brain function that occurred over a 7-day behavioral intervention for adults who stutter (AWS). Thirteen AWS received the intervention (AWS+), and 13 AWS did not receive the intervention (AWS-). There were 13 fluent controls (FC-). All participants were scanned before and after the intervention. Whole-brain analysis pre-intervention showed significant differences in task-related brain activation between AWS and FC- in the right inferior frontal cortex (IFC) and left middle temporal cortex, but there were no differences between the two AWS groups. Across the 7-day period of the intervention, AWS+ alone showed a significant increase of brain activation in the left ventral IFC/insula. There were no changes in brain function for the other two groups. Further analysis revealed that the change did not correlate with resting-state functional connectivity (RSFC) that AWS showed in the cerebellum (Lu et al., 2012). However, both changes in task-related brain function and RSFC correlated with changes in speech fluency level. Together, these findings suggest that functional reorganization in a brain region close to the left IFC that shows anomalous function in AWS, occurs after a short-term behavioral intervention for stuttering. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Imaging structural and functional brain networks in temporal lobe epilepsy.

    PubMed

    Bernhardt, Boris C; Hong, Seokjun; Bernasconi, Andrea; Bernasconi, Neda

    2013-10-01

    Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.

  16. Imaging structural and functional brain networks in temporal lobe epilepsy

    PubMed Central

    Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda

    2013-01-01

    Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

  17. Assortative mixing in functional brain networks during epileptic seizures

    NASA Astrophysics Data System (ADS)

    Bialonski, Stephan; Lehnertz, Klaus

    2013-09-01

    We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

  18. Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus.

    PubMed

    Zhang, Jiyong; Sadowska, Grazyna B; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Banks, William A; Stonestreet, Barbara S

    2015-05-01

    Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia. © FASEB.

  19. Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood-brain barrier models.

    PubMed

    Noumbissi, Midrelle E; Galasso, Bianca; Stins, Monique F

    2018-04-23

    The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.

  20. Large-scale functional brain network changes in taxi drivers: evidence from resting-state fMRI.

    PubMed

    Wang, Lubin; Liu, Qiang; Shen, Hui; Li, Hong; Hu, Dewen

    2015-03-01

    Driving a car in the environment is a complex behavior that involves cognitive processing of visual information to generate the proper motor outputs and action controls. Previous neuroimaging studies have used virtual simulation to identify the brain areas that are associated with various driving-related tasks. Few studies, however, have focused on the specific patterns of functional organization in the driver's brain. The aim of this study was to assess differences in the resting-state networks (RSNs) of the brains of drivers and nondrivers. Forty healthy subjects (20 licensed taxi drivers, 20 nondrivers) underwent an 8-min resting-state functional MRI acquisition. Using independent component analysis, three sensory (primary and extrastriate visual, sensorimotor) RSNs and four cognitive (anterior and posterior default mode, left and right frontoparietal) RSNs were retrieved from the data. We then examined the group differences in the intrinsic brain activity of each RSN and in the functional network connectivity (FNC) between the RSNs. We found that the drivers had reduced intrinsic brain activity in the visual RSNs and reduced FNC between the sensory RSNs compared with the nondrivers. The major finding of this study, however, was that the FNC between the cognitive and sensory RSNs became more positively or less negatively correlated in the drivers relative to that in the nondrivers. Notably, the strength of the FNC between the left frontoparietal and primary visual RSNs was positively correlated with the number of taxi-driving years. Our findings may provide new insight into how the brain supports driving behavior. © 2014 Wiley Periodicals, Inc.

  1. Chapter 18: the origins of functional brain imaging in humans.

    PubMed

    Raichle, Marcus E

    2010-01-01

    Functional brain imaging in humans as we presently know it began when the experimental strategies of cognitive psychology were combined with modern brain imaging techniques, first positron emission tomography (PET) and then functional magnetic resonance imaging (fMRI), to examine how brain function supports mental activities. This marriage of disciplines and techniques galvanized the field of cognitive neuroscience, which has rapidly expanded to include a broad range of the social sciences as well as basic scientists interested in the neurophysiology, cell biology and genetics of the imaging signals. While much of this work has transpired over the past couple of decades, its roots can be traced back more than a century.

  2. A primer on brain-machine interfaces, concepts, and technology: a key element in the future of functional neurorestoration.

    PubMed

    Lee, Brian; Liu, Charles Y; Apuzzo, Michael L J

    2013-01-01

    Conventionally, the practice of neurosurgery has been characterized by the removal of pathology, congenital or acquired. The emerging complement to the removal of pathology is surgery for the specific purpose of restoration of function. Advents in neuroscience, technology, and the understanding of neural circuitry are creating opportunities to intervene in disease processes in a reparative manner, thereby advancing toward the long-sought-after concept of neurorestoration. Approaching the issue of neurorestoration from a biomedical engineering perspective is the rapidly growing arena of implantable devices. Implantable devices are becoming more common in medicine and are making significant advancements to improve a patient's functional outcome. Devices such as deep brain stimulators, vagus nerve stimulators, and spinal cord stimulators are now becoming more commonplace in neurosurgery as we utilize our understanding of the nervous system to interpret neural activity and restore function. One of the most exciting prospects in neurosurgery is the technologically driven field of brain-machine interface, also known as brain-computer interface, or neuroprosthetics. The successful development of this technology will have far-reaching implications for patients suffering from a great number of diseases, including but not limited to spinal cord injury, paralysis, stroke, or loss of limb. This article provides an overview of the issues related to neurorestoration using implantable devices with a specific focus on brain-machine interface technology. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Functional split brain in a driving/listening paradigm

    PubMed Central

    Boly, Melanie; Mensen, Armand; Tononi, Giulio

    2016-01-01

    We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or to a radio show (split task). We found that, compared with the integrated task, the split task was characterized by reduced multivariate functional connectivity between the driving and listening networks. Furthermore, the integrated information content of the two networks, predicting their joint dynamics above and beyond their independent dynamics, was high in the integrated task and zero in the split task. Finally, individual subjects’ ability to switch between high and low information integration predicted their driving performance across integrated and split tasks. This study raises the possibility that under certain conditions of daily life, a single brain may support two independent functional streams, a “functional split brain” similar to what is observed in patients with an anatomical split. PMID:27911805

  4. Exercise-mimetic AICAR transiently benefits brain function

    PubMed Central

    Guerrieri, Davide; van Praag, Henriette

    2015-01-01

    Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function. PMID:26286955

  5. Exercise-mimetic AICAR transiently benefits brain function.

    PubMed

    Guerrieri, Davide; van Praag, Henriette

    2015-07-30

    Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.

  6. Brain Research: The Necessity for Separating Sites, Actions and Functions.

    ERIC Educational Resources Information Center

    Meeker, Mary

    Educators, as applied scientists, must work in partnership with investigative scientists who are researching brain functions in order to reach a better understanding of gifted students and students who are intelligent but do not learn. Improper understanding of brain functions can cause gross errors in educational placement. Until recently, the…

  7. Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

    2014-03-01

    The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

  8. [Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

    PubMed

    Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

    2016-12-20

    Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all P <0.005). Multiple comparison analysis showed that compared with patients in the 1-month follow-up, patients in the 3-month follow-up showed that brain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus

  9. Cross-hemispheric functional connectivity in the human fetal brain.

    PubMed

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  10. Sleep restriction impairs blood-brain barrier function.

    PubMed

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

    2014-10-29

    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

  11. Beyond localized and distributed accounts of brain functions. Comment on “Understanding brain networks and brain organization” by Pessoa

    NASA Astrophysics Data System (ADS)

    Cauda, Franco; Costa, Tommaso; Tamietto, Marco

    2014-09-01

    Recent evidence in cognitive neuroscience lends support to the idea that network models of brain architecture provide a privileged access to the understanding of the relation between brain organization and cognitive processes [1]. The core perspective holds that cognitive processes depend on the interactions among distributed neuronal populations and brain structures, and that the impact of a given region on behavior largely depends on its pattern of anatomical and functional connectivity [2,3].

  12. Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study.

    PubMed

    Smagula, Stephen F; Lotrich, Francis E; Aizenstein, Howard J; Diniz, Breno S; Krystek, Jeffrey; Wu, Gregory F; Mulsant, Benoit H; Butters, Meryl A; Reynolds, Charles F; Lenze, Eric J

    2017-06-01

    Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function). Adults (n = 31) were at least 60 years old and had major depressive disorder. A multiplex immunoassay assessed 13 immunological biomarkers, and we examined their associations with structural MRI (grey matter volume and white matter hyperintensity volume (WMH)) and executive function (Color-Word Interference and Trail-Making tests) measures. Vascular endothelial growth factor (VEGF) and the chemokine eotaxin had significant negative associations with grey matter volume (VEGF: n = 31, r = -0.65; eotaxin: n = 29, r = -0.44). Tumor necrosis factor alpha (TNF-α) had a significant positive relationship with WMHs (n = 30, r = 0.52); interferon-γ (IFN-γ) and macrophage inflammatory protein-1α (MIP-1α) were also significantly associated with WMHs (IFN-γ: n = 31, r = 0.48; MIP-1α: n = 29, r = 0.45). Only eotaxin was associated with executive function (set-shifting performance as measured with the Trail-making test: n = 33, r = -0.43). Immunological markers are associated with brain structure in LLD. We found the immunological correlates of grey and white matter differ. Prospective studies are needed to evaluate whether these immunological correlates of brain health increase the risk of LLD's consequences. Eotaxin, which correlated with both grey matter volume and set-shifting performance, may be particularly relevant to neurodegeneration and cognition in LLD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley

  13. Sex on the brain: Are gender-dependent structural and functional differences associated with behavior?

    PubMed

    Grabowska, Anna

    2017-01-02

    A substantial number of studies provide evidence documenting a variety of sex differences in the brain. It remains unclear whether sexual differentiation at the neural level is related to that observed in daily behavior, cognitive function, and the risk of developing certain psychiatric and neurological disorders. Some investigators have questioned whether the brain is truly sexually differentiated and support this view with several arguments including the following: (1) brain structural or functional differences are not necessarily reflected in appropriate differences at the behavioral level, which might suggest that these two phenomena are not linked to each other; and (2) sex-related differences in the brain are rather small and concern features that significantly overlap between males and females. This review polemicizes with those opinions and presents examples of sex-related local neural differences underpinning a variety of sex differences in behaviors, skills, and cognitive/emotional abilities. Although male/female brain differentiation may vary in pattern and scale, nonetheless, in some respects (e.g., relative local gray matter volumes) it can be substantial, taking the form of sexual dimorphism and involving large areas of the brain (the cortex in particular). A significant part of this review is devoted to arguing that some sex differences in the brain may serve to prevent (in the case where they are maladaptive), rather than to produce, differences at the behavioral/skill level. Specifically, some differences might result from compensatory mechanisms aimed at maintaining similar intellectual capacities across the sexes, despite the smaller average volume of the brain in females compared with males. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Mapping the functional connectome in traumatic brain injury: What can graph metrics tell us?

    PubMed

    Caeyenberghs, Karen; Verhelst, Helena; Clemente, Adam; Wilson, Peter H

    2017-10-15

    Traumatic brain injury (TBI) is associated with cognitive and motor deficits, and poses a significant personal, societal, and economic burden. One mechanism by which TBI is thought to affect cognition and behavior is through changes in functional connectivity. Graph theory is a powerful framework for quantifying topological features of neuroimaging-derived functional networks. The objective of this paper is to review studies examining functional connectivity in TBI with an emphasis on graph theoretical analysis that is proving to be valuable in uncovering network abnormalities in this condition. We review studies that have examined TBI-related alterations in different properties of the functional brain network, including global integration, segregation, centrality and resilience. We focus on functional data using task-related fMRI or resting-state fMRI in patients with TBI of different severity and recovery phase, and consider how graph metrics may inform rehabilitation and enhance efficacy. Moreover, we outline some methodological challenges associated with the examination of functional connectivity in patients with brain injury, including the sample size, parcellation scheme used, node definition and subgroup analyses. The findings suggest that TBI is associated with hyperconnectivity and a suboptimal global integration, characterized by increased connectivity degree and strength and reduced efficiency of functional networks. This altered functional connectivity, also evident in other clinical populations, is attributable to diffuse white matter pathology and reductions in gray and white matter volume. These functional alterations are implicated in post-concussional symptoms, posttraumatic stress and neurocognitive dysfunction after TBI. Finally, the effects of focal lesions have been found to depend critically on topological position and their role in the network. Graph theory is a unique and powerful tool for exploring functional connectivity in brain

  15. Predicting individual brain functional connectivity using a Bayesian hierarchical model.

    PubMed

    Dai, Tian; Guo, Ying

    2017-02-15

    Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients. These studies provide the impetus to develop statistical methodology that would help provide predictive information on disease progression-related or treatment-related changes in neural connectivity. To this end, we propose a prediction method based on Bayesian hierarchical model that uses individual's baseline fMRI scans, coupled with relevant subject characteristics, to predict the individual's future functional connectivity. A key advantage of the proposed method is that it can improve the accuracy of individualized prediction of connectivity by combining information from both group-level connectivity patterns that are common to subjects with similar characteristics as well as individual-level connectivity features that are particular to the specific subject. Furthermore, our method also offers statistical inference tools such as predictive intervals that help quantify the uncertainty or variability of the predicted outcomes. The proposed prediction method could be a useful approach to predict the changes in individual patient's brain connectivity with the progression of a disease. It can also be used to predict a patient's post-treatment brain connectivity after a specified treatment regimen. Another utility of the proposed method is that it can be applied to test-retest imaging data to develop a more reliable estimator for individual

  16. Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

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

    Welzel, Grit; Fleckenstein, Katharina; Department of Radiation Oncology, Duke University Medical Center, Durham, NC

    2008-12-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy,more » prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.« less

  17. Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?

    PubMed

    Castro, José Pedro; Wardelmann, Kristina; Grune, Tilman; Kleinridders, André

    2018-01-01

    The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.

  18. Cognitive function and brain structure in females with a history of adolescent-onset anorexia nervosa.

    PubMed

    Chui, Harold T; Christensen, Bruce K; Zipursky, Robert B; Richards, Blake A; Hanratty, M Katherine; Kabani, Noor J; Mikulis, David J; Katzman, Debra K

    2008-08-01

    Abnormalities in cognitive function and brain structure have been reported in acutely ill adolescents with anorexia nervosa, but whether these abnormalities persist or are reversible in the context of weight restoration remains unclear. Brain structure and cognitive function in female subjects with adolescent-onset anorexia nervosa assessed at long-term follow-up were studied in comparison with healthy female subjects, and associations with clinical outcome were investigated. Sixty-six female subjects (aged 21.3 +/- 2.3 years) who had a diagnosis of adolescent-onset anorexia nervosa and treated 6.5 +/- 1.7 years earlier in a tertiary care hospital and 42 healthy female control subjects (aged 20.7 +/- 2.5 years) were assessed. All participants underwent a clinical examination, magnetic resonance brain scan, and cognitive evaluation. Clinical data were analyzed first as a function of weight recovery (n = 14, <85% ideal body weight; n = 52, >or=85% ideal body weight) and as a function of menstrual status (n = 18, absent/irregular menses; n = 29, oral contraceptive pill; n = 19, regular menses). Group comparisons were made across structural brain volumes and cognitive scores. Compared with control subjects, participants with anorexia nervosa who remained at low weight had larger lateral ventricles. Twenty-four-hour urinary free-cortisol levels were positively correlated with volumes of the temporal horns of the lateral ventricles and negatively correlated with volumes of the hippocampi in clinical participants. Participants who were amenorrheic or had irregular menses showed significant cognitive deficits across a broad range of many domains. Female subjects with adolescent-onset anorexia nervosa showed abnormal cognitive function and brain structure compared with healthy individuals despite an extended period since diagnosis. To our knowledge, this is the first study to report a specific relationship between menstrual function and cognitive function in this patient

  19. Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress in specific brain regions in the rat.

    PubMed

    Salchner, Peter; Engidawork, Ephrem; Hoeger, Harald; Lubec, Barbara; Singewald, Nicolas

    2003-09-01

    Perinatal asphyxia (PA) causes irreversible damage to the brain of newborns and can produce neurologic and behavioral changes later in life. To identify neuronal substrates underlying the effects of PA, we investigated whether and how neuronal responsiveness to an established stress challenge is affected. We used Fos expression as a marker of neuronal activation and examined the pattern of Fos expression in response to acute swim stress in 24-month-old rats exposed to a 20-minute PA insult. Swim stress produced a similar pattern of Fos expression in control and asphyxiated rats in 34 brain areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen, and prelimbic cortex. No differences in the Fos response to stress were observed in other regions, including the locus ceruleus, amygdala, hippocampus, or septum. These data provide functional anatomic evidence that PA has lifelong effects on neuronal communication and leads to an abnormal, augmented neuronal responsiveness to stress in specific brain areas, particularly in the main telencephalic target regions of the mesencephalic dopamine projections, as well as in a functionally related set of brain regions associated with autonomic and neuroendocrine regulation.

  20. Changes in functional and structural brain connectome along the Alzheimer's disease continuum.

    PubMed

    Filippi, Massimo; Basaia, Silvia; Canu, Elisa; Imperiale, Francesca; Magnani, Giuseppe; Falautano, Monica; Comi, Giancarlo; Falini, Andrea; Agosta, Federica

    2018-05-09

    The aim of this study was two-fold: (i) to investigate structural and functional brain network architecture in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), stratified in converters (c-aMCI) and non-converters (nc-aMCI) to AD; and to assess the relationship between healthy brain network functional connectivity and the topography of brain atrophy in patients along the AD continuum. Ninety-four AD patients, 47 aMCI patients (25 c-aMCI within 36 months) and 53 age- and sex-matched healthy controls were studied. Graph analysis and connectomics assessed global and local, structural and functional topological network properties and regional connectivity. Healthy topological features of brain regions were assessed based on their connectivity with the point of maximal atrophy (epicenter) in AD and aMCI patients. Brain network graph analysis properties were severely altered in AD patients. Structural brain network was already altered in c-aMCI patients relative to healthy controls in particular in the temporal and parietal brain regions, while functional connectivity did not change. Structural connectivity alterations distinguished c-aMCI from nc-aMCI cases. In both AD and c-aMCI, the point of maximal atrophy was located in left hippocampus (disease-epicenter). Brain regions most strongly connected with the disease-epicenter in the healthy functional connectome were also the most atrophic in both AD and c-aMCI patients. Progressive degeneration in the AD continuum is associated with an early breakdown of anatomical brain connections and follows the strongest connections with the disease-epicenter. These findings support the hypothesis that the topography of brain connectional architecture can modulate the spread of AD through the brain.

  1. The Brain Prize 2014: complex human functions.

    PubMed

    Grigaityte, Kristina; Iacoboni, Marco

    2014-11-01

    Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research? Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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.

  3. A decade of imaging surgeons' brain function (part II): A systematic review of applications for technical and nontechnical skills assessment.

    PubMed

    Modi, Hemel Narendra; Singh, Harsimrat; Yang, Guang-Zhong; Darzi, Ara; Leff, Daniel Richard

    2017-11-01

    Functional neuroimaging technologies enable assessment of operator brain function and can deepen our understanding of skills learning, ergonomic optima, and cognitive processes in surgeons. Although there has been a critical mass of data detailing surgeons' brain function, this literature has not been reviewed systematically. A systematic search of original neuroimaging studies assessing surgeons' brain function and published up until November 2016 was conducted using Medline, Embase, and PsycINFO databases. Twenty-seven studies fulfilled the inclusion criteria, including 3 feasibility studies, 14 studies exploring the neural correlates of technical skill acquisition, and the remainder investigating brain function in the context of intraoperative decision-making (n = 1), neurofeedback training (n = 1), robot-assisted technology (n = 5), and surgical teaching (n = 3). Early stages of learning open surgical tasks (knot-tying) are characterized by prefrontal cortical activation, which subsequently attenuates with deliberate practice. However, with complex laparoscopic skills (intracorporeal suturing), prefrontal cortical engagement requires substantial training, and attenuation occurs over a longer time course, after years of refinement. Neurofeedback and interventions that improve neural efficiency may enhance technical performance and skills learning. Imaging surgeons' brain function has identified neural signatures of expertise that might help inform objective assessment and selection processes. Interventions that improve neural efficiency may target skill-specific brain regions and augment surgical performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Neuroplasticity as a function of second language learning: anatomical changes in the human brain.

    PubMed

    Li, Ping; Legault, Jennifer; Litcofsky, Kaitlyn A

    2014-09-01

    The brain has an extraordinary ability to functionally and physically change or reconfigure its structure in response to environmental stimulus, cognitive demand, or behavioral experience. This property, known as neuroplasticity, has been examined extensively in many domains. But how does neuroplasticity occur in the brain as a function of an individual's experience with a second language? It is not until recently that we have gained some understanding of this question by examining the anatomical changes as well as functional neural patterns that are induced by the learning and use of multiple languages. In this article we review emerging evidence regarding how structural neuroplasticity occurs in the brain as a result of one's bilingual experience. Our review aims at identifying the processes and mechanisms that drive experience-dependent anatomical changes, and integrating structural imaging evidence with current knowledge of functional neural plasticity of language and other cognitive skills. The evidence reviewed so far portrays a picture that is highly consistent with structural neuroplasticity observed for other domains: second language experience-induced brain changes, including increased gray matter (GM) density and white matter (WM) integrity, can be found in children, young adults, and the elderly; can occur rapidly with short-term language learning or training; and are sensitive to age, age of acquisition, proficiency or performance level, language-specific characteristics, and individual differences. We conclude with a theoretical perspective on neuroplasticity in language and bilingualism, and point to future directions for research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis.

    PubMed

    Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K

    2014-05-01

    Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

  6. Brain structural and functional asymmetry in human situs inversus totalis.

    PubMed

    Vingerhoets, Guy; Li, Xiang; Hou, Lewis; Bogaert, Stephanie; Verhelst, Helena; Gerrits, Robin; Siugzdaite, Roma; Roberts, Neil

    2018-05-01

    Magnetic resonance imaging was used to investigate brain structural and functional asymmetries in 15 participants with complete visceral reversal (situs inversus totalis, SIT). Language-related brain structural and functional lateralization of SIT participants, including peri-Sylvian gray and white matter asymmetries and hemispheric language dominance, was similar to those of 15 control participants individually matched for sex, age, education, and handedness. In contrast, the SIT cohort showed reversal of the brain (Yakovlevian) torque (occipital petalia and occipital bending) compared to the control group. Secondary findings suggested different asymmetry patterns between SIT participants with (n = 6) or without (n = 9) primary ciliary dyskinesia (PCD, also known as Kartagener syndrome) although the small sample sizes warrant cautious interpretation. In particular, reversed brain torque was mainly due to the subgroup with PCD-unrelated SIT and this group also included 55% left handers, a ratio close to a random allocation of handedness. We conclude that complete visceral reversal has no effect on the lateralization of brain structural and functional asymmetries associated with language, but seems to reverse the typical direction of the brain torque in particular in participants that have SIT unrelated to PCD. The observed differences in asymmetry patterns of SIT groups with and without PCD seem to suggest that symmetry breaking of visceral laterality, brain torque, and language dominance rely on different mechanisms.

  7. Imaging Brain Function with Functional Near-Infrared Spectroscopy in Unconstrained Environments.

    PubMed

    Balardin, Joana B; Zimeo Morais, Guilherme A; Furucho, Rogério A; Trambaiolli, Lucas; Vanzella, Patricia; Biazoli, Claudinei; Sato, João R

    2017-01-01

    Assessing the neural correlates of motor and cognitive processes under naturalistic experimentation is challenging due to the movement constraints of traditional brain imaging technologies. The recent advent of portable technologies that are less sensitive to motion artifacts such as Functional Near Infrared Spectroscopy (fNIRS) have been made possible the study of brain function in freely-moving participants. In this paper, we describe a series of proof-of-concept experiments examining the potential of fNIRS in assessing the neural correlates of cognitive and motor processes in unconstrained environments. We show illustrative applications for practicing a sport (i.e., table tennis), playing a musical instrument (i.e., piano and violin) alone or in duo and performing daily activities for many hours (i.e., continuous monitoring). Our results expand upon previous research on the feasibility and robustness of fNIRS to monitor brain hemodynamic changes in different real life settings. We believe that these preliminary results showing the flexibility and robustness of fNIRS measurements may contribute by inspiring future work in the field of applied neuroscience.

  8. Imaging Brain Function with Functional Near-Infrared Spectroscopy in Unconstrained Environments

    PubMed Central

    Balardin, Joana B.; Zimeo Morais, Guilherme A.; Furucho, Rogério A.; Trambaiolli, Lucas; Vanzella, Patricia; Biazoli, Claudinei; Sato, João R.

    2017-01-01

    Assessing the neural correlates of motor and cognitive processes under naturalistic experimentation is challenging due to the movement constraints of traditional brain imaging technologies. The recent advent of portable technologies that are less sensitive to motion artifacts such as Functional Near Infrared Spectroscopy (fNIRS) have been made possible the study of brain function in freely-moving participants. In this paper, we describe a series of proof-of-concept experiments examining the potential of fNIRS in assessing the neural correlates of cognitive and motor processes in unconstrained environments. We show illustrative applications for practicing a sport (i.e., table tennis), playing a musical instrument (i.e., piano and violin) alone or in duo and performing daily activities for many hours (i.e., continuous monitoring). Our results expand upon previous research on the feasibility and robustness of fNIRS to monitor brain hemodynamic changes in different real life settings. We believe that these preliminary results showing the flexibility and robustness of fNIRS measurements may contribute by inspiring future work in the field of applied neuroscience. PMID:28567011

  9. Monitoring the injured brain: registered, patient specific atlas models to improve accuracy of recovered brain saturation values

    NASA Astrophysics Data System (ADS)

    Clancy, Michael; Belli, Antonio; Davies, David; Lucas, Samuel J. E.; Su, Zhangjie; Dehghani, Hamid

    2015-07-01

    The subject of superficial contamination and signal origins remains a widely debated topic in the field of Near Infrared Spectroscopy (NIRS), yet the concept of using the technology to monitor an injured brain, in a clinical setting, poses additional challenges concerning the quantitative accuracy of recovered parameters. Using high density diffuse optical tomography probes, quantitatively accurate parameters from different layers (skin, bone and brain) can be recovered from subject specific reconstruction models. This study assesses the use of registered atlas models for situations where subject specific models are not available. Data simulated from subject specific models were reconstructed using the 8 registered atlas models implementing a regional (layered) parameter recovery in NIRFAST. A 3-region recovery based on the atlas model yielded recovered brain saturation values which were accurate to within 4.6% (percentage error) of the simulated values, validating the technique. The recovered saturations in the superficial regions were not quantitatively accurate. These findings highlight differences in superficial (skin and bone) layer thickness between the subject and atlas models. This layer thickness mismatch was propagated through the reconstruction process decreasing the parameter accuracy.

  10. Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

    PubMed

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

  11. Whole Brain Magnetic Resonance Spectroscopic Determinants of Functional Outcomes in Pediatric Moderate/Severe Traumatic Brain Injury.

    PubMed

    Babikian, Talin; Alger, Jeffry R; Ellis-Blied, Monica U; Giza, Christopher C; Dennis, Emily; Olsen, Alexander; Mink, Richard; Babbitt, Christopher; Johnson, Jeff; Thompson, Paul M; Asarnow, Robert F

    2018-05-18

    Diffuse axonal injury contributes to the long-term functional morbidity observed after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain proton magnetic resonance echo-planar spectroscopic imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post-msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and corpus callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an event related potential paradigm) was also explored. Pediatric patients with msTBI underwent assessments at two times (post-acutely at a mean of three months post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24). Healthy controls also underwent two evaluations, approximately 12 months apart. Post-acutely, in patients with msTBI, there were elevations in choline (Cho; marker for inflammation and/or altered membrane metabolism) in all four brain lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and axonal integrity) in the CC compared with controls, all of which normalized by the chronic time point. Subgroups of TBI showed variable patterns chronically. Patients with slow IHTT had lower lobar Cho chronically than those with normal IHTT; they also did not show normalization in CC NAA whereas those with normal IHTT showed significantly higher levels of CC NAA relative to controls. In the normal IHTT group only, chronic CC Cho and NAA together explained 70% of the variance in long-term cognitive functioning. MR based whole brain metabolic evaluations show different patterns of neurochemistry after msTBI in two subgroups with different outcomes. There is a dynamic relationship between prolonged inflammatory responses to brain damage, reparative processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal studies allow us to test hypotheses about degenerative and

  12. Patient-specific semi-supervised learning for postoperative brain tumor segmentation.

    PubMed

    Meier, Raphael; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

    2014-01-01

    In contrast to preoperative brain tumor segmentation, the problem of postoperative brain tumor segmentation has been rarely approached so far. We present a fully-automatic segmentation method using multimodal magnetic resonance image data and patient-specific semi-supervised learning. The idea behind our semi-supervised approach is to effectively fuse information from both pre- and postoperative image data of the same patient to improve segmentation of the postoperative image. We pose image segmentation as a classification problem and solve it by adopting a semi-supervised decision forest. The method is evaluated on a cohort of 10 high-grade glioma patients, with segmentation performance and computation time comparable or superior to a state-of-the-art brain tumor segmentation method. Moreover, our results confirm that the inclusion of preoperative MR images lead to a better performance regarding postoperative brain tumor segmentation.

  13. Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

    PubMed

    Gibson, Daniel A; Ma, Le

    2011-08-01

    Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab

  14. Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

    DTIC Science & Technology

    2015-10-01

    Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

  15. Dysbindin modulates brain function during visual processing in children.

    PubMed

    Mechelli, A; Viding, E; Kumar, A; Pettersson-Yeo, W; Fusar-Poli, P; Tognin, S; O'Donovan, M C; McGuire, P

    2010-01-01

    Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.

  16. [Clinical interest of fMRI and functional exploration methods of brain activity and interactivity: physical and neurophysiological considerations].

    PubMed

    de Marco, G; Menuel, C; Guillevin, R; Vallée, J-N; Lehmann, P; Fall, S; Quaglino, V; Bourdin, B; Devauchelle, B; Chiras, J

    2008-07-01

    After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.

  17. Assessment of a brain-tumour-specific Patient Concerns Inventory in the neuro-oncology clinic.

    PubMed

    Rooney, Alasdair G; Netten, Anouk; McNamara, Shanne; Erridge, Sara; Peoples, Sharon; Whittle, Ian; Hacking, Belinda; Grant, Robin

    2014-04-01

    Brain tumour patients may struggle to express their concerns in the outpatient clinic, creating a physician-focused rather than a shared agenda. We created a simple, practical brain-tumour-specific holistic needs assessment (HNA) tool for use in the neuro-oncology outpatient clinic. We posted the brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult brain tumour attendees to a neuro-oncology outpatient clinic. Participants brought the completed PCI to their clinic consultation. Patients and staff provided feedback. Seventy seven patients were eligible and 53 participated (response rate = 68%). The PCI captured many problems absent from general cancer checklists. The five most frequent concerns were fatigue, fear of tumour coming back, memory, concentration, and low mood. Respondents used the PCI to formulate 105 specific questions, usually about the meaning of physical or psychological symptoms. Patients and staff found the PCI to be useful, and satisfaction with the instrument was high. This study demonstrates the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The combination of a brain-tumour-specific concerns checklist and an intervention to focus patient agenda creates a simple and efficient HNA tool.

  18. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    PubMed Central

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  19. Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

    PubMed Central

    Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

    2016-01-01

    The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

  20. Functional brain networks in schizophrenia: a review.

    PubMed

    Calhoun, Vince D; Eichele, Tom; Pearlson, Godfrey

    2009-01-01

    Functional magnetic resonance imaging (fMRI) has become a major technique for studying cognitive function and its disruption in mental illness, including schizophrenia. The major proportion of imaging studies focused primarily upon identifying regions which hemodynamic response amplitudes covary with particular stimuli and differentiate between patient and control groups. In addition to such amplitude based comparisons, one can estimate temporal correlations and compute maps of functional connectivity between regions which include the variance associated with event-related responses as well as intrinsic fluctuations of hemodynamic activity. Functional connectivity maps can be computed by correlating all voxels with a seed region when a spatial prior is available. An alternative are multivariate decompositions such as independent component analysis (ICA) which extract multiple components, each of which is a spatially distinct map of voxels with a common time course. Recent work has shown that these networks are pervasive in relaxed resting and during task performance and hence provide robust measures of intact and disturbed brain activity. This in turn bears the prospect of yielding biomarkers for schizophrenia, which can be described both in terms of disrupted local processing as well as altered global connectivity between large-scale networks. In this review we will summarize functional connectivity measures with a focus upon work with ICA and discuss the meaning of intrinsic fluctuations. In addition, examples of how brain networks have been used for classification of disease will be shown. We present work with functional network connectivity, an approach that enables the evaluation of the interplay between multiple networks and how they are affected in disease. We conclude by discussing new variants of ICA for extracting maximally group discriminative networks from data. In summary, it is clear that identification of brain networks and their inter

  1. Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

    PubMed

    Bischof, Gérard N; Park, Denise C

    2015-01-01

    This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

  2. Obesity and Aging: Consequences for Cognition, Brain Structure and Brain Function

    PubMed Central

    Bischof, Gérard N.; Park, Denise C.

    2017-01-01

    Objective This review focuses on the relationship between obesity and aging and how these interact together to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC; Park & Reuter-Lorenz, 2009—a conceptual model designed to relate brain structure and function to one’s level of cognitive ability. Methods The initial literature search was focused on normal aging and was guided by the key words, “aging, cognition, and obesity” in “PUBMED”. In a second search we added key words related to neuropathology including words “Alzheimer’s Disease”, “Vascular dementia” (VaD) and “Mild Cognitive Impairment” (MCI). Results The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the lifespan. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in mid-life is linked to an increased risk for AD and VaD, most likely via an increased accumulation of AD pathology. Conclusion While it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the lifespan. PMID:26107577

  3. Association Between Brain Activation and Functional Connectivity.

    PubMed

    Tomasi, Dardo; Volkow, Nora D

    2018-04-13

    The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

  4. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain

    PubMed Central

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the “universal” language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  5. Language comprehension and brain function in individuals with an optimal outcome from autism.

    PubMed

    Eigsti, Inge-Marie; Stevens, Michael C; Schultz, Robert T; Barton, Marianne; Kelley, Elizabeth; Naigles, Letitia; Orinstein, Alyssa; Troyb, Eva; Fein, Deborah A

    2016-01-01

    Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened "compensatory" activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.

  6. Mining Time-Resolved Functional Brain Graphs to an EEG-Based Chronnectomic Brain Aged Index (CBAI).

    PubMed

    Dimitriadis, Stavros I; Salis, Christos I

    2017-01-01

    The brain at rest consists of spatially and temporal distributed but functionally connected regions that called intrinsic connectivity networks (ICNs). Resting state electroencephalography (rs-EEG) is a way to characterize brain networks without confounds associated with task EEG such as task difficulty and performance. A novel framework of how to study dynamic functional connectivity under the notion of functional connectivity microstates (FCμstates) and symbolic dynamics is further discussed. Furthermore, we introduced a way to construct a single integrated dynamic functional connectivity graph (IDFCG) that preserves both the strength of the connections between every pair of sensors but also the type of dominant intrinsic coupling modes (DICM). The whole methodology is demonstrated in a significant and unexplored task for EEG which is the definition of an objective Chronnectomic Brain Aged index (CBAI) extracted from resting-state data ( N = 94 subjects) with both eyes-open and eyes-closed conditions. Novel features have been defined based on symbolic dynamics and the notion of DICM and FCμstates. The transition rate of FCμstates, the symbolic dynamics based on the evolution of FCμstates (the Markovian Entropy, the complexity index), the probability distribution of DICM, the novel Flexibility Index that captures the dynamic reconfiguration of DICM per pair of EEG sensors and the relative signal power constitute a valuable pool of features that can build the proposed CBAI. Here we applied a feature selection technique and Extreme Learning Machine (ELM) classifier to discriminate young adults from middle-aged and a Support Vector Regressor to build a linear model of the actual age based on EEG-based spatio-temporal features. The most significant type of features for both prediction of age and discrimination of young vs. adults age groups was the dynamic reconfiguration of dominant coupling modes derived from a subset of EEG sensor pairs. Specifically, our

  7. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    PubMed

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. An Ultraconserved Brain-specific Enhancer within ADGRL3 (LPHN3) Underpins ADHD Susceptibility

    PubMed Central

    Martinez, Ariel F.; Abe, Yu; Hong, Sungkook; Molyneux, Kevin; Yarnell, David; Löhr, Heiko; Driever, Wolfgang; Acosta, Maria T.; Arcos-Burgos, Mauricio; Muenke, Maximilian

    2016-01-01

    BACKGROUND Genetic factors predispose to attention deficit/hyperactivity disorder (ADHD). Previous studies have reported linkage and association to ADHD of gene variants within ADGRL3. In this study, we functionally analyzed non-coding variants in this gene as likely pathological contributors. METHODS In silico, in vitro and in vivo approaches were used to identify and characterize evolutionary conserved elements within the ADGRL3 linkage region (~207 Kb). Family-based genetic analyses on 838 individuals (372 affected and 466 unaffected) identified ADHD-associated SNPs harbored in some of these conserved elements. Luciferase assays and zebrafish GFP transgenesis tested conserved elements for transcriptional enhancer activity. Electromobility shift assays were used to verify transcription factor binding disruption by ADHD risk alleles. RESULTS An ultraconserved element was discovered (ECR47) that functions as a transcriptional enhancer. A three-variant ADHD risk haplotype in ECR47, formed by rs17226398, rs56038622 and rs2271338, reduced enhancer activity by 40% in neuroblastoma and astrocytoma cells (PBonferroni<0.0001). This enhancer also drove GFP expression in the zebrafish brain in a tissue-specific manner, sharing aspects of endogenous ADGRL3 expression. The rs2271338 risk allele disrupts binding of YY1, an important factor in the development and function of the central nervous system. Expression quantitative trait loci analysis of post-mortem human brain tissues revealed an association between rs2271338 and reduced ADGRL3 expression in the thalamus. CONCLUSIONS These results uncover the first functional evidence of common non-coding variants with potential implications for the pathology of ADHD. PMID:27692237

  9. Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function.

    PubMed

    Pan, Yijun; Short, Jennifer L; Choy, Kwok H C; Zeng, Annie X; Marriott, Philip J; Owada, Yuji; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A

    2016-11-16

    Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5 +/+ and FABP5 -/- mice using a battery of memory paradigms. FABP5 -/- mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring 14 C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5 +/+ and FABP5 -/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA, 14 C-DHA uptake into brain endothelial cells and brain capillaries of FABP5 -/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5 +/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5 -/- mice are associated with reduced CNS access of DHA. Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5 -/- mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role for FABP5

  10. Prenatal famine exposure has sex-specific effects on brain size.

    PubMed

    de Rooij, Susanne R; Caan, Matthan W A; Swaab, Dick F; Nederveen, Aart J; Majoie, Charles B; Schwab, Matthias; Painter, Rebecca C; Roseboom, Tessa J

    2016-08-01

    Early nutritional deprivation might cause irreversible damage to the brain. Prenatal exposure to undernutrition has been shown to be associated with increased central nervous system anomalies at birth and decreased cognitive function in adulthood. Little is known about the potential effect on the brain in older age. We investigated brain size and structure at age 68 years after prenatal famine exposure. T1-weighted structural magnetic resonance images of the brain were made in 118 Dutch famine birth cohort members. Of these 118 (44% male, age range 65-69 years), 41 had been exposed to famine in early gestation and 77 had been prenatally unexposed. Structural volumes were automatically assessed using FreeSurfer. Diffusion tensor imaging was performed and anisotropy and diffusivity were computed. Fluid attenuated inversion recovery was performed to assess white matter hyperintensities. Exposure to famine in early gestation was associated with smaller intracranial volume in males, but not females. Volumes of total brain, grey and white matter were also smaller in early exposed males, but these differences disappeared after adjusting for intracranial volume. Prenatally exposed males but not females, had a smaller intracranial and total brain volume compared to unexposed subjects. Our findings show that prenatal undernutrition permanently affected brain size.media-1vid110.1093/brain/aww132_video_abstractaww132_video_abstract. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Functional brain imaging in respiratory medicine.

    PubMed

    Pattinson, Kyle

    2015-06-01

    Discordance of clinical symptoms with markers of disease severity remains a conundrum in a variety of respiratory conditions. The breathlessness of chronic lung disease correlates poorly with spirometry, yet is a better predictor of mortality. In chronic cough, symptoms are often evident without clear physical cause. In asthma, the terms 'over perceivers' and 'under perceivers' are common parlance. In all these examples, aberrant brain mechanisms may explain the mismatch between symptoms and pathology. Functional MRI is a non-invasive method of measuring brain function. It has recently become significantly advanced enough to be useful in clinical research and to address these potential mechanisms. This article explains how FMRI works, current understanding from FMRI in breathlessness, cough and asthma and suggests possibilities for future research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    PubMed

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  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. A genome-wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects.

    PubMed

    Raum, Heidelore; Dietsche, Bruno; Nagels, Arne; Witt, Stephanie H; Rietschel, Marcella; Kircher, Tilo; Krug, Axel

    2015-01-01

    The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the NCAN gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. NCAN encodes neurocan, a brain-specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of NCAN on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the NCAN SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that NCAN risk status, defined as AA or AG genotype, was associated with a lack of task-related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal pole. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in NCAN influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function. © 2014 Wiley Periodicals, Inc.

  15. Species-specific ant brain manipulation by a specialized fungal parasite.

    PubMed

    de Bekker, Charissa; Quevillon, Lauren E; Smith, Philip B; Fleming, Kimberly R; Ghosh, Debashis; Patterson, Andrew D; Hughes, David P

    2014-08-29

    A compelling demonstration of adaptation by natural selection is the ability of parasites to manipulate host behavior. One dramatic example involves fungal species from the genus Ophiocordyceps that control their ant hosts by inducing a biting behavior. Intensive sampling across the globe of ants that died after being manipulated by Ophiocordyceps suggests that this phenomenon is highly species-specific. We advance our understanding of this system by reconstructing host manipulation by Ophiocordyceps parasites under controlled laboratory conditions and combining this with field observations of infection rates and a metabolomics survey. We report on a newly discovered species of Ophiocordyceps unilateralis sensu lato from North America that we use to address the species-specificity of Ophiocordyceps-induced manipulation of ant behavior. We show that the fungus can kill all ant species tested, but only manipulates the behavior of those it infects in nature. To investigate if this could be explained at the molecular level, we used ex vivo culturing assays to measure the metabolites that are secreted by the fungus to mediate fungus-ant tissue interactions. We show the fungus reacts heterogeneously to brains of different ant species by secreting a different array of metabolites. By determining which ion peaks are significantly enriched when the fungus is grown alongside brains of its naturally occurring host, we discovered candidate compounds that could be involved in behavioral manipulation by O. unilateralis s.l.. Two of these candidates are known to be involved in neurological diseases and cancer. The integrative work presented here shows that ant brain manipulation by O. unilateralis s.l. is species-specific seemingly because the fungus produces a specific array of compounds as a reaction to the presence of the host brain it has evolved to manipulate. These studies have resulted in the discovery of candidate compounds involved in establishing behavioral manipulation

  16. Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure

    PubMed Central

    Park, Bumhee; Roy, Bhaswati; Woo, Mary A.; Palomares, Jose A.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

    2016-01-01

    Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID:27203600

  17. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    PubMed

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  18. Brain uptake of multivalent and multi-specific DVD-Ig proteins after systemic administration.

    PubMed

    Karaoglu Hanzatian, Denise; Schwartz, Annette; Gizatullin, Farid; Erickson, Jamie; Deng, Kangwen; Villanueva, Ruth; Stedman, Christopher; Harris, Cristina; Ghayur, Tariq; Goodearl, Andrew

    2018-05-17

    Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would. Dual-variable-domain immunoglobulin (DVD-Ig) proteins offer a bispecific format where monoclonal antibody-like bivalency to both the BBB receptor and the therapeutic target is preserved, enabling independent engineering of binding affinity, potency, valency, epitope and conformation, essential for successful generation of clinical candidates for CNS applications with desired drug-like properties. Each of these parameters can affect the binding and transcytosis ability mediated by different receptors on the brain endothelium differentially, allowing exploration of diverse properties. Here, we describe generation and characterization of several different DVD-Ig proteins, specific for four different CNS targets, capable of crossing the BBB through transcytosis mediated by the transferrin receptor 1 (TfR1). After systemic administration of each DVD-Ig, we used two independent methods in parallel to observe specific uptake into the brain. An electrochemiluminescent-based sensitive quantitative assay and a semi-quantitative immunohistochemistry technique were used for brain concentration determination and biodistribution/localization in brain, respectively. Significantly enhanced brain uptake and retention was observed for all TfR1 DVD-Ig proteins

  19. Salience network integrity predicts default mode network function after traumatic brain injury

    PubMed Central

    Bonnelle, Valerie; Ham, Timothy E.; Leech, Robert; Kinnunen, Kirsi M.; Mehta, Mitul A.; Greenwood, Richard J.; Sharp, David J.

    2012-01-01

    Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)—which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae—regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control. PMID:22393019

  20. Oligodendrocyte-Neuron Interactions: Impact on Myelination and Brain Function.

    PubMed

    Shimizu, Takeshi; Osanai, Yasuyuki; Ikenaka, Kazuhiro

    2018-01-01

    In the past, glial cells were considered to be 'glue' cells whose primary role was thought to be merely filling gaps in neural circuits. However, a growing number of reports have indicated the role of glial cells in higher brain function through their interaction with neurons. Myelin was originally thought to be just a sheath structure surrounding neuronal axons, but recently it has been shown that myelin exerts effects on the conduction velocity of neuronal axons even after myelin formation. Therefore, the investigation of glial cell properties and the neuron-glial interactions is important for understanding higher brain function. Moreover, since there are many neurological disorders caused by glial abnormalities, further understanding of glial cell-related diseases and the development of effective therapeutic strategies are warranted. In this review, we focused on oligodendrocyte-neuron interactions, with particular attention on (1) axonal signals underlying oligodendrocyte differentiation and myelination, (2) neuronal activity-dependent myelination and (3) the effects of myelination on higher brain function.

  1. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    PubMed Central

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  2. Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain

    PubMed Central

    Okamura-Oho, Yuko; Shimokawa, Kazuro; Nishimura, Masaomi; Takemoto, Satoko; Sato, Akira; Furuichi, Teiichi; Yokota, Hideo

    2014-01-01

    Using a recently invented technique for gene expression mapping in the whole-anatomy context, termed transcriptome tomography, we have generated a dataset of 36,000 maps of overall gene expression in the adult-mouse brain. Here, using an informatics approach, we identified a broad co-expression network that follows an inverse power law and is rich in functional interaction and gene-ontology terms. Our framework for the integrated analysis of expression maps and graphs of co-expression networks revealed that groups of combinatorially expressed genes, which regulate cell differentiation during development, were present in the adult brain and each of these groups was associated with a discrete cell types. These groups included non-coding genes of unknown function. We found that these genes specifically linked developmentally conserved groups in the network. A previously unrecognized robust expression pattern covering the whole brain was related to the molecular anatomy of key biological processes occurring in particular areas. PMID:25382412

  3. Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

    ERIC Educational Resources Information Center

    Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

    2006-01-01

    The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

  4. Impact of head morphology on local brain specific absorption rate from exposure to mobile phone radiation.

    PubMed

    Adibzadeh, Fatemeh; Bakker, Jurriaan F; Paulides, Margarethus M; Verhaart, René F; van Rhoon, Gerard C

    2015-01-01

    Among various possible health effects of mobile phone radiation, the risk of inducing cancer has the strongest interest of laymen and health organizations. Recently, the Interphone epidemiological study investigated the association between the estimated Radio Frequency (RF) dose from mobile phones and the risk of developing a brain tumor. Their dosimetric analysis included over 100 phone models but only two homogeneous head phantoms. So, the potential impact of individual morphological features on global and local RF absorption in the brain was not investigated. In this study, we performed detailed dosimetric simulations for 20 head models and quantified the variation of RF dose in different brain regions as a function of head morphology. Head models were exposed to RF fields from generic mobile phones at 835 and 1900 MHz in the "tilted" and "cheek" positions. To evaluate the local RF dose variation, we used and compared two different post-processing methods, that is, averaging specific absorption rate (SAR) over Talairach regions and over sixteen predefined 1 cm(3) cube-shaped field-sensors. The results show that the variation in the averaged SAR among the heads can reach up to 16.4 dB at a 1 cm(3) cube inside the brain (field-sensor method) and alternatively up to 15.8 dB in the medulla region (Talairach method). In conclusion, we show head morphology as an important uncertainty source for dosimetric studies of mobile phones. Therefore, any dosimetric analysis dealing with RF dose at a specific region in the brain (e.g., tumor risk analysis) should be based upon real morphology. © 2014 Wiley Periodicals, Inc.

  5. 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.

  6. Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

    PubMed Central

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

  7. Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.

    PubMed

    Huang, Xiaojun; Pu, Weidan; Liu, Haihong; Li, Xinmin; Greenshaw, Andrew J; Dursun, Serdar M; Xue, Zhimin; Liu, Zhening

    2017-01-01

    Betel quid (BQ) is a common psychoactive substance worldwide with particularly high usage in many Asian countries. This study aimed to explore the effect of BQ use on functional connectivity by comparing global functional brain networks and their subset between BQ chewers and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24 betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T scanner. We used independent component analysis (ICA) to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. Two sample t -tests were used to identify the functional connectivity differences in each network between these two groups. Seventeen networks were identified by ICA. Nine of them showed connectivity differences between BQD and HCs (two sample t -tests, p  < 0.001 uncorrected). We found increased functional connectivity in the orbitofrontal, bilateral frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum, and temporal/limbic networks, and decreased connectivity in the parietal and medial frontal/anterior cingulate networks in the BQD compared to the HCs. The betel quid dependence scale scores were positively related to the increased functional connectivity in the orbitofrontal ( r  = 0.39, p  = 0.03) while negatively related to the decreased functional connectivity in medial frontal/anterior cingulate networks ( r  = -0.35, p  = 0.02). Our findings provide further evidence that BQ chewing may lead to brain functional connectivity changes, which may play a key role in the psychological and physiological effects of BQ.

  8. Weak Higher-Order Interactions in Macroscopic Functional Networks of the Resting Brain.

    PubMed

    Huang, Xuhui; Xu, Kaibin; Chu, Congying; Jiang, Tianzi; Yu, Shan

    2017-10-25

    Interactions among different brain regions are usually examined through functional connectivity (FC) analysis, which is exclusively based on measuring pairwise correlations in activities. However, interactions beyond the pairwise level, that is, higher-order interactions (HOIs), are vital in understanding the behavior of many complex systems. So far, whether HOIs exist among brain regions and how they can affect the brain's activities remains largely elusive. To address these issues, here, we analyzed blood oxygenation level-dependent (BOLD) signals recorded from six typical macroscopic functional networks of the brain in 100 human subjects (46 males and 54 females) during the resting state. Through examining the binarized BOLD signals, we found that HOIs within and across individual networks were both very weak regardless of the network size, topology, degree of spatial proximity, spatial scales, and whether the global signal was regressed. To investigate the potential mechanisms underlying the weak HOIs, we analyzed the dynamics of a network model and also found that HOIs were generally weak within a wide range of key parameters provided that the overall dynamic feature of the model was similar to the empirical data and it was operating close to a linear fluctuation regime. Our results suggest that weak HOI may be a general property of brain's macroscopic functional networks, which implies the dominance of pairwise interactions in shaping brain activities at such a scale and warrants the validity of widely used pairwise-based FC approaches. SIGNIFICANCE STATEMENT To explain how activities of different brain areas are coordinated through interactions is essential to revealing the mechanisms underlying various brain functions. Traditionally, such an interaction structure is commonly studied using pairwise-based functional network analyses. It is unclear whether the interactions beyond the pairwise level (higher-order interactions or HOIs) play any role in this

  9. Driving and driven architectures of directed small-world human brain functional networks.

    PubMed

    Yan, Chaogan; He, Yong

    2011-01-01

    Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA) and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86) to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus) and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule). Further split-half analyses indicated that our results were highly reproducible between two independent subgroups. The

  10. Imaging functional and structural brain connectomics in attention-deficit/hyperactivity disorder.

    PubMed

    Cao, Miao; Shu, Ni; Cao, Qingjiu; Wang, Yufeng; He, Yong

    2014-12-01

    Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopment disorders in childhood. Clinically, the core symptoms of this disorder include inattention, hyperactivity, and impulsivity. Previous studies have documented that these behavior deficits in ADHD children are associated with not only regional brain abnormalities but also changes in functional and structural connectivity among regions. In the past several years, our understanding of how ADHD affects the brain's connectivity has been greatly advanced by mapping topological alterations of large-scale brain networks (i.e., connectomes) using noninvasive neurophysiological and neuroimaging techniques (e.g., electroencephalograph, functional MRI, and diffusion MRI) in combination with graph theoretical approaches. In this review, we summarize the recent progresses of functional and structural brain connectomics in ADHD, focusing on graphic analysis of large-scale brain systems. Convergent evidence suggests that children with ADHD had abnormal small-world properties in both functional and structural brain networks characterized by higher local clustering and lower global integrity, suggesting a disorder-related shift of network topology toward regular configurations. Moreover, ADHD children showed the redistribution of regional nodes and connectivity involving the default-mode, attention, and sensorimotor systems. Importantly, these ADHD-associated alterations significantly correlated with behavior disturbances (e.g., inattention and hyperactivity/impulsivity symptoms) and exhibited differential patterns between clinical subtypes. Together, these connectome-based studies highlight brain network dysfunction in ADHD, thus opening up a new window into our understanding of the pathophysiological mechanisms of this disorder. These works might also have important implications on the development of imaging-based biomarkers for clinical diagnosis and treatment evaluation in ADHD.

  11. Diagnosing Autism Spectrum Disorder through Brain Functional Magnetic Resonance Imaging

    DTIC Science & Technology

    2016-03-01

    Diagnosing Autism Spectrum Disorder through Brain Functional Magnetic Resonance Imaging THESIS MARCH 2016 Kyle A. Palko, Second Lieutenant, USAF AFIT...declared a work of the U.S. Government and is not subject to copyright protection in the United States. AFIT-ENC-MS-16-M-123 DIAGNOSING AUTISM SPECTRUM...PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT-ENC-MS-16-M-123 DIAGNOSING AUTISM SPECTRUM DISORDER THROUGH BRAIN FUNCTIONAL MAGNETIC RESONANCE IMAGING Kyle

  12. Regulation of brain insulin signaling: A new function for tau

    PubMed Central

    Gratuze, Maud; Planel, Emmanuel

    2017-01-01

    In this issue of JEM, Marciniak et al. (https://doi.org/10.1084/jem.20161731) identify a putative novel function of tau protein as a regulator of insulin signaling in the brain. They find that tau deletion impairs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzheimer’s disease, impairment of brain insulin signaling might occur via tau loss of function. PMID:28652305

  13. Regulation of brain insulin signaling: A new function for tau.

    PubMed

    Gratuze, Maud; Planel, Emmanuel

    2017-08-07

    In this issue of JEM, Marciniak et al. (https://doi.org/10.1084/jem.20161731) identify a putative novel function of tau protein as a regulator of insulin signaling in the brain. They find that tau deletion impairs hippocampal response to insulin through IRS-1 and PTEN dysregulation and suggest that, in Alzheimer's disease, impairment of brain insulin signaling might occur via tau loss of function. © 2017 Gratuze and Planel.

  14. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

    PubMed Central

    Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

    2017-01-01

    Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

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

    PubMed

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

    2015-11-01

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

  16. Do (epi)genetics impact the brain in functional neurologic disorders?

    PubMed

    Frodl, T

    2016-01-01

    Advances in neuropsychiatric research are supposed to lead to significant improvements in understanding functional neurologic disorders and their diagnosis. However, epigenetic and genetic research on conversion disorders and somatoform disorders is only at its start. This review demonstrates the current state within this field and tries to bridge a gap from what is known on gene-stress interactions in other psychiatric disorders like depression. The etiology of conversion disorders is hypothesized to be multifactorial. These considerations also suggest that potential etiologic factors lead to alterations in brain function, either episodically or chronically, eventually leading to structural brain changes. In particular, the knowledge of how the environment influences brain structure and function, e.g., via epigenetic regulation, may be interesting for future research in functional neurologic disorders. Reviewing the literature results in evidence that childhood adversities play a role in the development of functional neurologic disorders, whereby at present no reports exist about the interactive effect between childhood adversity and genetic factors or about the impact of epigenetics. © 2016 Elsevier B.V. All rights reserved.

  17. Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

    ERIC Educational Resources Information Center

    Sidtis, John J.

    2007-01-01

    Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

  18. Individual differences in personality traits reflect structural variance in specific brain regions.

    PubMed

    Gardini, Simona; Cloninger, C Robert; Venneri, Annalena

    2009-06-30

    Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

  19. In Situ Activation of Antigen-Specific CD8+ T Cells in the Presence of Antigen in Organotypic Brain Slices1

    PubMed Central

    Ling, Changying; Verbny, Yakov I.; Banks, Matthew I.; Sandor, Matyas; Fabry, Zsuzsanna

    2012-01-01

    The activation of Ag-specific T cells locally in the CNS could potentially contribute to the development of immune-mediated brain diseases. We addressed whether Ag-specific T cells could be stimulated in the CNS in the absence of peripheral lymphoid tissues by analyzing Ag-specific T cell responses in organotypic brain slice cultures. Organotypic brain slice cultures were established 1 h after intracerebral OVA Ag microinjection. We showed that when OVA-specific CD8+ T cells were added to Ag-containing brain slices, these cells became activated and migrated into the brain to the sites of their specific Ags. This activation of OVA-specific T cells was abrogated by the deletion of CD11c+ cells from the brain slices of the donor mice. These data suggest that brain-resident CD11c+ cells stimulate Ag-specific naive CD8+ T cells locally in the CNS and may contribute to immune responses in the brain. PMID:18523307

  20. Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.

    2014-03-01

    Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.

  1. Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy.

    PubMed

    Amidi, Ali; Hosseini, S M Hadi; Leemans, Alexander; Kesler, Shelli R; Agerbæk, Mads; Wu, Lisa M; Zachariae, Robert

    2017-12-01

    Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning. Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up. At follow-up, 22 participants had received cisplatin-based chemotherapy (CT) while 42 were in active surveillance (S). Brain structural networks were constructed for each participant, and network properties were investigated using graph theory and longitudinally compared across groups. Cognitive functioning was evaluated using standardized neuropsychological tests. All statistical tests were two-sided. Compared with the S group, the CT group demonstrated altered global and local brain network properties from baseline to follow-up as evidenced by decreases in important brain network properties such as small-worldness (P = .04), network clustering (P = .04), and local efficiency (P = .02). In the CT group, poorer overall cognitive performance was associated with decreased small-worldness (r = -0.46, P = .04) and local efficiency (r = -0.51, P = .02), and verbal fluency was associated with decreased local efficiency (r = -0.55, P = .008). Brain structural networks may be disrupted following treatment with cisplatin-based chemotherapy. Impaired brain networks may underlie poorer performance over time on both specific and nonspecific cognitive functions in patients undergoing chemotherapy. To the best of our knowledge, this is the first study to longitudinally investigate changes in structural brain networks in a cancer population, providing novel insights regarding the

  2. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    PubMed

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Brain Functional Changes before, during, and after Clinical Pain.

    PubMed

    Hu, X; Racek, A J; Bellile, E; Nascimento, T D; Bender, M C; Toback, R L; Burnett, D; Khatib, L; McMahan, R; Kovelman, I; Ellwood, R P; DaSilva, A F

    2018-05-01

    This study used an emerging brain imaging technique, functional near-infrared spectroscopy (fNIRS), to investigate functional brain activation and connectivity that modulates sometimes traumatic pain experience in a clinical setting. Hemodynamic responses were recorded at bilateral somatosensory (S1) and prefrontal cortices (PFCs) from 12 patients with dentin hypersensitivity in a dental chair before, during, and after clinical pain. Clinical dental pain was triggered with 20 consecutive descending cold stimulations (32° to 0°C) to the affected teeth. We used a partial least squares path modeling framework to link patients' clinical pain experience with recorded hemodynamic responses at sequential stages and baseline resting-state functional connectivity (RSFC). Hemodynamic responses at PFC/S1 were sequentially elicited by expectation, cold detection, and pain perception at a high-level coefficient (coefficients: 0.92, 0.98, and 0.99, P < 0.05). We found that the pain ratings were positively affected only at a moderate level of coefficients by such sequence of functional activation (coefficient: 0.52, P < 0.05) and the baseline PFC-S1 RSFC (coefficient: 0.59, P < 0.05). Furthermore, when the dental pain had finally subsided, the PFC increased its functional connection with the affected S1 orofacial region contralateral to the pain stimulus and, in contrast, decreased with the ipsilateral homuncular S1 regions ( P < 0.05). Our study indicated for the first time that patients' clinical pain experience in the dental chair can be predicted concomitantly by their baseline functional connectivity between S1 and PFC, as well as their sequence of ongoing hemodynamic responses. In addition, this linked cascade of events had immediate after-effects on the patients' brain connectivity, even when clinical pain had already ceased. Our findings offer a better understating of the ongoing impact of affective and sensory experience in the brain before, during, and after clinical

  4. Neuropsychological assessment of executive functions following pediatric traumatic brain injury.

    PubMed

    Gaines, K Drorit; Soper, Henry V

    2018-01-01

    Assessment of executive functions in the adult is best captured at the stage where full maturation of brain development occurs. Assessment of executive functions of children, however, is considerably more complicated. First, assessment of executive functioning in children represents a snapshot of these developing functions at a particular time linked stage, which may have implications for further development. Second, neuropsychological measures available to assess executive functions in children are limited in number and scope and may not be sensitive to the gradual developmental changes. The present article provides an overview of the salient neurodevelopmental stages of executive functioning and discusses the utilization of recently developed neuropsychological measures to assess these stages. Comments on clinical implications of these findings regarding Traumatic Brain Injury will be provided.

  5. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  6. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa.

    PubMed

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. The present results may be limited to the methods applied during preprocessing and network construction. We demonstrated anorexia nervosa-related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.

  7. When Neuroscience ‘Touches’ Architecture: From Hapticity to a Supramodal Functioning of the Human Brain

    PubMed Central

    Papale, Paolo; Chiesi, Leonardo; Rampinini, Alessandra C.; Pietrini, Pietro; Ricciardi, Emiliano

    2016-01-01

    In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting ‘neuro-architecture’ as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people–environment relationships, and even provide empirical foundations for a renewed evidence-based design theory. PMID:27375542

  8. On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification.

    PubMed

    Pläschke, Rachel N; Cieslik, Edna C; Müller, Veronika I; Hoffstaedter, Felix; Plachti, Anna; Varikuti, Deepthi P; Goosses, Mareike; Latz, Anne; Caspers, Svenja; Jockwitz, Christiane; Moebus, Susanne; Gruber, Oliver; Eickhoff, Claudia R; Reetz, Kathrin; Heller, Julia; Südmeyer, Martin; Mathys, Christian; Caspers, Julian; Grefkes, Christian; Kalenscher, Tobias; Langner, Robert; Eickhoff, Simon B

    2017-12-01

    Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc. © 2017

  9. Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

    Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

    2013-01-01

    This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

  10. Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

    PubMed

    Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

    2015-01-01

    Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

  11. Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function?

    PubMed

    Marie, Christine; Pedard, Martin; Quirié, Aurore; Tessier, Anne; Garnier, Philippe; Totoson, Perle; Demougeot, Céline

    2018-06-01

    Low cerebral levels of brain-derived neurotrophic factor (BDNF), which plays a critical role in many brain functions, have been implicated in neurodegenerative, neurological and psychiatric diseases. Thus, increasing BDNF levels in the brain is considered an attractive possibility for the prevention/treatment of various brain diseases. To date, BDNF-based therapies have largely focused on neurons. However, given the cross-talk between endothelial cells and neurons and recent evidence that BDNF expressed by the cerebral endothelium largely accounts for BDNF levels present in the brain, it is likely that BDNF-based therapies would be most effective if they also targeted the cerebral endothelium. In this review, we summarize the available knowledge about the biology and actions of BDNF derived from endothelial cells of the cerebral microvasculature and we emphasize the remaining gaps and shortcomings.

  12. Dynamic functional brain networks involved in simple visual discrimination learning.

    PubMed

    Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis

    2014-10-01

    Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity

    PubMed Central

    2016-01-01

    The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin- (SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin- (PV-) and vasoactive intestinal peptide- (VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning. PMID:27403348

  14. Brain basis of early parent–infant interactions: psychology, physiology, and in vivo functional neuroimaging studies

    PubMed Central

    Swain, James E.; Lorberbaum, Jeffrey P.; Kose, Samet; Strathearn, Lane

    2015-01-01

    Parenting behavior critically shapes human infants’ current and future behavior. The parent–infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others’ expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain’s more general circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID:17355399

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

    PubMed Central

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

    2015-01-01

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

  16. Effects of Soccer Heading on Brain Structure and Function

    PubMed Central

    Rodrigues, Ana Carolina; Lasmar, Rodrigo Pace; Caramelli, Paulo

    2016-01-01

    Soccer is the most popular sport in the world, with more than 265 million players worldwide, including professional and amateur ones. Soccer is unique in comparison to other sports, as it is the only sport in which participants purposely use their head to hit the ball. Heading is considered as an offensive or defensive move whereby the player’s unprotected head is used to deliberately impact the ball and direct it during play. A soccer player can be subjected to an average of 6–12 incidents of heading the ball per competitive game, where the ball reaches high velocities. Moreover, in practice sessions, heading training, which involves heading the ball repeatedly at low velocities, is common. Although the scientific community, as well as the media, has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The purpose of this study is to review the existing literature regarding the effects of soccer heading on brain structure and function. Only in the last years, some investigations have addressed the impact of heading on brain structure, by using neuroimaging techniques. Similarly, there have been some recent studies investigating biochemical markers of brain injury in soccer players. There is evidence of association between heading and abnormal brain structure, but the data are still preliminary. Also, some studies have suggested that subconcussive head impacts, as heading, could cause cognitive impairment, whereas others have not corroborated this finding. Questions persist as to whether or not heading is deleterious to cognitive functioning. Further studies, especially with longitudinal designs, are needed to clarify the clinical significance of heading as a cause of brain injury and to identify risk factors. Such investigations might contribute to the establishment of safety

  17. Changes in functional brain networks following sports-related concussion in adolescents.

    PubMed

    Virji-Babul, Naznin; Hilderman, Courtney G E; Makan, Nadia; Liu, Aiping; Smith-Forrester, Jenna; Franks, Chris; Wang, Z J

    2014-12-01

    Sports-related concussion is a major public health issue; however, little is known about the underlying changes in functional brain networks in adolescents following injury. Our aim was to use the tools from graph theory to evaluate the changes in brain network properties following concussion in adolescent athletes. We recorded resting state electroencephalography (EEG) in 33 healthy adolescent athletes and 9 adolescent athletes with a clinical diagnosis of subacute concussion. Graph theory analysis was applied to these data to evaluate changes in brain networks. Global and local metrics of the structural properties of the graph were calculated for each group and correlated with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores. Brain networks of both groups showed small-world topology with no statistically significant differences in the global metrics; however, significant differences were found in the local metrics. Specifically, in the concussed group, we noted: 1) increased values of betweenness and degree in frontal electrode sites corresponding to the (R) dorsolateral prefrontal cortex and the (R) inferior frontal gyrus and 2) decreased values of degree in the region corresponding to the (R) frontopolar prefrontal cortex. In addition, there was significant negative correlation between degree and hub value, with total symptom score at the electrode site corresponding to the (R) prefrontal cortex. This preliminary report in adolescent athletes shows for the first time that resting-state EEG combined with graph theoretical analysis may provide an objective method of evaluating changes in brain networks following concussion. This approach may be useful in identifying individuals at risk for future injury.

  18. A Role for REM Sleep in Recalibrating the Sensitivity of the Human Brain to Specific Emotions

    PubMed Central

    Gujar, Ninad; McDonald, Steven Andrew; Nishida, Masaki

    2011-01-01

    Although the impact of sleep on cognitive function is increasingly well established, the role of sleep in modulating affective brain processes remains largely uncharacterized. Using a face recognition task, here we demonstrate an amplified reactivity to anger and fear emotions across the day, without sleep. However, an intervening nap blocked and even reversed this negative emotional reactivity to anger and fear while conversely enhancing ratings of positive (happy) expressions. Most interestingly, only those subjects who obtained rapid eye movement (REM) sleep displayed this remodulation of affective reactivity for the latter 2 emotion categories. Together, these results suggest that the evaluation of specific human emotions is not static across a daytime waking interval, showing a progressive reactivity toward threat-related negative expressions. However, an episode of sleep can reverse this predisposition, with REM sleep depotentiating negative reactivity toward fearful expressions while concomitantly facilitating recognition and ratings of reward-relevant positive expressions. These findings support the view that sleep, and specifically REM neurophysiology, may represent an important factor governing the optimal homeostasis of emotional brain regulation. PMID:20421251

  19. Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase δ-knockout mice.

    PubMed

    Usuki, Takako; Takato, Tamae; Lu, Qiang; Sakai, Hiromichi; Bando, Kana; Kiyonari, Hiroshi; Sakane, Fumio

    2016-10-01

    Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we reported that the δ isozyme of DGK was abundantly expressed in the mouse brain. However, the functions of DGKδ in the brain are still unclear. Because conventional DGKδ-knockout (KO) mice die within 24h after birth, we have generated brain-specific conditional DGKδ-KO mice to circumvent the lethality. In the novel object recognition test, the number of contacts in the DGKδ-KO mice to novel and familiar objects was greatly increased compared to the control mice, indicating that the DGKδ-KO mice showed irrational contacts with objects such as compulsive checking. In the marble burying test, which is used for analyzing obsessive-compulsive disorder (OCD)-like phenotypes, the DGKδ-KO mice buried more marbles than the control mice. Additionally, these phenotypes were significantly alleviated by the administration of an OCD remedy, fluoxetine. These results indicate that the DGKδ-KO mice showed OCD-like behaviors. Moreover, the number of long axon/neurites increased in both DGKδ-KO primary cortical neurons and DGKδ-knockdown neuroblastoma Neuro-2a cells compared to control cells. Conversely, overexpression of DGKδ decreased the number of long axon/neurites of Neuro-2a cells. Taken together, these results strongly suggest that a deficiency of DGKδ induces OCD-like behavior through enhancing axon/neurite outgrowth. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Aberrant functional brain connectome in people with antisocial personality disorder

    PubMed Central

    Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

    2016-01-01

    Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016–0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD. PMID:27257047