The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

The dynamics of human cognition: Increasing global integration coupled with decreasing segregation found using iEEG.

PubMed

Cruzat, Josephine; Deco, Gustavo; Tauste-Campo, Adrià; Principe, Alessandro; Costa, Albert; Kringelbach, Morten L; Rocamora, Rodrigo

2018-05-15

Cognitive processing requires the ability to flexibly integrate and process information across large brain networks. How do brain networks dynamically reorganize to allow broad communication between many different brain regions in order to integrate information? We record neural activity from 12 epileptic patients using intracranial EEG while performing three cognitive tasks. We assess how the functional connectivity between different brain areas changes to facilitate communication across them. At the topological level, this facilitation is characterized by measures of integration and segregation. Across all patients, we found significant increases in integration and decreases in segregation during cognitive processing, especially in the gamma band (50-90 Hz). We also found higher levels of global synchronization and functional connectivity during task execution, again particularly in the gamma band. More importantly, functional connectivity modulations were not caused by changes in the level of the underlying oscillations. Instead, these modulations were caused by a rearrangement of the mutual synchronization between the different nodes as proposed by the "Communication Through Coherence" Theory. Copyright © 2018 Elsevier Inc. All rights reserved.

Disrupted functional connectome in antisocial personality disorder.

PubMed

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2017-08-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

Disrupted functional connectome in antisocial personality disorder

PubMed Central

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

2017-01-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

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

Neurodevelopment and executive function in autism.

PubMed

O'Hearn, Kirsten; Asato, Miya; Ordaz, Sarah; Luna, Beatriz

2008-01-01

Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.

An Attempt to Determine the Construct Validity of Measures Hypothesized to Represent an Orientation to Right, Left, or Integrated Hemispheric Brain Function for a Sample of Primary School Children.

ERIC Educational Resources Information Center

Dumbrower, Jule; And Others

1981-01-01

This study attempts to obtain evidence of the construct validity of pupil ability tests hypothesized to represent orientation to right, left, or integrated hemispheric function, and of teacher observation subscales intended to reveal behaviors in school setting that were hypothesized to portray preference for right or left brain function. (Author)

Integrating Retinoic Acid Signaling with Brain Function

ERIC Educational Resources Information Center

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

2009-01-01

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

From Hippocampus to Whole-Brain: The Role of Integrative Processing in Episodic Memory Retrieval

PubMed Central

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

2017-01-01

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. PMID:28112460

ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936.

PubMed

Lyall, Donald M; Lopez, Lorna M; Bastin, Mark E; Maniega, Susana Muñoz; Penke, Lars; Valdés Hernández, Maria del C; Royle, Natalie A; Starr, John M; Porteous, David J; Wardlaw, Joanna M; Deary, Ian J

2013-01-01

The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686-765, and for neuroimaging variables was N = 488-587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.

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

PubMed

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

2017-04-01

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

Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction.

PubMed

Zhu, Zude; Yang, Fengjun; Li, Dongning; Zhou, Lianjun; Liu, Ying; Zhang, Ying; Chen, Xuezhi

2017-01-01

While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC) and low cloze (LC) probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC) was found in several regions, especially the left middle frontal gyrus (MFG) and right inferior frontal gyrus (IFG), which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

78 FR 26642 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

..., Functional and Cognitive Neuroscience Integrated Review Group; Somatosensory and Chemosensory Systems Study..., [email protected] . Name of Committee: Integrative, Functional and Cognitive Neuroscience Integrated... personal privacy. Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group...

The Effects of Spaceflight on Neurocognitive Performance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, Rachael D.; Bloomberg, Jacob; Wood, Scott; Mason, Sara; Mulavara, Ajit; Kofman, Igor; De Dios, Yiri; Gadd, Nicole; Stepanyan, Vahagn; Szecsy, Darcy

2017-01-01

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. We found extensive changes in behavior, brain structure & brain function following 70 days of HDBR. Specific Aim: Aim 1-Identify changes in brain structure, function, and network integrity as a function of spaceflight and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

ERIC Educational Resources Information Center

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

A comparison of participation outcome measures and the International Classification of Functioning, Disability and Health Core Sets for traumatic brain injury.

PubMed

Chung, Pearl; Yun, Sarah Jin; Khan, Fary

2014-02-01

To compare the contents of participation outcome measures in traumatic brain injury with the International Classification of Functioning, Disability and Health (ICF) Core Sets for traumatic brain injury. A systematic search with an independent review process selected relevant articles to identify outcome measures in participation in traumatic brain injury. Instruments used in two or more studies were linked to the ICF categories, which identified categories in participation for comparison with the ICF Core Sets for traumatic brain injury. Selected articles (n = 101) identified participation instruments used in two or more studies (n = 9): Community Integration Questionnaire, Craig Handicap Assessment and Reporting Technique, Mayo-Portland Adaptability Inventory-4 Participation Index, Sydney Psychosocial Reintegration Scale Version-2, Participation Assessment with Recombined Tool-Objective, Community Integration Measure, Participation Objective Participation Subjective, Community Integration Questionnaire-2, and Quality of Community Integration Questionnaire. Each instrument was linked to 4-35 unique second-level ICF categories, of which 39-100% related to participation. Instruments addressed 86-100% and 50-100% of the participation categories in the Comprehensive and Brief ICF Core Sets for traumatic brain injury, respectively. Participation measures in traumatic brain injury were compared with the ICF Core Sets for traumatic brain injury. The ICF Core Sets for traumatic brain injury could contribute to the development and selection of participation measures.

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.

The role of psychosocial factors and psychiatric disorders in functional dyspepsia.

PubMed

Van Oudenhove, Lukas; Aziz, Qasim

2013-03-01

In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.

Functional integrity in children with anoxic brain injury from drowning.

PubMed

Ishaque, Mariam; Manning, Janessa H; Woolsey, Mary D; Franklin, Crystal G; Tullis, Elizabeth W; Beckmann, Christian F; Fox, Peter T

2017-10-01

Drowning is a leading cause of accidental injury and death in young children. Anoxic brain injury (ABI) is a common consequence of drowning and can cause severe neurological morbidity in survivors. Assessment of functional status and prognostication in drowning victims can be extremely challenging, both acutely and chronically. Structural neuroimaging modalities (CT and MRI) have been of limited clinical value. Here, we tested the utility of resting-state functional MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven children with chronic, spastic quadriplegia due to drowning-induced ABI were investigated. All were comatose immediately after the injury and gradually regained consciousness, but with varying ability to communicate their cognitive state. Eleven neurotypical children matched for age and gender formed the control group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were acquired at night during drug-aided sleep. Network integrity was quantified by independent components analysis (ICA), at both group- and per-subject levels. Functional-status assessments based on in-home observations were provided by families and caregivers. Motor ICNs were grossly compromised in ABI patients both group-wise and individually, concordant with their prominent motor deficits. Striking preservations of perceptual and cognitive ICNs were observed, and the degree of network preservation correlated (ρ = 0.74) with the per-subject functional status assessments. Collectively, our findings indicate that rs-fMRI has promise for assessing brain functional integrity in ABI and, potentially, in other disorders. Furthermore, our observations suggest that the severe motor deficits observed in this population can mask relatively intact perceptual and cognitive capabilities. Hum Brain Mapp 38:4813-4831, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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

2006-02-01

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

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics

PubMed Central

Hernandez, Leanna M; Rudie, Jeffrey D; Green, Shulamite A; Bookheimer, Susan; Dapretto, Mirella

2015-01-01

Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data. PMID:25011468

Segregated Systems of Human Brain Networks.

PubMed

Wig, Gagan S

2017-12-01

The organization of the brain network enables its function. Evaluation of this organization has revealed that large-scale brain networks consist of multiple segregated subnetworks of interacting brain areas. Descriptions of resting-state network architecture have provided clues for understanding the functional significance of these segregated subnetworks, many of which correspond to distinct brain systems. The present report synthesizes accumulating evidence to reveal how maintaining segregated brain systems renders the human brain network functionally specialized, adaptable to task demands, and largely resilient following focal brain damage. The organizational properties that support system segregation are harmonious with the properties that promote integration across the network, but confer unique and important features to the brain network that are central to its function and behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Finding influential nodes for integration in brain networks using optimal percolation theory.

PubMed

Del Ferraro, Gino; Moreno, Andrea; Min, Byungjoon; Morone, Flaviano; Pérez-Ramírez, Úrsula; Pérez-Cervera, Laura; Parra, Lucas C; Holodny, Andrei; Canals, Santiago; Makse, Hernán A

2018-06-11

Global integration of information in the brain results from complex interactions of segregated brain networks. Identifying the most influential neuronal populations that efficiently bind these networks is a fundamental problem of systems neuroscience. Here, we apply optimal percolation theory and pharmacogenetic interventions in vivo to predict and subsequently target nodes that are essential for global integration of a memory network in rodents. The theory predicts that integration in the memory network is mediated by a set of low-degree nodes located in the nucleus accumbens. This result is confirmed with pharmacogenetic inactivation of the nucleus accumbens, which eliminates the formation of the memory network, while inactivations of other brain areas leave the network intact. Thus, optimal percolation theory predicts essential nodes in brain networks. This could be used to identify targets of interventions to modulate brain function.

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2017-11-01

Integration Theory of intelligence (Jung and Haier, Behave Brain Sci, 2007...predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are heritable and highly sensitive to both normal and...pathological aging processes. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity

Compensatory Motor Network Connectivity is Associated with Motor Sequence Learning after Subcortical Stroke

PubMed Central

Wadden, Katie P.; Woodward, Todd S.; Metzak, Paul D.; Lavigne, Katie M.; Lakhani, Bimal; Auriat, Angela M.; Boyd, Lara A.

2015-01-01

Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behaviour within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke. PMID:25757996

Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

PubMed

Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

2017-04-01

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex

PubMed Central

Lord, Anton R.; Li, Meng; Demenescu, Liliana R.; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

2017-01-01

The brain's connectivity skeleton—a rich club of strongly interconnected members—was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the “rich club.” Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age (p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC (p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level. PMID:28439224

Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex.

PubMed

Lord, Anton R; Li, Meng; Demenescu, Liliana R; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

2017-01-01

The brain's connectivity skeleton-a rich club of strongly interconnected members-was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the "rich club." Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age ( p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC ( p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level.

Determination of Death: A Scientific Perspective on Biological Integration

PubMed Central

Condic, Maureen L.

2016-01-01

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning.

PubMed

Faber, J; Wilde, E A; Hanten, G; Ewing-Cobbs, L; Aitken, M E; Yallampalli, R; MacLeod, M C; Mullins, S H; Chu, Z D; Li, X; Hunter, J V; Noble-Haeusslein, L; Levin, H S

2016-01-01

The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

PubMed

Tyler, Lorraine K; Wright, Paul; Randall, Billi; Marslen-Wilson, William D; Stamatakis, Emmanuel A

2010-11-01

The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory

PubMed Central

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

2014-01-01

With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model) or global dynamics (e.g., the Ising model) have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions. PMID:25276772

Effective connectivity inferred from fMRI transition dynamics during movie viewing points to a balanced reconfiguration of cortical interactions.

PubMed

Gilson, Matthieu; Deco, Gustavo; Friston, Karl J; Hagmann, Patric; Mantini, Dante; Betti, Viviana; Romani, Gian Luca; Corbetta, Maurizio

2017-10-09

Our behavior entails a flexible and context-sensitive interplay between brain areas to integrate information according to goal-directed requirements. However, the neural mechanisms governing the entrainment of functionally specialized brain areas remain poorly understood. In particular, the question arises whether observed changes in the regional activity for different cognitive conditions are explained by modifications of the inputs to the brain or its connectivity? We observe that transitions of fMRI activity between areas convey information about the tasks performed by 19 subjects, watching a movie versus a black screen (rest). We use a model-based framework that explains this spatiotemporal functional connectivity pattern by the local variability for 66 cortical regions and the network effective connectivity between them. We find that, among the estimated model parameters, movie viewing affects to a larger extent the local activity, which we interpret as extrinsic changes related to the increased stimulus load. However, detailed changes in the effective connectivity preserve a balance in the propagating activity and select specific pathways such that high-level brain regions integrate visual and auditory information, in particular boosting the communication between the two brain hemispheres. These findings speak to a dynamic coordination underlying the functional integration in the brain. Copyright © 2017. Published by Elsevier Inc.

Tracking the development of brain connectivity in adolescence through a fast Bayesian integrative method

NASA Astrophysics Data System (ADS)

Zhang, Aiying; Jia, Bochao; Wang, Yu-Ping

2018-03-01

Adolescence is a transitional period between childhood and adulthood with physical changes, as well as increasing emotional activity. Studies have shown that the emotional sensitivity is related to a second dramatical brain growth. However, there is little focus on the trend of brain development during this period. In this paper, we aim to track the functional brain connectivity development in adolescence using resting state fMRI (rs-fMRI), which amounts to a time-series analysis problem. Most existing methods either require the time point to be fairly long or are only applicable to small graphs. To this end, we adapted a fast Bayesian integrative analysis (FBIA) to address the short time-series difficulty, and combined with adaptive sum of powered score (aSPU) test for group difference. The data we used are the resting state fMRI (rs-fMRI) obtained from the publicly available Philadelphia Neurodevelopmental Cohort (PNC). They include 861 individuals aged 8-22 years who were divided into five different adolescent stages. We summarized the networks with global measurements: segregation and integration, and provided full brain functional connectivity pattern in various stages of adolescence. Moreover, our research revealed several brain functional modules development trends. Our results are shown to be both statistically and biologically significant.

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.

Realistic modeling of neurons and networks: towards brain simulation.

PubMed

D'Angelo, Egidio; Solinas, Sergio; Garrido, Jesus; Casellato, Claudia; Pedrocchi, Alessandra; Mapelli, Jonathan; Gandolfi, Daniela; Prestori, Francesca

2013-01-01

Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field.

Realistic modeling of neurons and networks: towards brain simulation

PubMed Central

D’Angelo, Egidio; Solinas, Sergio; Garrido, Jesus; Casellato, Claudia; Pedrocchi, Alessandra; Mapelli, Jonathan; Gandolfi, Daniela; Prestori, Francesca

Summary Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field. PMID:24139652

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

Successful tactile based visual sensory substitution use functions independently of visual pathway integrity

PubMed Central

Lee, Vincent K.; Nau, Amy C.; Laymon, Charles; Chan, Kevin C.; Rosario, Bedda L.; Fisher, Chris

2014-01-01

Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ≤ 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort. Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients. PMID:24860473

Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species

NASA Astrophysics Data System (ADS)

Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook; Kim, Minkyung; Iturria-Medina, Yasser; Choi, Jee-Hyun; Lee, Joseph; Mashour, George A.; Lee, Uncheol

2017-04-01

Identifying how spatially distributed information becomes integrated in the brain is essential to understanding higher cognitive functions. Previous computational and empirical studies suggest a significant influence of brain network structure on brain network function. However, there have been few analytical approaches to explain the role of network structure in shaping regional activities and directionality patterns. In this study, analytical methods are applied to a coupled oscillator model implemented in inhomogeneous networks. We first derive a mathematical principle that explains the emergence of directionality from the underlying brain network structure. We then apply the analytical methods to the anatomical brain networks of human, macaque, and mouse, successfully predicting simulation and empirical electroencephalographic data. The results demonstrate that the global directionality patterns in resting state brain networks can be predicted solely by their unique network structures. This study forms a foundation for a more comprehensive understanding of how neural information is directed and integrated in complex brain networks.

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

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

PubMed Central

Madden, David J.; Bennett, Ilana J.; Song, Allen W.

2009-01-01

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior-posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application. PMID:19705281

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

PubMed

Modarres, Hassan Pezeshgi; Janmaleki, Mohsen; Novin, Mana; Saliba, John; El-Hajj, Fatima; RezayatiCharan, Mahdi; Seyfoori, Amir; Sadabadi, Hamid; Vandal, Milène; Nguyen, Minh Dang; Hasan, Anwarul; Sanati-Nezhad, Amir

2018-03-10

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain-based treatment-A new approach or a well-forgotten old one?

PubMed

Matanova, Vanya; Kostova, Zlatomira; Kolev, Martin

2018-04-24

For a relatively long period of time, mental functioning was mainly associated with personal profile while brain functioning went by the wayside. After the 90s of the 20th century, or the so called "Decade of the Brain", today, contemporary specialists work on the boundary between fundamental science and medicine. This brings neuroscience, neuropsychology, psychiatry, and psychotherapy closer to each other. Today, we definitely know that brain structures are being built and altered thanks to experience. Psychotherapy can be more effective when based on a neuropsychological approach-this implies identification of the neural foundations of various disorders and will lead to specific psychotherapeutic conclusions. The knowledge about the brain is continually enriched, which leads to periodic rethinking and updating of the therapeutic approaches to various diseases of the nervous system and brain dysfunctions. The aim of translational studies is to match and combine scientific areas, resources, experience and techniques to improve prevention, diagnosis and therapies, and "transformation" of scientific discoveries into potential treatments of various diseases done in laboratory conditions. Neuropsychological studies prove that cognition is a key element that links together brain functioning and behaviour. According to Dr. Kandel, all experimental events, including psychotherapeutic interventions, affect the structure and function of neuronal synapses. The story of why psychotherapy works is a story of understanding the brain mechanisms of psychic processes, a story of how the brain has been evolving to ensure learning, forgetting, and the mechanisms of permanent psychological change. The new evidence on brain functioning necessitates the integration of neuropsychological achievements in the psychotherapeutic process. An integrative approach is needed to take into account the dynamic interaction between brain functioning, psyche, soul, spirit, and social interaction, ie, development of a model of psychotherapeutic work based on cerebral plasticity! Brain-based psychotherapy aims at changing brain functioning not directly, but through experiences. This is neuro-psychologically informed psychotherapy. © 2018 John Wiley & Sons, Ltd.

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.

Assessing Children with Traumatic Brain Injuries: Integrating Educational and Medical Issues.

ERIC Educational Resources Information Center

Shaw, Steven R.; Yingst, Christine A.

1992-01-01

This overview of traumatic brain injuries discusses (1) incidence and prevalence; (2) characteristics; (3) the recovery process; and (4) educational/medical assessment, including premorbid functioning, current functioning, educationally relevant medical issues, and amount and type of family support. (JDD)

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Differences in Brain Structure and Function in Older Adults with Self-Reported Disabling and Non-Disabling Chronic Low Back Pain

PubMed Central

Buckalew, Neilly; Haut, Marc W.; Aizenstein, Howard; Morrow, Lisa; Perera, Subashan; Kuwabara, Hiroto; Weiner, Debra K.

2010-01-01

Objective The primary aim of this pilot study was to identify structural and functional brain differences in older adults with self-reported disabling chronic low back pain (CLBP) compared with those who reported non-disabling CLBP. Design Cross-sectional. Participants Sixteen cognitively intact older adults, eight with disabling CLBP and eight with non-disabling. Exclusions were psychiatric or neurological disorders, substance abuse, opioid use, or diabetes mellitus. Methods Participants underwent: structural and functional brain MRI; neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Tests A and B; and physical performance assessment using the Short Physical Performance Battery. Results In the disabled group there was significantly lower white matter (WM) integrity (P < 0.05) of the splenium of the corpus callosum. This group also demonstrated activation of the right medial prefrontal cortex at rest whereas the non-disabled demonstrated activation of the left lateral prefrontal cortex. Combined groups analysis revealed a strong positive correlation (rs = 0.80, P < 0.0002) between WM integrity of the left centrum semiovale with gait-speed. Secondary analysis revealed a strong negative correlation between total months of CLBP and WM integrity of the SCC (rs = −0.59, P < 0.02). Conclusions Brain structure and function is different in older adults with disabling CLBP compared to those with non-disabling CLBP. Deficits in brain morphology combining groups are associated with pain duration and poor physical function. Our findings suggest brain structure and function may play a key role in chronic-pain-related-disability and may be important treatment targets. PMID:20609128

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

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

The Exercising Brain: Changes in Functional Connectivity Induced by an Integrated Multimodal Cognitive and Whole-Body Coordination Training

PubMed Central

Demirakca, Traute; Cardinale, Vita; Dehn, Sven; Ruf, Matthias; Ende, Gabriele

2016-01-01

This study investigated the impact of “life kinetik” training on brain plasticity in terms of an increased functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI). The training is an integrated multimodal training that combines motor and cognitive aspects and challenges the brain by introducing new and unfamiliar coordinative tasks. Twenty-one subjects completed at least 11 one-hour-per-week “life kinetik” training sessions in 13 weeks as well as before and after rs-fMRI scans. Additionally, 11 control subjects with 2 rs-fMRI scans were included. The CONN toolbox was used to conduct several seed-to-voxel analyses. We searched for functional connectivity increases between brain regions expected to be involved in the exercises. Connections to brain regions representing parts of the default mode network, such as medial frontal cortex and posterior cingulate cortex, did not change. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected. We can conclude that the constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory demands, seems to induce brain plasticity expressed in enhanced connectivity strength of brain regions due to coactivation. PMID:26819776

Brainstem death: A comprehensive review in Indian perspective

PubMed Central

Dhanwate, Anant Dattatray

2014-01-01

With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India. PMID:25249744

The Metastable Brain

PubMed Central

Tognoli, Emmanuelle; Kelso, J. A. Scott

2014-01-01

Neural ensembles oscillate across a broad range of frequencies and are transiently coupled or “bound” together when people attend to a stimulus, perceive, think and act. This is a dynamic, self-assembling process, with parts of the brain engaging and disengaging in time. But how is it done? The theory of Coordination Dynamics proposes a mechanism called metastability, a subtle blend of integration and segregation. Tendencies for brain regions to express their individual autonomy and specialized functions (segregation, modularity) coexist with tendencies to couple and coordinate globally for multiple functions (integration). Although metastability has garnered increasing attention, it has yet to be demonstrated and treated within a fully spatiotemporal perspective. Here, we illustrate metastability in continuous neural and behavioral recordings, and we discuss theory and experiments at multiple scales suggesting that metastable dynamics underlie the real-time coordination necessary for the brain's dynamic cognitive, behavioral and social functions. PMID:24411730

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.

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

PubMed

Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

2010-10-01

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

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

PubMed

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

2016-05-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

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

Organization and hierarchy of the human functional brain network lead to a chain-like core.

PubMed

Mastrandrea, Rossana; Gabrielli, Andrea; Piras, Fabrizio; Spalletta, Gianfranco; Caldarelli, Guido; Gili, Tommaso

2017-07-07

The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.

Correlated gene expression and anatomical communication support synchronized brain activity in the mouse functional connectome.

PubMed

Mills, Brian D; Grayson, David S; Shunmugavel, Anandakumar; Miranda-Dominguez, Oscar; Feczko, Eric; Earl, Eric; Neve, Kim; Fair, Damien A

2018-05-22

Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI. SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still largely unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be utilized to streamline preclinical animal studies of disease. Copyright © 2018 the authors.

A Network Model of the Emotional Brain.

PubMed

Pessoa, Luiz

2017-05-01

Emotion is often understood in terms of a circumscribed set of cortical and subcortical brain regions. I propose, instead, that emotion should be understood in terms of large-scale network interactions spanning the entire neuroaxis. I describe multiple anatomical and functional principles of brain organization that lead to the concept of 'functionally integrated systems', cortical-subcortical systems that anchor the organization of emotion in the brain. The proposal is illustrated by describing the cortex-amygdala integrated system and how it intersects with systems involving the ventral striatum/accumbens, septum, hippocampus, hypothalamus, and brainstem. The important role of the thalamus is also highlighted. Overall, the model clarifies why the impact of emotion is wide-ranging, and how emotion is interlocked with perception, cognition, motivation, and action. Copyright © 2017 Elsevier Ltd. All rights reserved.

Network neuroscience

PubMed Central

Bassett, Danielle S; Sporns, Olaf

2017-01-01

Despite substantial recent progress, our understanding of the principles and mechanisms underlying complex brain function and cognition remains incomplete. Network neuroscience proposes to tackle these enduring challenges. Approaching brain structure and function from an explicitly integrative perspective, network neuroscience pursues new ways to map, record, analyze and model the elements and interactions of neurobiological systems. Two parallel trends drive the approach: the availability of new empirical tools to create comprehensive maps and record dynamic patterns among molecules, neurons, brain areas and social systems; and the theoretical framework and computational tools of modern network science. The convergence of empirical and computational advances opens new frontiers of scientific inquiry, including network dynamics, manipulation and control of brain networks, and integration of network processes across spatiotemporal domains. We review emerging trends in network neuroscience and attempt to chart a path toward a better understanding of the brain as a multiscale networked system. PMID:28230844

The Holographic Brain: Implications for Training Design.

ERIC Educational Resources Information Center

Jones, James R.

Without special training, most people predominantly process data in one of four ways. Few achieve a coveted whole brain state that integrates such important but separate brain functions as logic and intuition. With new training techniques that exploit the holographic properties of the brain, organizations may be able to tap powerful whole brain…

Adolescent Emotional Maturation through Divergent Models of Brain Organization

PubMed Central

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

2016-01-01

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

Speed of perceptual grouping in acquired brain injury.

PubMed

Kurylo, Daniel D; Larkin, Gabriella Brick; Waxman, Richard; Bukhari, Farhan

2014-09-01

Evidence exists that damage to white matter connections may contribute to reduced speed of information processing in traumatic brain injury and stroke. Damage to such axonal projections suggests a particular vulnerability to functions requiring integration across cortical sites. To test this prediction, measurements were made of perceptual grouping, which requires integration of stimulus components. A group of traumatic brain injury and cerebral vascular accident patients and a group of age-matched healthy control subjects viewed arrays of dots and indicated the pattern into which stimuli were perceptually grouped. Psychophysical measurements were made of perceptual grouping as well as processing speed. The patient group showed elevated grouping thresholds as well as extended processing time. In addition, most patients showed progressive slowing of processing speed across levels of difficulty, suggesting reduced resources to accommodate increased demands on grouping. These results support the prediction that brain injury results in a particular vulnerability to functions requiring integration of information across the cortex, which may result from dysfunction of long-range axonal connection.

MRIVIEW: An interactive computational tool for investigation of brain structure and function

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

Ranken, D.; George, J.

MRIVIEW is a software system which uses image processing and visualization to provide neuroscience researchers with an integrated environment for combining functional and anatomical information. Key features of the software include semi-automated segmentation of volumetric head data and an interactive coordinate reconciliation method which utilizes surface visualization. The current system is a precursor to a computational brain atlas. We describe features this atlas will incorporate, including methods under development for visualizing brain functional data obtained from several different research modalities.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Anterior Temporal Lobe Connectivity Correlates with Functional Outcome after Aphasic Stroke

ERIC Educational Resources Information Center

Warren, Jane E.; Crinion, Jennifer T.; Ralph, Matthew A. Lambon; Wise, Richard J. S.

2009-01-01

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic…

Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes

PubMed Central

Motch Perrine, Susan M.; Stecko, Tim; Neuberger, Thomas; Jabs, Ethylin W.; Ryan, Timothy M.; Richtsmeier, Joan T.

2017-01-01

The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology. Using mouse models for craniosynostosis conditions, our group has precisely defined how unique craniosynostosis causing mutations in fibroblast growth factor receptors affect brain and skull morphology and dysgenesis involving coordinated tissue-specific effects of these mutations. Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2 S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases. Using linear distances estimated from three-dimensional coordinates of landmarks acquired from dual modality imaging of skull (high resolution micro-computed tomography and magnetic resonance microscopy) of mice at embryonic day 17.5, we confirm variation in brain and skull morphology in Fgfr2cC342Y/+ mice, Fgfr2+/S252W mice, and their unaffected littermates. Mutation-specific variation in neural and cranial tissue notwithstanding, patterns of integration of brain and skull differed only subtly between mice carrying either the FGFR2c C342Y or the FGFR2 S252W mutation and their unaffected littermates. However, statistically significant and substantial differences in morphological integration of brain and skull were revealed between the two mutant mouse models, each maintained on a different strain. Relative to the effects of disease-associated mutations, our results reveal a stronger influence of the background genome on patterns of brain-skull integration and suggest robust genetic, developmental, and evolutionary relationships between neural and skeletal tissues of the head. PMID:28790902

The functional significance of newly born neurons integrated into olfactory bulb circuits.

PubMed

Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

2014-01-01

The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

The functional significance of newly born neurons integrated into olfactory bulb circuits

PubMed Central

Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

2014-01-01

The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons. PMID:24904263

Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.

PubMed

Nikolian, Vahagn C; Dekker, Simone E; Bambakidis, Ted; Higgins, Gerald A; Dennahy, Isabel S; Georgoff, Patrick E; Williams, Aaron M; Andjelkovic, Anuska V; Alam, Hasan B

2018-01-01

Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation. Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis). Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg). Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation. Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling. Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.

Evaluating the functional state of adult-born neurons in the adult dentate gyrus of the hippocampus: from birth to functional integration.

PubMed

Aguilar-Arredondo, Andrea; Arias, Clorinda; Zepeda, Angélica

2015-01-01

Hippocampal neurogenesis occurs in the adult brain in various species, including humans. A compelling question that arose when neurogenesis was accepted to occur in the adult dentate gyrus (DG) is whether new neurons become functionally relevant over time, which is key for interpreting their potential contributions to synaptic circuitry. The functional state of adult-born neurons has been evaluated using various methodological approaches, which have, in turn, yielded seemingly conflicting results regarding the timing of maturation and functional integration. Here, we review the contributions of different methodological approaches to addressing the maturation process of adult-born neurons and their functional state, discussing the contributions and limitations of each method. We aim to provide a framework for interpreting results based on the approaches currently used in neuroscience for evaluating functional integration. As shown by the experimental evidence, adult-born neurons are prone to respond from early stages, even when they are not yet fully integrated into circuits. The ongoing integration process for the newborn neurons is characterised by different features. However, they may contribute differently to the network depending on their maturation stage. When combined, the strategies used to date convey a comprehensive view of the functional development of newly born neurons while providing a framework for approaching the critical time at which new neurons become functionally integrated and influence brain function.

Plasticity of brain wave network interactions and evolution across physiologic states

PubMed Central

Liu, Kang K. L.; Bartsch, Ronny P.; Lin, Aijing; Mantegna, Rosario N.; Ivanov, Plamen Ch.

2015-01-01

Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of network connectivity and link strength, while at the same time each frequency-specific network is characterized by a different signature pattern of sleep-stage stratification, reflecting a remarkable flexibility in response to change in physiologic state. These new aspects of neural plasticity demonstrate that in addition to dominant brain waves, the network of brain wave interactions is a previously unrecognized hallmark of physiologic state and function. PMID:26578891

Prenatal Exposure of Guinea Pigs to the Organophosphorus Pesticide Chlorpyrifos Disrupts the Structural and Functional Integrity of the Brain

PubMed Central

Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Pescrille, Joseph D.; Todd, Spencer W.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

2015-01-01

This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (20 mg/kg, s.c.) or vehicle (peanut oil) once per day for ten consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris Water Maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T2-weighted anatomical scans and Diffusion Kurtosis Imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of pre-natal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. PMID:25704171

Brain Connectivity and Visual Attention

PubMed Central

Parks, Emily L.

2013-01-01

Abstract Emerging hypotheses suggest that efficient cognitive functioning requires the integration of separate, but interconnected cortical networks in the brain. Although task-related measures of brain activity suggest that a frontoparietal network is associated with the control of attention, little is known regarding how components within this distributed network act together or with other networks to achieve various attentional functions. This review considers both functional and structural studies of brain connectivity, as complemented by behavioral and task-related neuroimaging data. These studies show converging results: The frontal and parietal cortical regions are active together, over time, and identifiable frontoparietal networks are active in relation to specific task demands. However, the spontaneous, low-frequency fluctuations of brain activity that occur in the resting state, without specific task demands, also exhibit patterns of connectivity that closely resemble the task-related, frontoparietal attention networks. Both task-related and resting-state networks exhibit consistent relations to behavioral measures of attention. Further, anatomical structure, particularly white matter pathways as defined by diffusion tensor imaging, places constraints on intrinsic functional connectivity. Lastly, connectivity analyses applied to investigate cognitive differences across individuals in both healthy and diseased states suggest that disconnection of attentional networks is linked to deficits in cognitive functioning, and in extreme cases, to disorders of attention. Thus, comprehensive theories of visual attention and their clinical translation depend on the continued integration of behavioral, task-related neuroimaging, and brain connectivity measures. PMID:23597177

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

Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

PubMed

Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

2016-05-01

Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

Higher levels of trait emotional awareness are associated with more efficient global information integration throughout the brain: A graph-theoretic analysis of resting state functional connectivity.

PubMed

Smith, Ryan; Sanova, Anna; Alkozei, Anna; Lane, Richard D; Killgore, William D S

2018-06-21

Previous studies have suggested that trait differences in emotional awareness (tEA) are clinically relevant, and associated with differences in neural structure/function. While multiple leading theories suggest that conscious awareness requires widespread information integration across the brain, no study has yet tested the hypothesis that higher tEA corresponds to more efficient brain-wide information exchange. Twenty-six healthy volunteers (13 female) underwent a resting state functional magnetic resonance imaging scan, and completed the Levels of Emotional Awareness Scale (LEAS; a measure of tEA) and the Wechsler Abbreviated Scale of Intelligence (WASI-II; a measure of general intelligence [IQ]). Using a whole-brain (functionally defined) region-of-interest (ROI) atlas, we computed several graph theory metrics to assess the efficiency of brain-wide information exchange. After statistically controlling for differences in age, gender, and IQ, we first observed a significant relationship between higher LEAS scores and greater average degree (i.e., overall whole-brain network density). When controlling for average degree, we found that higher LEAS scores were also associated with shorter average path lengths across the collective network of all included ROIs. These results jointly suggest that individuals with higher tEA display more efficient global information exchange throughout the brain. This is consistent with the idea that conscious awareness requires global accessibility of represented information.

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.

Topological Alterations of the Intrinsic Brain Network in Patients with Functional Dyspepsia.

PubMed

Nan, Jiaofen; Zhang, Li; Zhu, Fubao; Tian, Xiaorui; Zheng, Qian; Deneen, Karen M von; Liu, Jixin; Zhang, Ming

2016-01-31

Previous studies reported that integrated information in the brain ultimately determines the subjective experience of patients with chronic pain, but how the information is integrated in the brain connectome of functional dyspepsia (FD) patients remains largely unclear. The study aimed to quantify the topological changes of the brain network in FD patients. Small-world properties, network efficiency and nodal centrality were utilized to measure the changes in topological architecture in 25 FD patients and 25 healthy controls based on functional magnetic resonance imaging. Pearson's correlation assessed the relationship of each topological property with clinical symptoms. FD patients showed an increase of clustering coefficients and local efficiency relative to controls from the perspective of a whole network as well as elevated nodal centrality in the right orbital part of the inferior frontal gyrus, left anterior cingulate gyrus and left hippocampus, and decreased nodal centrality in the right posterior cingulate gyrus, left cuneus, right putamen, left middle occipital gyrus and right inferior occipital gyrus. Moreover, the centrality in the anterior cingulate gyrus was significantly associated with symptom severity and duration in FD patients. Nevertheless, the inclusion of anxiety and depression scores as covariates erased the group differences in nodal centralities in the orbital part of the inferior frontal gyrus and hippocampus. The results suggest topological disruption of the functional brain networks in FD patients, presumably in response to disturbances of sensory information integrated with emotion, memory, pain modulation, and selective attention in patients.

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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 Wiley Periodicals, Inc.

Recent developments of functional magnetic resonance imaging research for drug development in Alzheimer's disease.

PubMed

Hampel, Harald; Prvulovic, David; Teipel, Stefan J; Bokde, Arun L W

2011-12-01

The objective of this review is to evaluate recent advances in functional magnetic resonance imaging (fMRI) research in Alzheimer's disease for the development of therapeutic agents. The basic building block underpinning cognition is a brain network. The measured brain activity serves as an integrator of the various components, from genes to structural integrity, that impact the function of networks underpinning cognition. Specific networks can be interrogated using cognitive paradigms such as a learning task or a working memory task. In addition, recent advances in our understanding of neural networks allow one to investigate the function of a brain network by investigating the inherent coherency of the brain networks that can be measured during resting state. The coherent resting state networks allow testing in cognitively impaired patients that may not be possible with the use of cognitive paradigms. In particular the default mode network (DMN) includes the medial temporal lobe and posterior cingulate, two key regions that support episodic memory function and are impaired in the earliest stages of Alzheimer's disease (AD). By investigating the effects of a prospective drug compound on this network, it could illuminate the specificity of the compound with a network supporting memory function. This could provide valuable information on the methods of action at physiological and behaviourally relevant levels. Utilizing fMRI opens up new areas of research and a new approach for drug development, as it is an integrative tool to investigate entire networks within the brain. The network based approach provides a new independent method from previous ones to translate preclinical knowledge into the clinical domain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neurocognitive mechanisms of mathematical giftedness: A literature review.

PubMed

Zhang, Li; Gan, John Q; Wang, Haixian

2017-01-01

Mathematically gifted children/adolescents have demonstrated exceptional abilities and traits in logical reasoning, mental imagery, and creative thinking. In the field of cognitive neuroscience, the past studies on mathematically gifted brains have concentrated on investigating event-related brain activation regions, cerebral laterality of cognitive functions, functional specialization that is uniquely dedicated for specific cognitive purposes, and functional interactions among discrete brain regions. From structural and functional perspectives, these studies have witnessed both "general" and "unique" neural characteristics of mathematically gifted brains. In this article, the theoretical background, empirical studies, and neurocognitive mechanisms of mathematically gifted children/adolescents are reviewed. Based on the integration of the findings, some potential directions for the future research are identified and discussed.

Neuronavigation in the surgical management of brain tumors: current and future trends

PubMed Central

Orringer, Daniel A; Golby, Alexandra; Jolesz, Ferenc

2013-01-01

Neuronavigation has become an ubiquitous tool in the surgical management of brain tumors. This review describes the use and limitations of current neuronavigational systems for brain tumor biopsy and resection. Methods for integrating intraoperative imaging into neuronavigational datasets developed to address the diminishing accuracy of positional information that occurs over the course of brain tumor resection are discussed. In addition, the process of integration of functional MRI and tractography into navigational models is reviewed. Finally, emerging concepts and future challenges relating to the development and implementation of experimental imaging technologies in the navigational environment are explored. PMID:23116076

Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

PubMed Central

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

2015-01-01

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

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

Human intelligence and brain networks

PubMed Central

Colom, Roberto; Karama, Sherif; Jung, Rex E.; Haier, Richard J.

2010-01-01

Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other. PMID:21319494

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

PubMed Central

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

2013-01-01

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

The Neurobiology of Alcohol Consumption and Alcoholism: An Integrative History1

PubMed Central

Tabakoff, Boris; Hoffman, Paula L.

2013-01-01

Studies of the neurobiological predisposition to consume alcohol (ethanol) and to transition to uncontrolled drinking behavior (alcoholism), as well as studies of the effects of alcohol on brain function, started a logarithmic growth phase after the repeal of the 18th Amendment to the United States Constitution. Although the early studies were primitive by current technological standards, they clearly demonstrated the effects of alcohol on brain structure and function, and by the end of the 20th century left little doubt that alcoholism is a “disease” of the brain. This review traces the history of developments in the understanding of ethanol’s effects on the most prominent inhibitory and excitatory systems of brain (GABA and glutamate neurotransmission). This neurobiological information is integrated with knowledge of ethanol’s actions on other neurotransmitter systems to produce an anatomical and functional map of ethanol’s properties. Our intent is limited in scope, but is meant to provide context and integration of the actions of ethanol on the major neurobiologic systems which produce reinforcement for alcohol consumption and changes in brain chemistry that lead to addiction. The developmental history of neurobehavioral theories of the transition from alcohol drinking to alcohol addiction is presented and juxtaposed to the neurobiological findings. Depending on one’s point of view, we may, at this point in history, know more, or less, than we think we know about the neurobiology of alcoholism. PMID:24141171

Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

PubMed

Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

2017-09-07

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

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

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

PubMed Central

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

2015-01-01

Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter (WM) damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1–5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using event-related potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy—a common sign of impaired WM—and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is the primary cause of death and disability in children and adolescents. There is considerable heterogeneity in postinjury outcome, which is only partially explained by injury severity. Imaging biomarkers may help explain some of this variance, as diffusion weighted imaging is sensitive to the white matter disruption that is common after injury. The corpus callosum (CC) is one of the most commonly reported areas of disruption. In this multimodal study, we discovered a divergence within our pediatric moderate-to-severe TBI sample 1–5 months postinjury. A subset of the TBI sample showed significant impairment in CC function, which is supported by additional results showing deficits in CC structural integrity. This subset also had poorer neurocognitive functioning. Our research sheds light on postinjury heterogeneity. PMID:26180196

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

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

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

The brain as a "hyper-network": the key role of neural networks as main producers of the integrated brain actions especially via the "broadcasted" neuroconnectomics.

PubMed

Agnati, Luigi F; Marcoli, Manuela; Maura, Guido; Woods, Amina; Guidolin, Diego

2018-06-01

Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the "core components" of the brain hyper-network that has as special "nodes" the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions.

The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging

PubMed Central

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

2013-01-01

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

The Virtual Mouse Brain: A Computational Neuroinformatics Platform to Study Whole Mouse Brain Dynamics.

PubMed

Melozzi, Francesca; Woodman, Marmaduke M; Jirsa, Viktor K; Bernard, Christophe

2017-01-01

Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain's structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain (TVB) to whole mouse brain network modeling based on individual diffusion magnetic resonance imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain (TVMB) to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. TVMB enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.

Toward Developmental Connectomics of the Human Brain

PubMed Central

Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

2016-01-01

Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders. PMID:27064378

The functional integration of the anterior cingulate cortex during conflict processing.

PubMed

Fan, Jin; Hof, Patrick R; Guise, Kevin G; Fossella, John A; Posner, Michael I

2008-04-01

Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.

The integrate model of emotion, thinking and self regulation: an application to the "paradox of aging".

PubMed

Williams, Leanne M; Gatt, Justine M; Hatch, Ainslie; Palmer, Donna M; Nagy, Marie; Rennie, Christopher; Cooper, Nicholas J; Morris, Charlotte; Grieve, Stuart; Dobson-Stone, Carol; Schofield, Peter; Clark, C Richard; Gordon, Evian; Arns, Martijn; Paul, Robert H

2008-09-01

This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.

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).

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

Verbal Neuropsychological Functions in Aphasia: An Integrative Model

ERIC Educational Resources Information Center

Vigliecca, Nora Silvana; Báez, Sandra

2015-01-01

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

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.

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

77 FR 54583 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... . Name of Committee: Integrative, Functional and Cognitive Neuroscience Integrated Review Group, Auditory... 20892, 301-402- 4411, [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience...

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

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

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.

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

Selective impairment of hippocampus and posterior hub areas in Alzheimer's disease: an MEG-based multiplex network study.

PubMed

Yu, Meichen; Engels, Marjolein M A; Hillebrand, Arjan; van Straaten, Elisabeth C W; Gouw, Alida A; Teunissen, Charlotte; van der Flier, Wiesje M; Scheltens, Philip; Stam, Cornelis J

2017-05-01

Although frequency-specific network analyses have shown that functional brain networks are altered in patients with Alzheimer's disease, the relationships between these frequency-specific network alterations remain largely unknown. Multiplex network analysis is a novel network approach to study complex systems consisting of subsystems with different types of connectivity patterns. In this study, we used magnetoencephalography to integrate five frequency-band specific brain networks in a multiplex framework. Previous structural and functional brain network studies have consistently shown that hub brain areas are selectively disrupted in Alzheimer's disease. Accordingly, we hypothesized that hub regions in the multiplex brain networks are selectively targeted in patients with Alzheimer's disease in comparison to healthy control subjects. Eyes-closed resting-state magnetoencephalography recordings from 27 patients with Alzheimer's disease (60.6 ± 5.4 years, 12 females) and 26 controls (61.8 ± 5.5 years, 14 females) were projected onto atlas-based regions of interest using beamforming. Subsequently, source-space time series for both 78 cortical and 12 subcortical regions were reconstructed in five frequency bands (delta, theta, alpha 1, alpha 2 and beta band). Multiplex brain networks were constructed by integrating frequency-specific magnetoencephalography networks. Functional connections between all pairs of regions of interests were quantified using a phase-based coupling metric, the phase lag index. Several multiplex hub and heterogeneity metrics were computed to capture both overall importance of each brain area and heterogeneity of the connectivity patterns across frequency-specific layers. Different nodal centrality metrics showed consistently that several hub regions, particularly left hippocampus, posterior parts of the default mode network and occipital regions, were vulnerable in patients with Alzheimer's disease compared to control subjects. Of note, these detected vulnerable hubs in Alzheimer's disease were absent in each individual frequency-specific network, thus showing the value of integrating the networks. The connectivity patterns of these vulnerable hub regions in the patients were heterogeneously distributed across layers. Perturbed cognitive function and abnormal cerebrospinal fluid amyloid-β42 levels correlated positively with the vulnerability of the hub regions in patients with Alzheimer's disease. Our analysis therefore demonstrates that the magnetoencephalography-based multiplex brain networks contain important information that cannot be revealed by frequency-specific brain networks. Furthermore, this indicates that functional networks obtained in different frequency bands do not act as independent entities. Overall, our multiplex network study provides an effective framework to integrate the frequency-specific networks with different frequency patterns and reveal neuropathological mechanism of hub disruption in Alzheimer's disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Visual feature integration with an attention deficit.

PubMed

Arguin, M; Cavanagh, P; Joanette, Y

1994-01-01

Treisman's feature integration theory proposes that the perception of illusory conjunctions of correctly encoded visual features is due to the failure of an attentional process. This hypothesis was examined by studying brain-damaged subjects who had previously been shown to have difficulty in attending to contralesional stimulation. These subjects exhibited a massive feature integration deficit for contralesional stimulation relative to ipsilesional displays. In contrast, both normal age-matched controls and brain-damaged subjects who did not exhibit any evidence of an attention deficit showed comparable feature integration performance with left- and right-hemifield stimulation. These observations indicate the crucial function of attention for visual feature integration in normal perception.

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

PubMed

Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

2017-02-01

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study. © 2016, American College of Rheumatology.

Dynamic reconfiguration of frontal brain networks during executive cognition in humans

PubMed Central

Braun, Urs; Schäfer, Axel; Walter, Henrik; Erk, Susanne; Romanczuk-Seiferth, Nina; Haddad, Leila; Schweiger, Janina I.; Grimm, Oliver; Heinz, Andreas; Tost, Heike; Meyer-Lindenberg, Andreas; Bassett, Danielle S.

2015-01-01

The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of “dynamic network neuroscience” to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the “n-back” task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes “network flexibility,” employs transient and heterogeneous connectivity between frontal systems, which we refer to as “integration.” Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia. PMID:26324898

Age Related Changes in Topological Properties of Brain Functional Network and Structural Connectivity.

PubMed

Shah, Chandan; Liu, Jia; Lv, Peilin; Sun, Huaiqiang; Xiao, Yuan; Liu, Jieke; Zhao, Youjin; Zhang, Wenjing; Yao, Li; Gong, Qiyong; Lui, Su

2018-01-01

Introduction: There are still uncertainties about the true nature of age related changes in topological properties of the brain functional network and its structural connectivity during various developmental stages. In this cross- sectional study, we investigated the effects of age and its relationship with regional nodal properties of the functional brain network and white matter integrity. Method: DTI and fMRI data were acquired from 458 healthy Chinese participants ranging from age 8 to 81 years. Tractography was conducted on the DTI data using FSL. Graph Theory analyses were conducted on the functional data yielding topological properties of the functional network using SPM and GRETNA toolbox. Two multiple regressions were performed to investigate the effects of age on nodal topological properties of the functional brain network and white matter integrity. Result: For the functional studies, we observed that regional nodal characteristics such as node betweenness were decreased while node degree and node efficiency was increased in relation to increasing age. Perversely, we observed that the relationship between nodal topological properties and fasciculus structures were primarily positive for nodal betweenness but negative for nodal degree and nodal efficiency. Decrease in functional nodal betweenness was primarily located in superior frontal lobe, right occipital lobe and the global hubs. These brain regions also had both direct and indirect anatomical relationships with the 14 fiber bundles. A linear age related decreases in the Fractional anisotropy (FA) value was found in the callosum forceps minor. Conclusion: These results suggests that age related differences were more pronounced in the functional than in structural measure indicating these measures do not have direct one-to-one mapping. Our study also indicates that the fiber bundles with longer fibers exhibited a more pronounced effect on the properties of functional network.

Notch3 is necessary for blood vessel integrity in the central nervous system.

PubMed

Henshall, Tanya L; Keller, Annika; He, Liqun; Johansson, Bengt R; Wallgard, Elisabet; Raschperger, Elisabeth; Mäe, Maarja Andaloussi; Jin, Shaobo; Betsholtz, Christer; Lendahl, Urban

2015-02-01

Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution, and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the loss of VSMC in the Notch3(-/-) mouse on blood vessel integrity in the central nervous system. Notch3(-/-) mice showed focal disruptions of the blood-brain barrier demonstrated by extravasation of tracers accompanied by fibrin deposition in the retinal vasculature. This blood-brain barrier leakage was accompanied by a regionalized and patchy loss of VSMC, with VSMC gaps predominantly in arterial resistance vessels of larger caliber. The loss of VSMC appeared to be caused by progressive degeneration of VSMC resulting in a gradual loss of VSMC marker expression and a progressive acquisition of an aberrant VSMC phenotype closer to the gaps, followed by enhanced apoptosis and cellular disintegration in the gaps. Arterial VSMC were the only mural cell type that was morphologically affected, despite Notch3 also being expressed in pericytes. Transcriptome analysis of isolated brain microvessels revealed gene expression changes in Notch3(-/-) mice consistent with loss of arterial VSMC and presumably secondary transcriptional changes were observed in endothelial genes, which may explain the compromised vascular integrity. We demonstrate that Notch3 is important for survival of VSMC, and reveal a critical role for Notch3 and VSMC in blood vessel integrity and blood-brain barrier function in the mammalian vasculature. © 2014 American Heart Association, Inc.

Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

PubMed

Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

2018-06-01

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Planarian shows decision-making behavior in response to multiple stimuli by integrative brain function.

PubMed

Inoue, Takeshi; Hoshino, Hajime; Yamashita, Taiga; Shimoyama, Seira; Agata, Kiyokazu

2015-01-01

Planarians belong to an evolutionarily early group of organisms that possess a central nervous system including a well-organized brain with a simple architecture but many types of neurons. Planarians display a number of behaviors, such as phototaxis and thermotaxis, in response to external stimuli, and it has been shown that various molecules and neural pathways in the brain are involved in controlling these behaviors. However, due to the lack of combinatorial assay methods, it remains obscure whether planarians possess higher brain functions, including integration in the brain, in which multiple signals coming from outside are coordinated and used in determining behavioral strategies. In the present study, we designed chemotaxis and thigmotaxis/kinesis tracking assays to measure several planarian behaviors in addition to those measured by phototaxis and thermotaxis assays previously established by our group, and used these tests to analyze planarian chemotactic and thigmotactic/kinetic behaviors. We found that headless planarian body fragments and planarians that had specifically lost neural activity following regeneration-dependent conditional gene knockdown (Readyknock) of synaptotagmin in the brain lost both chemotactic and thigmotactic behaviors, suggesting that neural activity in the brain is required for the planarian's chemotactic and thigmotactic behaviors. Furthermore, we compared the strength of phototaxis, chemotaxis, thigmotaxis/kinesis, and thermotaxis by presenting simultaneous binary stimuli to planarians. We found that planarians showed a clear order of predominance of these behaviors. For example, when planarians were simultaneously exposed to 400 lux of light and a chemoattractant, they showed chemoattractive behavior irrespective of the direction of the light source, although exposure to light of this intensity alone induces evasive behavior away from the light source. In contrast, when the light intensity was increased to 800 or 1600 lux and the same dose of chemoattractant was presented, planarian behaviors were gradually shifted to negative phototaxis rather than chemoattraction. These results suggest that planarians may be capable of selecting behavioral strategies via the integration of discrete brain functions when exposed to multiple stimuli. The planarian brain processes external signals received through the respective sensory neurons, thereby resulting in the production of appropriate behaviors. In addition, planarians can adjust behavioral features in response to stimulus conditions by integrating multiple external signals in the brain.

Resting state electrical brain activity and connectivity in fibromyalgia

PubMed Central

Vanneste, Sven; Ost, Jan; Van Havenbergh, Tony; De Ridder, Dirk

2017-01-01

The exact mechanism underlying fibromyalgia is unknown, but increased facilitatory modulation and/or dysfunctional descending inhibitory pathway activity are posited as possible mechanisms contributing to sensitization of the central nervous system. The primary goal of this study is to identify a fibromyalgia neural circuit that can account for these abnormalities in central pain. The second goal is to gain a better understanding of the functional connectivity between the default and the executive attention network (salience network plus dorsal lateral prefrontal cortex) in fibromyalgia. We examine neural activity associated with fibromyalgia (N = 44) and compare these with healthy controls (N = 44) using resting state source localized EEG. Our data support an important role of the pregenual anterior cingulate cortex but also suggest that the degree of activation and the degree of integration between different brain areas is important. The inhibition of the connectivity between the dorsal lateral prefrontal cortex and the posterior cingulate cortex on the pain inhibitory pathway seems to be limited by decreased functional connectivity with the pregenual anterior cingulate cortex. Our data highlight the functional dynamics of brain regions integrated in brain networks in fibromyalgia patients. PMID:28650974

Compensatory recruitment of neural resources in chronic alcoholism.

PubMed

Chanraud, Sandra; Sullivan, Edith V

2014-01-01

Functional recovery occurs with sustained sobriety, but the neural mechanisms enabling recovery are only now emerging. Theories about promising mechanisms involve concepts of neuroadaptation, where excessive alcohol consumption results in untoward structural and functional brain changes which are subsequently candidates for reversal with sobriety. Views on functional adaptation in chronic alcoholism have expanded with results from neuroimaging studies. Here, we first describe and define the concept of neuroadaptation according to emerging theories based on the growing literature in aging-related cognitive functioning. Then we describe findings as they apply to chronic alcoholism and factors that could influence compensation, such as functional brain reserve and the integrity of brain structure. Finally, we review brain plasticity based on physiologic mechanisms that could underlie mechanisms of neural compensation. Where possible, we provide operational criteria to define functional and neural compensation. © 2014 Elsevier B.V. All rights reserved.

Complementary aspects of diffusion imaging and fMRI; I: structure and function.

PubMed

Mulkern, Robert V; Davis, Peter E; Haker, Steven J; Estepar, Raul San Jose; Panych, Lawrence P; Maier, Stephan E; Rivkin, Michael J

2006-05-01

Studying the intersection of brain structure and function is an important aspect of modern neuroscience. The development of magnetic resonance imaging (MRI) over the last 25 years has provided new and powerful tools for the study of brain structure and function. Two tools in particular, diffusion imaging and functional MRI (fMRI), are playing increasingly important roles in elucidating the complementary aspects of brain structure and function. In this work, we review basic technical features of diffusion imaging and fMRI for studying the integrity of white matter structural components and for determining the location and extent of cortical activation in gray matter, respectively. We then review a growing body of literature in which the complementary aspects of diffusion imaging and fMRI, applied as separate examinations but analyzed in tandem, have been exploited to enhance our knowledge of brain structure and function.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.

2012-01-01

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

PubMed Central

Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

2016-01-01

Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

Brain mitochondrial bioenergetics change with rapid and prolonged shifts in aggression in the honey bee, Apis mellifera.

PubMed

Rittschof, Clare C; Vekaria, Hemendra J; Palmer, Joseph H; Sullivan, Patrick G

2018-04-25

Neuronal function demands high-level energy production, and as such, a decline in mitochondrial respiration characterizes brain injury and disease. A growing number of studies, however, link brain mitochondrial function to behavioral modulation in non-diseased contexts. In the honey bee, we show for the first time that an acute social interaction, which invokes an aggressive response, may also cause a rapid decline in brain mitochondrial bioenergetics. The degree and speed of this decline has only been previously observed in the context of brain injury. Furthermore, in the honey bee, age-related increases in aggressive tendency are associated with increased baseline brain mitochondrial respiration, as well as increased plasticity in response to metabolic fuel type in vitro Similarly, diet restriction and ketone body feeding, which commonly enhance mammalian brain mitochondrial function in vivo , cause increased aggression. Thus, even in normal behavioral contexts, brain mitochondria show a surprising degree of variation in function over both rapid and prolonged time scales, with age predicting both baseline function and plasticity in function. These results suggest that mitochondrial function is integral to modulating aggression-related neuronal signaling. We hypothesize that variation in function reflects mitochondrial calcium buffering activity, and that shifts in mitochondrial function signal to the neuronal soma to regulate gene expression and neural energetic state. Modulating brain energetic state is emerging as a critical component of the regulation of behavior in non-diseased contexts. © 2018. Published by The Company of Biologists Ltd.

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

PubMed

He, Bin; Sohrabpour, Abbas; Brown, Emery; Liu, Zhongming

2018-06-04

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

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.

A pairwise maximum entropy model accurately describes resting-state human brain networks

PubMed Central

Watanabe, Takamitsu; Hirose, Satoshi; Wada, Hiroyuki; Imai, Yoshio; Machida, Toru; Shirouzu, Ichiro; Konishi, Seiki; Miyashita, Yasushi; Masuda, Naoki

2013-01-01

The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system. Here, we address this issue by demonstrating that a pairwise maximum entropy model, which takes into account region-specific activity rates and pairwise interactions, can be robustly and accurately fitted to resting-state human brain activities obtained by functional magnetic resonance imaging. Furthermore, to validate the approximation of the resting-state networks by the pairwise maximum entropy model, we show that the functional interactions estimated by the pairwise maximum entropy model reflect anatomical connexions more accurately than the conventional functional connectivity method. These findings indicate that a relatively simple statistical model not only captures the structure of the resting-state networks but also provides a possible method to derive physiological information about various large-scale brain networks. PMID:23340410

Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, Barney D; Rao, Stephen M; Li, Shi-Jiang; Hudetz, Anthony G

2012-10-01

Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an functional magnetic resonance imaging-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain. Copyright © 2011 Wiley Periodicals, Inc.

Increased brain connectivity and activation after cognitive rehabilitation in Parkinson's disease: a randomized controlled trial.

PubMed

Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Lucas-Jiménez, Olaia; Gómez-Esteban, Juan Carlos; Gómez-Beldarrain, Maria Ángeles; Ibarretxe-Bilbao, Naroa

2017-12-01

Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson's disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.

Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

PubMed

Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

2018-01-01

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

A programmable laboratory testbed in support of evaluation of functional brain activation and connectivity.

PubMed

Barbour, Randall L; Graber, Harry L; Xu, Yong; Pei, Yaling; Schmitz, Christoph H; Pfeil, Douglas S; Tyagi, Anandita; Andronica, Randy; Lee, Daniel C; Barbour, San-Lian S; Nichols, J David; Pflieger, Mark E

2012-03-01

An important determinant of the value of quantitative neuroimaging studies is the reliability of the derived information, which is a function of the data collection conditions. Near infrared spectroscopy (NIRS) and electroencelphalography are independent sensing domains that are well suited to explore principal elements of the brain's response to neuroactivation, and whose integration supports development of compact, even wearable, systems suitable for use in open environments. In an effort to maximize the translatability and utility of such resources, we have established an experimental laboratory testbed that supports measures and analysis of simulated macroscopic bioelectric and hemodynamic responses of the brain. Principal elements of the testbed include 1) a programmable anthropomorphic head phantom containing a multisignal source array embedded within a matrix that approximates the background optical and bioelectric properties of the brain, 2) integrated translatable headgear that support multimodal studies, and 3) an integrated data analysis environment that supports anatomically based mapping of experiment-derived measures that are directly and not directly observable. Here, we present a description of system components and fabrication, an overview of the analysis environment, and findings from a representative study that document the ability to experimentally validate effective connectivity models based on NIRS tomography.

The behavioral and neural binding phenomena during visuomotor integration of angry facial expressions.

PubMed

Coll, Sélim Yahia; Ceravolo, Leonardo; Frühholz, Sascha; Grandjean, Didier

2018-05-02

Different parts of our brain code the perceptual features and actions related to an object, causing a binding problem, in which the brain has to integrate information related to an event without any interference regarding the features and actions involved in other concurrently processed events. Using a paradigm similar to Hommel, who revealed perception-action bindings, we showed that emotion could bind with motor actions when relevant, and in specific conditions, irrelevant for the task. By adapting our protocol to a functional Magnetic Resonance Imaging paradigm we investigated, in the present study, the neural bases of the emotion-action binding with task-relevant angry faces. Our results showed that emotion bound with motor responses. This integration revealed increased activity in distributed brain areas involved in: (i) memory, including the hippocampi; (ii) motor actions with the precentral gyri; (iii) and emotion processing with the insula. Interestingly, increased activations in the cingulate gyri and putamen, highlighted their potential key role in the emotion-action binding, due to their involvement in emotion processing, motor actions, and memory. The present study confirmed our previous results and point out for the first time the functional brain activity related to the emotion-action association.

Deep Brain Stimulation

PubMed Central

Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

2012-01-01

Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

75 FR 26262 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

...: Learning, Cognition, and Audition. Date: May 27, 2010. Time: 1 p.m. to 3 p.m. Agenda: To review and...: Brain Disorders and Clinical Neuroscience Integrated Review Group; Pathophysiological Basis of [email protected] . Name of Committee: Integrative, Functional and Cognitive Neuroscience Integrated Review...

Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

PubMed

Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

2014-04-01

Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. © 2014 Anatomical Society.

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

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.

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.

Kisspeptin modulates sexual and emotional brain processing in humans.

PubMed

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

2017-02-01

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

Combining Fiber Dissection, Plastination, and Tractography for Neuroanatomical Education: Revealing the Cerebellar Nuclei and Their White Matter Connections

ERIC Educational Resources Information Center

Arnts, Hisse; Kleinnijenhuis, Michiel; Kooloos, Jan G. M.; Schepens-Franke, Annelieke N.; van Cappellen van Walsum, Anne-Marie

2014-01-01

In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white…

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

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia.

PubMed

Mayurasakorn, Korapat; Williams, Jill J; Ten, Vadim S; Deckelbaum, Richard J

2011-03-01

With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between presynaptic and postsynaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing antiapoptotic activities such as decreasing responses to reactive oxygen species, upregulating antiapoptotic protein expression, downregulating apoptotic protein expression, and maintaining mitochondrial integrity and function. DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression.

MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain

PubMed Central

Chanraud, Sandra; Zahr, Natalie; Pfefferbaum, Adolf

2010-01-01

As Norman Geschwind asserted in 1965, syndromes resulting from white matter lesions could produce deficits in higher-order functions and “disconnexion” or the interruption of connection between gray matter regions could be as disruptive as trauma to those regions per se. The advent of in vivo diffusion tensor imaging, which allows quantitative characterization of white matter fiber integrity in health and disease, has served to strengthen Geschwind's proposal. Here we present an overview of the principles of diffusion tensor imaging (DTI) and its contribution to progress in our current understanding of normal and pathological brain function. PMID:20422451

The Topographical Mapping in Drosophila Central Complex Network and Its Signal Routing

PubMed Central

Chang, Po-Yen; Su, Ta-Shun; Shih, Chi-Tin; Lo, Chung-Chuan

2017-01-01

Neural networks regulate brain functions by routing signals. Therefore, investigating the detailed organization of a neural circuit at the cellular levels is a crucial step toward understanding the neural mechanisms of brain functions. To study how a complicated neural circuit is organized, we analyzed recently published data on the neural circuit of the Drosophila central complex, a brain structure associated with a variety of functions including sensory integration and coordination of locomotion. We discovered that, except for a small number of “atypical” neuron types, the network structure formed by the identified 194 neuron types can be described by only a few simple mathematical rules. Specifically, the topological mapping formed by these neurons can be reconstructed by applying a generation matrix on a small set of initial neurons. By analyzing how information flows propagate with or without the atypical neurons, we found that while the general pattern of signal propagation in the central complex follows the simple topological mapping formed by the “typical” neurons, some atypical neurons can substantially re-route the signal pathways, implying specific roles of these neurons in sensory signal integration. The present study provides insights into the organization principle and signal integration in the central complex. PMID:28443014

Altered structure-function relations of semantic processing in youths with high-functioning autism: a combined diffusion and functional MRI study.

PubMed

Lo, Yu-Chun; Chou, Tai-Li; Fan, Li-Ying; Gau, Susan Shur-Fen; Chiu, Yen-Nan; Tseng, Wen-Yih Isaac

2013-12-01

Deficits in language and communication are among the core symptoms of autism, a common neurodevelopmental disorder with long-term impairment. Despite the striking nature of the autistic language impairment, knowledge about its corresponding alterations in the brain is still evolving. We hypothesized that the dual stream language network is altered in autism, and that this alteration could be revealed by changes in the relationships between microstructural integrity and functional activation. The study recruited 20 right-handed male youths with autism and 20 carefully matched individually, typically developing (TD) youths. Microstructural integrity of the left dorsal and left ventral pathways responsible for language processing and the functional activation of the connected brain regions were investigated by using diffusion spectrum imaging and functional magnetic resonance imaging of a semantic task, respectively. Youths with autism had significantly poorer language function, and lower functional activation in left dorsal and left ventral regions of the language network, compared with TD youths. The TD group showed a significant correlation of the functional activation of the left dorsal region with microstructural integrity of the left ventral pathway, whereas the autism group showed a significant correlation of the functional activation of the left ventral region with microstructural integrity of the left dorsal pathway, and moreover verbal comprehension index was correlated with microstructural integrity of the left ventral pathway. These altered structure-function relationships in autism suggest possible involvement of the dual pathways in supporting deficient semantic processing. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

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

PubMed

De Witte, Nele A J; Mueller, Sven C

2017-12-01

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

Recruiting specialized macrophages across the borders to restore brain functions.

PubMed

Corraliza, Inés

2014-01-01

Although is well accepted that the central nervous system has an immune privilege protected by the blood-brain barrier (BBB) and maintained by the glia, it is also known that in homeostatic conditions, peripheral immune cells are able to penetrate to the deepest regions of brain without altering the structural integrity of the BBB. Nearly all neurological diseases, including degenerative, autoimmune or infectious ones, compromising brain functions, develop with a common pattern of inflammation in which macrophages and microglia activation have been regarded often as the "bad guys." However, recognizing the huge heterogeneity of macrophage populations and also the different expression properties of microglia, there is increasing evidence of alternative conditions in which these cells, if primed and addressed in the correct direction, could be essential for reparative and regenerative functions. The main proposal of this review is to integrate studies about macrophage's biology at the brain borders where the ultimate challenge is to penetrate through the BBB and contribute to change or even stop the course of disease. Thanks to the efforts made in the last century, this special wall is currently recognized as a highly regulated cooperative structure, in which their components form neurovascular units. This new scenario prompted us to review the precise cross-talk between the mind and body modes of immune response.

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

The impact of microglial activation on blood-brain barrier in brain diseases

PubMed Central

da Fonseca, Anna Carolina Carvalho; Matias, Diana; Garcia, Celina; Amaral, Rackele; Geraldo, Luiz Henrique; Freitas, Catarina; Lima, Flavia Regina Souza

2014-01-01

The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. PMID:25404894

Inferring multi-scale neural mechanisms with brain network modelling

PubMed Central

Schirner, Michael; McIntosh, Anthony Randal; Jirsa, Viktor; Deco, Gustavo

2018-01-01

The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies. PMID:29308767

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

The Neural Mechanisms of Meditative Practices: Novel Approaches for Healthy Aging.

PubMed

Acevedo, Bianca P; Pospos, Sarah; Lavretsky, Helen

2016-01-01

Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e.g., yoga) that combine movement, including chanting, with breath practices and meditation. Recent meta-analyses and individual studies demonstrated common brain effects for attention-based meditative practices and active-based meditations in areas involved in reward processing and learning, attention and memory, awareness and sensory integration, and self-referential processing and emotional control, while deactivation was seen in the amygdala, an area implicated in emotion processing. Unique effects for mindfulness practices were found in brain regions involved in body awareness, attention, and the integration of emotion and sensory processing. Effects specific to active-based meditations appeared in brain areas involved in self-control, social cognition, language, speech, tactile stimulation, sensorimotor integration, and motor function. This review suggests that mind-body practices can target different brain systems that are involved in the regulation of attention, emotional control, mood, and executive cognition that can be used to treat or prevent mood and cognitive disorders of aging, such as depression and caregiver stress, or serve as "brain fitness" exercise. Benefits may include improving brain functional connectivity in brain systems that generally degenerate with Alzheimer's disease, Parkinson's disease, and other aging-related diseases.

Simultaneous EEG and MEG source reconstruction in sparse electromagnetic source imaging.

PubMed

Ding, Lei; Yuan, Han

2013-04-01

Electroencephalography (EEG) and magnetoencephalography (MEG) have different sensitivities to differently configured brain activations, making them complimentary in providing independent information for better detection and inverse reconstruction of brain sources. In the present study, we developed an integrative approach, which integrates a novel sparse electromagnetic source imaging method, i.e., variation-based cortical current density (VB-SCCD), together with the combined use of EEG and MEG data in reconstructing complex brain activity. To perform simultaneous analysis of multimodal data, we proposed to normalize EEG and MEG signals according to their individual noise levels to create unit-free measures. Our Monte Carlo simulations demonstrated that this integrative approach is capable of reconstructing complex cortical brain activations (up to 10 simultaneously activated and randomly located sources). Results from experimental data showed that complex brain activations evoked in a face recognition task were successfully reconstructed using the integrative approach, which were consistent with other research findings and validated by independent data from functional magnetic resonance imaging using the same stimulus protocol. Reconstructed cortical brain activations from both simulations and experimental data provided precise source localizations as well as accurate spatial extents of localized sources. In comparison with studies using EEG or MEG alone, the performance of cortical source reconstructions using combined EEG and MEG was significantly improved. We demonstrated that this new sparse ESI methodology with integrated analysis of EEG and MEG data could accurately probe spatiotemporal processes of complex human brain activations. This is promising for noninvasively studying large-scale brain networks of high clinical and scientific significance. Copyright © 2011 Wiley Periodicals, Inc.

Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

PubMed Central

Natarajan, Reka; Northrop, Nicole

2017-01-01

The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

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

PubMed

Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz

2015-01-01

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

How is the brain working?: Research on brain oscillations and connectivities in a new "Take-Off" state.

PubMed

Başar, Erol; Düzgün, Aysel

2016-05-01

The present report is a trial to survey analysis and applications of brain oscillations in cognitive impairment for opening the way to a new take off in research on brain oscillation. Although the number of papers related to brain oscillations rapidly increases, it is important to indicate the common principles governing the functioning of brain oscillations in the brain and body. Research scientists need a global view on the types of analysis, applications and existing oscillations. Further, scientists dealing with brain oscillations must have some knowledge from theoretical physics, system theory, and also general philosophy. The neuroscientists working on brain oscillations can mentally integrate several papers in the present report, and try to discover new avenues to augment knowledge on brain functions. A new take off in the search of brain oscillations indicates the strong need to survey this brunch of neuroscience in a broad panoply of science. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Experiences of giving and receiving care in traumatic brain injury: An integrative review.

PubMed

Kivunja, Stephen; River, Jo; Gullick, Janice

2018-04-01

To synthesise the literature on the experiences of giving or receiving care for traumatic brain injury for people with traumatic brain injury, their family members and nurses in hospital and rehabilitation settings. Traumatic brain injury represents a major source of physical, social and economic burden. In the hospital setting, people with traumatic brain injury feel excluded from decision-making processes and perceive impatient care. Families describe inadequate information and support for psychological distress. Nurses find the care of people with traumatic brain injury challenging particularly when experiencing heavy workloads. To date, a contemporary synthesis of the literature on people with traumatic brain injury, family and nurse experiences of traumatic brain injury care has not been conducted. Integrative literature review. A systematic search strategy guided by the PRISMA statement was conducted in CINAHL, PubMed, Proquest, EMBASE and Google Scholar. Whittemore and Knafl's (Journal of Advanced Nursing, 52, 2005, 546) integrative review framework guided data reduction, data display, data comparison and conclusion verification. Across the three participant categories (people with traumatic brain injury/family members/nurses) and sixteen subcategories, six cross-cutting themes emerged: seeking personhood, navigating challenging behaviour, valuing skills and competence, struggling with changed family responsibilities, maintaining productive partnerships and reflecting on workplace culture. Traumatic brain injury creates changes in physical, cognitive and emotional function that challenge known ways of being in the world for people. This alters relationship dynamics within families and requires a specific skill set among nurses. Recommendations include the following: (i) formal inclusion of people with traumatic brain injury and families in care planning, (ii) routine risk screening for falls and challenging behaviour to ensure that controls are based on accurate assessment, (iii) formal orientation and training for novice nurses in the management of challenging behaviour, (iv) professional case management to guide access to services and funding and (v) personal skill development to optimise family functioning. © 2018 John Wiley & Sons Ltd.

The Effects of Spaceflight and Head Down Tilt Bed Rest on Neurocognitive Performance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, Rachael D.; Bloomberg, Jacob; Wood, Scott; Mulavara, Ajit; Kofman, Igor; De Dios, Yiri; Gadd, Nicole; Stepanyan, Vahagn

2017-01-01

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. specific Aims: Aim 1-Identify changes in brain structure, function, and network integrity as a function of head down tilt bed rest and spaceflight, and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

An integrative architecture for general intelligence and executive function revealed by lesion mapping

PubMed Central

Colom, Roberto; Solomon, Jeffrey; Krueger, Frank; Forbes, Chad; Grafman, Jordan

2012-01-01

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control, the broader functional networks that support high-level cognition and give rise to general intelligence remain to be well characterized. Here, we investigated the neural substrates of the general factor of intelligence (g) and executive function in 182 patients with focal brain damage using voxel-based lesion–symptom mapping. The Wechsler Adult Intelligence Scale and Delis–Kaplan Executive Function System were used to derive measures of g and executive function, respectively. Impaired performance on these measures was associated with damage to a distributed network of left lateralized brain areas, including regions of frontal and parietal cortex and white matter association tracts, which bind these areas into a coordinated system. The observed findings support an integrative framework for understanding the architecture of general intelligence and executive function, supporting their reliance upon a shared fronto-parietal network for the integration and control of cognitive representations and making specific recommendations for the application of the Wechsler Adult Intelligence Scale and Delis–Kaplan Executive Function System to the study of high-level cognition in health and disease. PMID:22396393

Multisensory integration processing during olfactory-visual stimulation-An fMRI graph theoretical network analysis.

PubMed

Ripp, Isabelle; Zur Nieden, Anna-Nora; Blankenagel, Sonja; Franzmeier, Nicolai; Lundström, Johan N; Freiherr, Jessica

2018-05-07

In this study, we aimed to understand how whole-brain neural networks compute sensory information integration based on the olfactory and visual system. Task-related functional magnetic resonance imaging (fMRI) data was obtained during unimodal and bimodal sensory stimulation. Based on the identification of multisensory integration processing (MIP) specific hub-like network nodes analyzed with network-based statistics using region-of-interest based connectivity matrices, we conclude the following brain areas to be important for processing the presented bimodal sensory information: right precuneus connected contralaterally to the supramarginal gyrus for memory-related imagery and phonology retrieval, and the left middle occipital gyrus connected ipsilaterally to the inferior frontal gyrus via the inferior fronto-occipital fasciculus including functional aspects of working memory. Applied graph theory for quantification of the resulting complex network topologies indicates a significantly increased global efficiency and clustering coefficient in networks including aspects of MIP reflecting a simultaneous better integration and segregation. Graph theoretical analysis of positive and negative network correlations allowing for inferences about excitatory and inhibitory network architectures revealed-not significant, but very consistent-that MIP-specific neural networks are dominated by inhibitory relationships between brain regions involved in stimulus processing. © 2018 Wiley Periodicals, Inc.

[Impact of acquired brain injury towards the community integration: employment outcome, disability and dependence two years after injury].

PubMed

Luna-Lario, P; Ojeda, N; Tirapu-Ustarroz, J; Pena, J

2016-06-16

To analyze the impact of acquired brain injury towards the community integration (professional career, disability, and dependence) in a sample of people affected by vascular, traumatic and tumor etiology acquired brain damage, over a two year time period after the original injury, and also to examine what sociodemographic variables, premorbid and injury related clinical data can predict the level of the person's integration into the community. 106 adults sample suffering from acquired brain injury who were attended by the Neuropsychology and Neuropsychiatry Department at Hospital of Navarra (Spain) affected by memory deficit as their main sequel. Differences among groups have been analyzed by using t by Student, chi squared and U by Mann-Whitney tests. 19% and 29% of the participants who were actively working before the injury got back their previous status within one and two years time respectively. 45% of the total sample were recognized disabled and 17% dependant. No relationship between sociodemographic and clinical variables and functional parameters observed were found. Acquired brain damage presents a high intensity impact on affected person's life trajectory. Nevertheless, in Spain, its consequences at sociolaboral adjustment over the the two years following the damage through functional parameters analyzed with official governmental means over a vascular, traumatic and tumor etiology sample had never been studied before.

A prospective study to evaluate a new residential community reintegration programme for severe chronic brain injury: the Brain Integration Programme.

PubMed

Geurtsen, G J; Martina, J D; Van Heugten, C M; Geurts, A C H

2008-07-01

To assess the effectiveness of a residential community reintegration programme for participants with chronic sequelae of severe acquired brain injury that hamper community functioning. Prospective cohort study. Twenty-four participants with acquired brain injury (traumatic n = 18; stroke n = 3, tumour n = 2, encephalitis n = 1). Participants had impaired illness awareness, alcohol and drug problems and/or behavioural problems. A skills-oriented programme with modules related to independent living, work, social and emotional well-being. The Community Integration Questionnaire, CES-Depression, EuroQOL, Employability Rating Scale, living situation and work status were scored at the start (T0), end of treatment (T1) and 1-year follow-up (T2). Significant effects on the majority of outcome measures were present at T1. Employability significantly improved at T2 and living independently rose from 42% to over 70%. Participants working increased from 38% to 58% and the hours of work per week increased from 8 to 15. The Brain Integration Programme led to a sustained reduction in experienced problems and improved community integration. It is concluded that even participants with complex problems due to severe brain injury who got stuck in life could improve their social participation and emotional well-being through a residential community reintegration programme.

Integrative biological analysis for neuropsychopharmacology.

PubMed

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

2014-01-01

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

Features of spatial and functional segregation and integration of the primate connectome revealed by trade-off between wiring cost and efficiency

PubMed Central

Chen, Yuhan; Wang, Shengjun

2017-01-01

The primate connectome, possessing a characteristic global topology and specific regional connectivity profiles, is well organized to support both segregated and integrated brain function. However, the organization mechanisms shaping the characteristic connectivity and its relationship to functional requirements remain unclear. The primate brain connectome is shaped by metabolic economy as well as functional values. Here, we explored the influence of two competing factors and additional advanced functional requirements on the primate connectome employing an optimal trade-off model between neural wiring cost and the representative functional requirement of processing efficiency. Moreover, we compared this model with a generative model combining spatial distance and topological similarity, with the objective of statistically reproducing multiple topological features of the network. The primate connectome indeed displays a cost-efficiency trade-off and that up to 67% of the connections were recovered by optimal combination of the two basic factors of wiring economy and processing efficiency, clearly higher than the proportion of connections (56%) explained by the generative model. While not explicitly aimed for, the trade-off model captured several key topological features of the real connectome as the generative model, yet better explained the connectivity of most regions. The majority of the remaining 33% of connections unexplained by the best trade-off model were long-distance links, which are concentrated on few cortical areas, termed long-distance connectors (LDCs). The LDCs are mainly non-hubs, but form a densely connected group overlapping on spatially segregated functional modalities. LDCs are crucial for both functional segregation and integration across different scales. These organization features revealed by the optimization analysis provide evidence that the demands of advanced functional segregation and integration among spatially distributed regions may play a significant role in shaping the cortical connectome, in addition to the basic cost-efficiency trade-off. These findings also shed light on inherent vulnerabilities of brain networks in diseases. PMID:28961235

Features of spatial and functional segregation and integration of the primate connectome revealed by trade-off between wiring cost and efficiency.

PubMed

Chen, Yuhan; Wang, Shengjun; Hilgetag, Claus C; Zhou, Changsong

2017-09-01

The primate connectome, possessing a characteristic global topology and specific regional connectivity profiles, is well organized to support both segregated and integrated brain function. However, the organization mechanisms shaping the characteristic connectivity and its relationship to functional requirements remain unclear. The primate brain connectome is shaped by metabolic economy as well as functional values. Here, we explored the influence of two competing factors and additional advanced functional requirements on the primate connectome employing an optimal trade-off model between neural wiring cost and the representative functional requirement of processing efficiency. Moreover, we compared this model with a generative model combining spatial distance and topological similarity, with the objective of statistically reproducing multiple topological features of the network. The primate connectome indeed displays a cost-efficiency trade-off and that up to 67% of the connections were recovered by optimal combination of the two basic factors of wiring economy and processing efficiency, clearly higher than the proportion of connections (56%) explained by the generative model. While not explicitly aimed for, the trade-off model captured several key topological features of the real connectome as the generative model, yet better explained the connectivity of most regions. The majority of the remaining 33% of connections unexplained by the best trade-off model were long-distance links, which are concentrated on few cortical areas, termed long-distance connectors (LDCs). The LDCs are mainly non-hubs, but form a densely connected group overlapping on spatially segregated functional modalities. LDCs are crucial for both functional segregation and integration across different scales. These organization features revealed by the optimization analysis provide evidence that the demands of advanced functional segregation and integration among spatially distributed regions may play a significant role in shaping the cortical connectome, in addition to the basic cost-efficiency trade-off. These findings also shed light on inherent vulnerabilities of brain networks in diseases.

Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders.

PubMed

Kana, Rajesh K; Libero, Lauren E; Moore, Marie S

2011-12-01

Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to 'disrupted cortical connectivity' to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD. Published by Elsevier B.V.

Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kana, Rajesh K.; Libero, Lauren E.; Moore, Marie S.

2011-12-01

Recent findings of neurological functioning in autism spectrum disorder (ASD) point to altered brain connectivity as a key feature of its pathophysiology. The cortical underconnectivity theory of ASD (Just et al., 2004) provides an integrated framework for addressing these new findings. This theory suggests that weaker functional connections among brain areas in those with ASD hamper their ability to accomplish complex cognitive and social tasks successfully. We will discuss this theory, but will modify the term underconnectivity to ‘disrupted cortical connectivity’ to capture patterns of both under- and over-connectivity in the brain. In this paper, we will review the existing literature on ASD to marshal supporting evidence for hypotheses formulated on the disrupted cortical connectivity theory. These hypotheses are: 1) underconnectivity in ASD is manifested mainly in long-distance cortical as well as subcortical connections rather than in short-distance cortical connections; 2) underconnectivity in ASD is manifested only in complex cognitive and social functions and not in low-level sensory and perceptual tasks; 3) functional underconnectivity in ASD may be the result of underlying anatomical abnormalities, such as problems in the integrity of white matter; 4) the ASD brain adapts to underconnectivity through compensatory strategies such as overconnectivity mainly in frontal and in posterior brain areas. This may be manifested as deficits in tasks that require frontal-parietal integration. While overconnectivity can be tested by examining the cortical minicolumn organization, long-distance underconnectivity can be tested by cognitively demanding tasks; and 5) functional underconnectivity in brain areas in ASD will be seen not only during complex tasks but also during task-free resting states. We will also discuss some empirical predictions that can be tested in future studies, such as: 1) how disrupted connectivity relates to cognitive impairments in skills such as Theory-of-Mind, cognitive flexibility, and information processing; and 2) how connection abnormalities relate to, and may determine, behavioral symptoms hallmarked by the triad of Impairments in ASD. Furthermore, we will relate the disrupted cortical connectivity model to existing cognitive and neural models of ASD.

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

PubMed Central

Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2013-01-01

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli. PMID:24253232

Sigmund Freud-early network theories of the brain.

PubMed

Surbeck, Werner; Killeen, Tim; Vetter, Johannes; Hildebrandt, Gerhard

2018-06-01

Since the early days of modern neuroscience, psychological models of brain function have been a key component in the development of new knowledge. These models aim to provide a framework that allows the integration of discoveries derived from the fundamental disciplines of neuroscience, including anatomy and physiology, as well as clinical neurology and psychiatry. During the initial stages of his career, Sigmund Freud (1856-1939), became actively involved in these nascent fields with a burgeoning interest in functional neuroanatomy. In contrast to his contemporaries, Freud was convinced that cognition could not be localised to separate modules and that the brain processes cognition not in a merely serial manner but in a parallel and dynamic fashion-anticipating fundamental aspects of current network theories of brain function. This article aims to shed light on Freud's seminal, yet oft-overlooked, early work on functional neuroanatomy and his reasons for finally abandoning the conventional neuroscientific "brain-based" reference frame in order to conceptualise the mind from a purely psychological perspective.

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

NASA Astrophysics Data System (ADS)

Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2013-11-01

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli.

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

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.

Iconic memory and parietofrontal network: fMRI study using temporal integration.

PubMed

Saneyoshi, Ayako; Niimi, Ryosuke; Suetsugu, Tomoko; Kaminaga, Tatsuro; Yokosawa, Kazuhiko

2011-08-03

We investigated the neural basis of iconic memory using functional magnetic resonance imaging. The parietofrontal network of selective attention is reportedly relevant to readout from iconic memory. We adopted a temporal integration task that requires iconic memory but not selective attention. The results showed that the task activated the parietofrontal network, confirming that the network is involved in readout from iconic memory. We further tested a condition in which temporal integration was performed by visual short-term memory but not by iconic memory. However, no brain region revealed higher activation for temporal integration by iconic memory than for temporal integration by visual short-term memory. This result suggested that there is no localized brain region specialized for iconic memory per se.

The Characterization of Brain Behavior Relationships via Cognitive Neuroinformatic Approaches

ERIC Educational Resources Information Center

Kalar, Donald James, II

2009-01-01

The scope, breadth, and volume of data characterizing our current understanding of how the brain functions is growing at an increasingly rapid pace. What is more, theories are becoming increasing complex and nuanced, integrating knowledge from multiple previously independent sources of scientific inquiry. The research described within this…

Relationship of caregiver and family functioning to participation outcomes after postacute rehabilitation for traumatic brain injury: a multicenter investigation.

PubMed

Sander, Angelle M; Maestas, Kacey Little; Sherer, Mark; Malec, James F; Nakase-Richardson, Risa

2012-05-01

To investigate the contribution of caregiver emotional functioning and family functioning to participation outcomes after postacute rehabilitation for traumatic brain injury (TBI). Prospective cohort study. Three postacute comprehensive-integrated postacute rehabilitation programs associated with National Institute on Disability and Rehabilitation Research-funded TBI Model Systems Centers. Persons with medically documented TBI (N=136; 57% with severe TBI, 12% moderate, 31% mild), primarily men and 69% white. Not applicable. Community Integration Questionnaire and Craig Handicap Assessment and Reporting Technique (CHART). After accounting for age, education, sex, and race/ethnicity, there was a significant interaction between caregiver emotional functioning and time since injury for CHART Occupation and Social Integration Scale scores. Better emotional functioning in caregivers was associated with greater occupation and social integration outcomes for persons who entered the postacute rehabilitation program within 6 months of injury, but not for those >6 months postinjury. There was no relationship of family functioning to participation outcomes, and no interaction between family functioning and time since injury. Caregiver distress should be accounted for in studies investigating the effectiveness of postacute rehabilitation after TBI. Screening of caregivers early during postacute rehabilitation can target those who need assistance to improve their support of the person with TBI. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S

2012-12-13

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Patient navigation for traumatic brain injury promotes community re-integration and reduces re-hospitalizations.

PubMed

Rosario, Emily R; Espinoza, Laura; Kaplan, Stephanie; Khonsari, Sepehr; Thurndyke, Earl; Bustos, Melissa; Vickers, Kayla; Navarro, Brittney; Scudder, Bonnie

2017-01-01

To determine the effectiveness of a Navigation programme for patients with traumatic brain injury. Prospective programme evaluation. Inpatient rehabilitation facility and community settings. Eighteen individuals who suffered a traumatic brain injury (TBI), were between the ages of 16-70 years, and had a Rancho Score greater than IV. Patient navigation programme focused on identifying and addressing barriers to positive outcomes, including coordination of care and facilitating communication among the family and healthcare providers, psychosocial support, caregiver support, adherence to treatment, education, community resources and financial issues. Functional status, re-hospitalizations, falls, neurobehavioral symptom inventory, neuroendocrine status, activities of daily living, community integration and caregiver burden. There was a significant reduction in re-hospitalization and fall rate when comparing individuals who received navigation services and those who did not. We also observed improved adherence treatment plans and a significant increase in community integration, independence level and functional abilities. This study begins to highlight the effectiveness of a patient navigation programme for individuals with TBI. Future research with a larger sample will continue to help us refine patient navigation for chronic disabling conditions and determine its sustainability.

Neural Integration in Body Perception.

PubMed

Ramsey, Richard

2018-06-19

The perception of other people is instrumental in guiding social interactions. For example, the appearance of the human body cues a wide range of inferences regarding sex, age, health, and personality, as well as emotional state and intentions, which influence social behavior. To date, most neuroscience research on body perception has aimed to characterize the functional contribution of segregated patches of cortex in the ventral visual stream. In light of the growing prominence of network architectures in neuroscience, the current article reviews neuroimaging studies that measure functional integration between different brain regions during body perception. The review demonstrates that body perception is not restricted to processing in the ventral visual stream but instead reflects a functional alliance between the ventral visual stream and extended neural systems associated with action perception, executive functions, and theory of mind. Overall, these findings demonstrate how body percepts are constructed through interactions in distributed brain networks and underscore that functional segregation and integration should be considered together when formulating neurocognitive theories of body perception. Insight from such an updated model of body perception generalizes to inform the organizational structure of social perception and cognition more generally and also informs disorders of body image, such as anorexia nervosa, which may rely on atypical integration of body-related information.

The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder.

PubMed

Doucet, Gaelle E; Bassett, Danielle S; Yao, Nailin; Glahn, David C; Frangou, Sophia

2017-12-01

Bipolar disorder is a heritable disorder characterized by mood dysregulation associated with brain functional dysconnectivity. Previous research has focused on the detection of risk- and disease-associated dysconnectivity in individuals with bipolar disorder and their first-degree relatives. The present study seeks to identify adaptive brain connectivity features associated with resilience, defined here as avoidance of illness or delayed illness onset in unaffected siblings of patients with bipolar disorder. Graph theoretical methods were used to examine global and regional brain network topology in head-motion-corrected resting-state functional MRI data acquired from 78 patients with bipolar disorder, 64 unaffected siblings, and 41 healthy volunteers. Global network properties were preserved in patients and their siblings while both groups showed reductions in the cohesiveness of the sensorimotor network. In the patient group, these sensorimotor network abnormalities were coupled with reduced integration of core default mode network regions in the ventromedial cortex and hippocampus. Conversely, integration of the default mode network was increased in the sibling group compared with both the patient group and the healthy volunteer group. The authors found that trait-related vulnerability to bipolar disorder was associated with reduced resting-state cohesiveness of the sensorimotor network in patients with bipolar disorder. However, integration of the default mode network emerged as a key feature differentiating disease expression and resilience between the patients and their siblings. This is indicative of the presence of neural mechanisms that may promote resilience, or at least delay illness onset.

Real-Time fMRI Pattern Decoding and Neurofeedback Using FRIEND: An FSL-Integrated BCI Toolbox

PubMed Central

Sato, João R.; Basilio, Rodrigo; Paiva, Fernando F.; Garrido, Griselda J.; Bramati, Ivanei E.; Bado, Patricia; Tovar-Moll, Fernanda; Zahn, Roland; Moll, Jorge

2013-01-01

The demonstration that humans can learn to modulate their own brain activity based on feedback of neurophysiological signals opened up exciting opportunities for fundamental and applied neuroscience. Although EEG-based neurofeedback has been long employed both in experimental and clinical investigation, functional MRI (fMRI)-based neurofeedback emerged as a promising method, given its superior spatial resolution and ability to gauge deep cortical and subcortical brain regions. In combination with improved computational approaches, such as pattern recognition analysis (e.g., Support Vector Machines, SVM), fMRI neurofeedback and brain decoding represent key innovations in the field of neuromodulation and functional plasticity. Expansion in this field and its applications critically depend on the existence of freely available, integrated and user-friendly tools for the neuroimaging research community. Here, we introduce FRIEND, a graphic-oriented user-friendly interface package for fMRI neurofeedback and real-time multivoxel pattern decoding. The package integrates routines for image preprocessing in real-time, ROI-based feedback (single-ROI BOLD level and functional connectivity) and brain decoding-based feedback using SVM. FRIEND delivers an intuitive graphic interface with flexible processing pipelines involving optimized procedures embedding widely validated packages, such as FSL and libSVM. In addition, a user-defined visual neurofeedback module allows users to easily design and run fMRI neurofeedback experiments using ROI-based or multivariate classification approaches. FRIEND is open-source and free for non-commercial use. Processing tutorials and extensive documentation are available. PMID:24312569

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.

TVB-EduPack—An Interactive Learning and Scripting Platform for The Virtual Brain

PubMed Central

Matzke, Henrik; Schirner, Michael; Vollbrecht, Daniel; Rothmeier, Simon; Llarena, Adalberto; Rojas, Raúl; Triebkorn, Paul; Domide, Lia; Mersmann, Jochen; Solodkin, Ana; Jirsa, Viktor K.; McIntosh, Anthony Randal; Ritter, Petra

2015-01-01

The Virtual Brain (TVB; thevirtualbrain.org) is a neuroinformatics platform for full brain network simulation based on individual anatomical connectivity data. The framework addresses clinical and neuroscientific questions by simulating multi-scale neural dynamics that range from local population activity to large-scale brain function and related macroscopic signals like electroencephalography and functional magnetic resonance imaging. TVB is equipped with a graphical and a command-line interface to create models that capture the characteristic biological variability to predict the brain activity of individual subjects. To enable researchers from various backgrounds a quick start into TVB and brain network modeling in general, we developed an educational module: TVB-EduPack. EduPack offers two educational functionalities that seamlessly integrate into TVB's graphical user interface (GUI): (i) interactive tutorials introduce GUI elements, guide through the basic mechanics of software usage and develop complex use-case scenarios; animations, videos and textual descriptions transport essential principles of computational neuroscience and brain modeling; (ii) an automatic script generator records model parameters and produces input files for TVB's Python programming interface; thereby, simulation configurations can be exported as scripts that allow flexible customization of the modeling process and self-defined batch- and post-processing applications while benefitting from the full power of the Python language and its toolboxes. This article covers the implementation of TVB-EduPack and its integration into TVB architecture. Like TVB, EduPack is an open source community project that lives from the participation and contribution of its users. TVB-EduPack can be obtained as part of TVB from thevirtualbrain.org. PMID:26635597

Kisspeptin modulates sexual and emotional brain processing in humans

PubMed Central

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

2017-01-01

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

The Hierarchy of Brain Networks Is Related to Insulin Growth Factor-1 in a Large, Middle-Aged, Healthy Cohort: An Exploratory Magnetoencephalography Study.

PubMed

Sorrentino, Pierpaolo; Nieboer, Dagmar; Twisk, Jos W R; Stam, Cornelis J; Douw, Linda; Hillebrand, Arjan

2017-06-01

Recently, a large study demonstrated that lower serum levels of insulin growth factor-1 (IGF-1) relate to brain atrophy and to a greater risk for developing Alzheimer's disease in a healthy elderly population. We set out to test if functional brain networks relate to IGF-1 levels in the middle aged. Hence, we studied the association between IGF-1 and magnetoencephalography-based functional network characteristics in a middle-aged population. The functional connections between brain areas were estimated for six frequency bands (delta, theta, alpha1, alpha2, beta, gamma) using the phase lag index. Subsequently, the topology of the frequency-specific functional networks was characterized using the minimum spanning tree. Our results showed that lower levels of serum IGF-1 relate to a globally less integrated functional network in the beta and theta band. The associations remained significant when correcting for gender and systemic effects of IGF-1 that might indirectly affect the brain. The value of this exploratory study is the demonstration that lower levels of IGF-1 are associated with brain network topology in the middle aged.

Brain evolution and development: adaptation, allometry and constraint

PubMed Central

Barton, Robert A.

2016-01-01

Phenotypic traits are products of two processes: evolution and development. But how do these processes combine to produce integrated phenotypes? Comparative studies identify consistent patterns of covariation, or allometries, between brain and body size, and between brain components, indicating the presence of significant constraints limiting independent evolution of separate parts. These constraints are poorly understood, but in principle could be either developmental or functional. The developmental constraints hypothesis suggests that individual components (brain and body size, or individual brain components) tend to evolve together because natural selection operates on relatively simple developmental mechanisms that affect the growth of all parts in a concerted manner. The functional constraints hypothesis suggests that correlated change reflects the action of selection on distributed functional systems connecting the different sub-components, predicting more complex patterns of mosaic change at the level of the functional systems and more complex genetic and developmental mechanisms. These hypotheses are not mutually exclusive but make different predictions. We review recent genetic and neurodevelopmental evidence, concluding that functional rather than developmental constraints are the main cause of the observed patterns. PMID:27629025

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

PubMed

Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan

2017-09-01

Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691. © 2017 American Heart Association, Inc.

Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study

PubMed Central

Samson, Andrea C.; Kirsch, Valerie; Blautzik, Janusch; Grothe, Michel; Erat, Okan; Hegenloh, Michael; Coates, Ute; Reiser, Maximilian F.; Hennig-Fast, Kristina; Meindl, Thomas

2013-01-01

Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration. PMID:23825652

SOCIAL: an integrative framework for the development of social skills.

PubMed

Beauchamp, Miriam H; Anderson, Vicki

2010-01-01

Despite significant advances in the field of social neuroscience, much remains to be understood regarding the development and maintenance of social skills across the life span. Few comprehensive models exist that integrate multidisciplinary perspectives and explain the multitude of factors that influence the emergence and expression of social skills. Here, a developmental biopsychosocial model (SOCIAL) is offered that incorporates the biological underpinnings and socio-cognitive skills that underlie social function (attention/executive function, communication, socio-emotional skills), as well as the internal and external (environmental) factors that mediate these skills. The components of the model are discussed in the context of the social brain network and are supported by evidence from 3 conditions known to affect social functioning (autism spectrum disorders, schizophrenia, and traumatic brain injury). This integrative model is intended to provide a theoretical structure for understanding the origins of social dysfunction and the factors that influence the emergence of social skills through childhood and adolescence in both healthy and clinical populations.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Connectivity patterns during music listening: Evidence for action-based processing in musicians.

PubMed

Alluri, Vinoo; Toiviainen, Petri; Burunat, Iballa; Kliuchko, Marina; Vuust, Peter; Brattico, Elvira

2017-06-01

Musical expertise is visible both in the morphology and functionality of the brain. Recent research indicates that functional integration between multi-sensory, somato-motor, default-mode (DMN), and salience (SN) networks of the brain differentiates musicians from non-musicians during resting state. Here, we aimed at determining whether brain networks differentially exchange information in musicians as opposed to non-musicians during naturalistic music listening. Whole-brain graph-theory analyses were performed on participants' fMRI responses. Group-level differences revealed that musicians' primary hubs comprised cerebral and cerebellar sensorimotor regions whereas non-musicians' dominant hubs encompassed DMN-related regions. Community structure analyses of the key hubs revealed greater integration of motor and somatosensory homunculi representing the upper limbs and torso in musicians. Furthermore, musicians who started training at an earlier age exhibited greater centrality in the auditory cortex, and areas related to top-down processes, attention, emotion, somatosensory processing, and non-verbal processing of speech. We here reveal how brain networks organize themselves in a naturalistic music listening situation wherein musicians automatically engage neural networks that are action-based while non-musicians use those that are perception-based to process an incoming auditory stream. Hum Brain Mapp 38:2955-2970, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia

PubMed Central

Mayurasakorn, Korapat; Williams, Jill J.; Ten, Vadim S.; Deckelbaum, Richard J.

2014-01-01

Purpose of review With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. Recent findings DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between pre-and post-synaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing anti-apoptotic activities such as decreasing responses to reactive oxygen species, up-regulating anti-apoptotic protein expression, down-regulating apoptotic protein expression, and maintaining mitochondrial integrity and function. Summary DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression. PMID:21178607

Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A

2017-09-01

In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

Integrating Neuroscience Knowledge and Neuropsychiatric Skills Into Psychiatry: The Way Forward.

PubMed

Schildkrout, Barbara; Benjamin, Sheldon; Lauterbach, Margo D

2016-05-01

Increasing the integration of neuroscience knowledge and neuropsychiatric skills into general psychiatric practice would facilitate expanded approaches to diagnosis, formulation, and treatment while positioning practitioners to utilize findings from emerging brain research. There is growing consensus that the field of psychiatry would benefit from more familiarity with neuroscience and neuropsychiatry. Yet there remain numerous factors impeding the integration of these domains of knowledge into general psychiatry.The authors make recommendations to move the field forward, focusing on the need for advocacy by psychiatry and medical organizations and changes in psychiatry education at all levels. For individual psychiatrists, the recommendations target obstacles to attaining expanded neuroscience and neuropsychiatry education and barriers stemming from widely held, often unspoken beliefs. For the system of psychiatric care, recommendations address the conceptual and physical separation of psychiatry from medicine, overemphasis on the Diagnostic and Statistical Manual of Mental Disorders and on psychopharmacology, and different systems in medicine and psychiatry for handling reimbursement and patient records. For psychiatry residency training, recommendations focus on expanding neuroscience/neuropsychiatry faculty and integrating neuroscience education throughout the curriculum.Psychiatry traditionally concerns itself with helping individuals construct meaningful life narratives. Brain function is one of the fundamental determinants of individuality. It is now possible for psychiatrists to integrate knowledge of neuroscience into understanding the whole person by asking, What person has this brain? How does this brain make this person unique? How does this brain make this disorder unique? What treatment will help this disorder in this person with this brain?

Development of and Clinical Experience with a Simple Device for Performing Intraoperative Fluorescein Fluorescence Cerebral Angiography: Technical Notes.

PubMed

Ichikawa, Tsuyoshi; Suzuki, Kyouichi; Watanabe, Yoichi; Sato, Taku; Sakuma, Jun; Saito, Kiyoshi

2016-01-01

To perform intraoperative fluorescence angiography (FAG) under a microscope without an integrated FAG function with reasonable cost and sufficient quality for evaluation, we made a small and easy to use device for fluorescein FAG (FAG filter). We investigated the practical use of this FAG filter during aneurysm surgery, revascularization surgery, and brain tumor surgery. The FAG filter consists of two types of filters: an excitatory filter and a barrier filter. The excitatory filter excludes all wavelengths except for blue light and the barrier filter passes long waves except for blue light. By adding this FAG filter to a microscope without an integrated FAG function, light from the microscope illuminating the surgical field becomes blue, which is blocked by the barrier filter. We put the FAG filter on the objective lens of the operating microscope correctly and fluorescein sodium was injected intravenously or intra-arterially. Fluorescence (green light) from vessels in the surgical field and the dyed tumor were clearly observed through the microscope and recorded by a memory device. This method was easy and could be performed in a short time (about 10 seconds). Blood flow of small vessels deep in the surgical field could be observed. Blood flow stagnation could be evaluated. However, images from this method were inferior to those obtained by currently commercially available microscopes with an integrated FAG function. In brain tumor surgery, a stained tumor on the brain surface could be observed using this method. FAG could be performed with a microscope without an integrated FAG function easily with only this FAG filter.

Development of and Clinical Experience with a Simple Device for Performing Intraoperative Fluorescein Fluorescence Cerebral Angiography: Technical Notes

PubMed Central

ICHIKAWA, Tsuyoshi; SUZUKI, Kyouichi; WATANABE, Yoichi; SATO, Taku; SAKUMA, Jun; SAITO, Kiyoshi

2016-01-01

To perform intraoperative fluorescence angiography (FAG) under a microscope without an integrated FAG function with reasonable cost and sufficient quality for evaluation, we made a small and easy to use device for fluorescein FAG (FAG filter). We investigated the practical use of this FAG filter during aneurysm surgery, revascularization surgery, and brain tumor surgery. The FAG filter consists of two types of filters: an excitatory filter and a barrier filter. The excitatory filter excludes all wavelengths except for blue light and the barrier filter passes long waves except for blue light. By adding this FAG filter to a microscope without an integrated FAG function, light from the microscope illuminating the surgical field becomes blue, which is blocked by the barrier filter. We put the FAG filter on the objective lens of the operating microscope correctly and fluorescein sodium was injected intravenously or intra-arterially. Fluorescence (green light) from vessels in the surgical field and the dyed tumor were clearly observed through the microscope and recorded by a memory device. This method was easy and could be performed in a short time (about 10 seconds). Blood flow of small vessels deep in the surgical field could be observed. Blood flow stagnation could be evaluated. However, images from this method were inferior to those obtained by currently commercially available microscopes with an integrated FAG function. In brain tumor surgery, a stained tumor on the brain surface could be observed using this method. FAG could be performed with a microscope without an integrated FAG function easily with only this FAG filter. PMID:26597335

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

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

Brain networks engaged in audiovisual integration during speech perception revealed by persistent homology-based network filtration.

PubMed

Kim, Heejung; Hahm, Jarang; Lee, Hyekyoung; Kang, Eunjoo; Kang, Hyejin; Lee, Dong Soo

2015-05-01

The human brain naturally integrates audiovisual information to improve speech perception. However, in noisy environments, understanding speech is difficult and may require much effort. Although the brain network is supposed to be engaged in speech perception, it is unclear how speech-related brain regions are connected during natural bimodal audiovisual or unimodal speech perception with counterpart irrelevant noise. To investigate the topological changes of speech-related brain networks at all possible thresholds, we used a persistent homological framework through hierarchical clustering, such as single linkage distance, to analyze the connected component of the functional network during speech perception using functional magnetic resonance imaging. For speech perception, bimodal (audio-visual speech cue) or unimodal speech cues with counterpart irrelevant noise (auditory white-noise or visual gum-chewing) were delivered to 15 subjects. In terms of positive relationship, similar connected components were observed in bimodal and unimodal speech conditions during filtration. However, during speech perception by congruent audiovisual stimuli, the tighter couplings of left anterior temporal gyrus-anterior insula component and right premotor-visual components were observed than auditory or visual speech cue conditions, respectively. Interestingly, visual speech is perceived under white noise by tight negative coupling in the left inferior frontal region-right anterior cingulate, left anterior insula, and bilateral visual regions, including right middle temporal gyrus, right fusiform components. In conclusion, the speech brain network is tightly positively or negatively connected, and can reflect efficient or effortful processes during natural audiovisual integration or lip-reading, respectively, in speech perception.

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

PubMed Central

Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

Thinking, Walking, Talking: Integratory Motor and Cognitive Brain Function

PubMed Central

Leisman, Gerry; Moustafa, Ahmed A.; Shafir, Tal

2016-01-01

In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID:27252937

Benefits of music training are widespread and lifelong: a bibliographic review of their non-musical effects.

PubMed

Dawson, William J

2014-06-01

Recent publications indicate that musical training has effects on non-musical activities, some of which are lifelong. This study reviews recent publications collected from the Performing Arts Medicine Association bibliography. Music training, whether instrumental or vocal, produces beneficial and long-lasting changes in brain anatomy and function. Anatomic changes occur in brain areas devoted to hearing, speech, hand movements, and coordination between both sides of the brain. Functional benefits include improved sound processing and motor skills, especially in the upper extremities. Training benefits extend beyond music skills, resulting in higher IQs and school grades, greater specialized sensory and auditory memory/recall, better language memory and processing, heightened bilateral hand motor functioning, and improved integration and synchronization of sensory and motor functions. These changes last long after music training ends and can minimize or prevent age-related loss of brain cells and some mental functions. Early institution of music training and prolonged duration of training both appear to contribute to these positive changes.

Reduced integration and differentiation of the imitation network in autism: A combined functional connectivity magnetic resonance imaging and diffusion-weighted imaging study.

PubMed

Fishman, Inna; Datko, Michael; Cabrera, Yuliana; Carper, Ruth A; Müller, Ralph-Axel

2015-12-01

Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms. Resting state functional magnetic resonance imaging and diffusion-weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion. Within-network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology. Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD. © 2015 American Neurological Association.

Brain-computer interface controlled functional electrical stimulation system for ankle movement.

PubMed

Do, An H; Wang, Po T; King, Christine E; Abiri, Ahmad; Nenadic, Zoran

2011-08-26

Many neurological conditions, such as stroke, spinal cord injury, and traumatic brain injury, can cause chronic gait function impairment due to foot-drop. Current physiotherapy techniques provide only a limited degree of motor function recovery in these individuals, and therefore novel therapies are needed. Brain-computer interface (BCI) is a relatively novel technology with a potential to restore, substitute, or augment lost motor behaviors in patients with neurological injuries. Here, we describe the first successful integration of a noninvasive electroencephalogram (EEG)-based BCI with a noninvasive functional electrical stimulation (FES) system that enables the direct brain control of foot dorsiflexion in able-bodied individuals. A noninvasive EEG-based BCI system was integrated with a noninvasive FES system for foot dorsiflexion. Subjects underwent computer-cued epochs of repetitive foot dorsiflexion and idling while their EEG signals were recorded and stored for offline analysis. The analysis generated a prediction model that allowed EEG data to be analyzed and classified in real time during online BCI operation. The real-time online performance of the integrated BCI-FES system was tested in a group of five able-bodied subjects who used repetitive foot dorsiflexion to elicit BCI-FES mediated dorsiflexion of the contralateral foot. Five able-bodied subjects performed 10 alternations of idling and repetitive foot dorsifiexion to trigger BCI-FES mediated dorsifiexion of the contralateral foot. The epochs of BCI-FES mediated foot dorsifiexion were highly correlated with the epochs of voluntary foot dorsifiexion (correlation coefficient ranged between 0.59 and 0.77) with latencies ranging from 1.4 sec to 3.1 sec. In addition, all subjects achieved a 100% BCI-FES response (no omissions), and one subject had a single false alarm. This study suggests that the integration of a noninvasive BCI with a lower-extremity FES system is feasible. With additional modifications, the proposed BCI-FES system may offer a novel and effective therapy in the neuro-rehabilitation of individuals with lower extremity paralysis due to neurological injuries.

Multi-sensory integration in a small brain

NASA Astrophysics Data System (ADS)

Gepner, Ruben; Wolk, Jason; Gershow, Marc

Understanding how fluctuating multi-sensory stimuli are integrated and transformed in neural circuits has proved a difficult task. To address this question, we study the sensori-motor transformations happening in the brain of the Drosophila larva, a tractable model system with about 10,000 neurons. Using genetic tools that allow us to manipulate the activity of individual brain cells through their transparent body, we observe the stochastic decisions made by freely-behaving animals as their visual and olfactory environments fluctuate independently. We then use simple linear-nonlinear models to correlate outputs with relevant features in the inputs, and adaptive filtering processes to track changes in these relevant parameters used by the larva's brain to make decisions. We show how these techniques allow us to probe how statistics of stimuli from different sensory modalities combine to affect behavior, and can potentially guide our understanding of how neural circuits are anatomically and functionally integrated. Supported by NIH Grant 1DP2EB022359 and NSF Grant PHY-1455015.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

PubMed

Zamroziewicz, Marta K; Barbey, Aron K

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

PubMed Central

Zamroziewicz, Marta K.; Barbey, Aron K.

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

Using Both Sides of the Brain: Experiences that Integrate Art and Talk Therapy Through Scribble Drawings

ERIC Educational Resources Information Center

McNamee, Carole M.

2004-01-01

Neuroscience researchers identify a cerebral cortex with two functioning hemispheres: a left hemisphere associated with language and speech and a right hemisphere associated with visual-motor activities. Additionally, neuroscientists argue that contemporary lifestyles favor the verbal, logical left brain and often ignore the truths that present in…

COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.

PubMed

Nevalainen, N; Riklund, K; Andersson, M; Axelsson, J; Ögren, M; Lövdén, M; Lindenberger, U; Bäckman, L; Nyberg, L

2015-07-01

Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions.

PubMed

Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G; Hoffman, Jared D; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M S; Lin, Ai-Ling

2016-11-08

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

PubMed Central

Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

2016-01-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?

PubMed Central

Ochoa-Repáraz, Javier; Kasper, Lloyd H.

2016-01-01

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior. PMID:26865085

The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?

PubMed

Ochoa-Repáraz, Javier; Kasper, Lloyd H

2016-03-01

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior.

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

PubMed

Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne Yw; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

2016-03-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

Ontogenetic ritualization of primate gesture as a case study in dyadic brain modeling.

PubMed

Gasser, Brad; Cartmill, Erica A; Arbib, Michael A

2014-01-01

This paper introduces dyadic brain modeling - the simultaneous, computational modeling of the brains of two interacting agents - to explore ways in which our understanding of macaque brain circuitry can ground new models of brain mechanisms involved in ape interaction. Specifically, we assess a range of data on gestural communication of great apes as the basis for developing an account of the interactions of two primates engaged in ontogenetic ritualization, a proposed learning mechanism through which a functional action may become a communicative gesture over repeated interactions between two individuals (the 'dyad'). The integration of behavioral, neural, and computational data in dyadic (or, more generally, social) brain modeling has broad application to comparative and evolutionary questions, particularly for the evolutionary origins of cognition and language in the human lineage. We relate this work to the neuroinformatics challenges of integrating and sharing data to support collaboration between primatologists, neuroscientists and modelers that will help speed the emergence of what may be called comparative neuro-primatology.

Seeking Synthesis: The Integrative Problem in Understanding Language and Its Evolution.

PubMed

Dale, Rick; Kello, Christopher T; Schoenemann, P Thomas

2016-04-01

We discuss two problems for a general scientific understanding of language, sequences and synergies: how language is an intricately sequenced behavior and how language is manifested as a multidimensionally structured behavior. Though both are central in our understanding, we observe that the former tends to be studied more than the latter. We consider very general conditions that hold in human brain evolution and its computational implications, and identify multimodal and multiscale organization as two key characteristics of emerging cognitive function in our species. This suggests that human brains, and cognitive function specifically, became more adept at integrating diverse information sources and operating at multiple levels for linguistic performance. We argue that framing language evolution, learning, and use in terms of synergies suggests new research questions, and it may be a fruitful direction for new developments in theory and modeling of language as an integrated system. Copyright © 2016 Cognitive Science Society, Inc.

Effect of meditation on psychological distress and brain functioning: A randomized controlled study.

PubMed

Travis, Fred; Valosek, Laurent; Konrad, Arthur; Link, Janice; Salerno, John; Scheller, Ray; Nidich, Sanford

2018-06-21

Psychological stability and brain integration are important factors related to physical and mental health and organization effectiveness. This study tested whether a mind-body technique, the Transcendental Meditation (TM) program could increase EEG brain integration and positive affect, and decrease psychological distress in government employees. Ninety-six central office administrators and staff at the San Francisco Unified School District were randomly assigned to either immediate start of the TM program or to a wait-list control group. At baseline and four-month posttest, participants completed an online version of the Profile of Mood States questionnaire (POMS). In addition, a subset of this population (N = 79) had their EEG recorded at baseline and at four-month posttest to calculate Brain Integration Scale (BIS) scores. At posttest, TM participants significantly decreased on the POMS Total Mood Disturbance and anxiety, anger, depression, fatigue, and confusion subscales, and significantly increased in the POMS vigor subscale. TM participants in the EEG-subgroup also significantly increased in BIS scores. Compliance with meditation practice was high (93%). Findings indicate the feasibility and effectiveness of implementing the TM program to improve brain integration and positive affect and reduce psychological distress in government administrators and staff. Copyright © 2018. Published by Elsevier Inc.

Sleep and Psychiatric Disorders in Persons With Mild Traumatic Brain Injury.

PubMed

Mollayeva, Tatyana; D'Souza, Andrea; Mollayeva, Shirin

2017-08-01

Mild traumatic brain injury (mTBI) frequently challenges the integrity of sleep function by affecting multiple brain areas implicated in controlling the switch between wakefulness and sleep and those involved in circadian and homeostatic processes; the malfunction of each causes a variety of disorders. In this review, we discuss recent data on the dynamics between disorders of sleep and mental/psychiatric disorders in persons with mTBI. This analysis sets the stage for understanding how a variety of physiological, emotional and environmental influences affect sleep and mental activities after injury to the brain. Consideration of the intricate links between sleep and mental functions in future research can increase understanding on the underlying mechanisms of sleep-related and psychiatric comorbidity in mTBI.

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

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

2015-01-01

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

Similarity-Based Fusion of MEG and fMRI Reveals Spatio-Temporal Dynamics in Human Cortex During Visual Object Recognition

PubMed Central

Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2016-01-01

Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG–fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50–80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG–fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions. PMID:27235099

Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

PubMed Central

Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

2014-01-01

Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

Enlarging the scope: grasping brain complexity

PubMed Central

Tognoli, Emmanuelle; Kelso, J. A. Scott

2014-01-01

To further advance our understanding of the brain, new concepts and theories are needed. In particular, the ability of the brain to create information flows must be reconciled with its propensity for synchronization and mass action. The theoretical and empirical framework of Coordination Dynamics, a key aspect of which is metastability, are presented as a starting point to study the interplay of integrative and segregative tendencies that are expressed in space and time during the normal course of brain and behavioral function. Some recent shifts in perspective are emphasized, that may ultimately lead to a better understanding of brain complexity. PMID:25009476

The multisensory brain and its ability to learn music.

PubMed

Zimmerman, Emily; Lahav, Amir

2012-04-01

Playing a musical instrument requires a complex skill set that depends on the brain's ability to quickly integrate information from multiple senses. It has been well documented that intensive musical training alters brain structure and function within and across multisensory brain regions, supporting the experience-dependent plasticity model. Here, we argue that this experience-dependent plasticity occurs because of the multisensory nature of the brain and may be an important contributing factor to musical learning. This review highlights key multisensory regions within the brain and discusses their role in the context of music learning and rehabilitation. © 2012 New York Academy of Sciences.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

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.

The changing landscape of functional brain networks for face processing in typical development.

PubMed

Joseph, Jane E; Swearingen, Joshua E; Clark, Jonathan D; Benca, Chelsie E; Collins, Heather R; Corbly, Christine R; Gathers, Ann D; Bhatt, Ramesh S

2012-11-15

Greater expertise for faces in adults than in children may be achieved by a dynamic interplay of functional segregation and integration of brain regions throughout development. The present study examined developmental changes in face network functional connectivity in children (5-12 years) and adults (18-43 years) during face-viewing using a graph-theory approach. A face-specific developmental change involved connectivity of the right occipital face area. During childhood, this node increased in strength and within-module clustering based on positive connectivity. These changes reflect an important role of the ROFA in segregation of function during childhood. In addition, strength and diversity of connections within a module that included primary visual areas (left and right calcarine) and limbic regions (left hippocampus and right inferior orbitofrontal cortex) increased from childhood to adulthood, reflecting increased visuo-limbic integration. This integration was pronounced for faces but also emerged for natural objects. Taken together, the primary face-specific developmental changes involved segregation of a posterior visual module during childhood, possibly implicated in early stage perceptual face processing, and greater integration of visuo-limbic connections from childhood to adulthood, which may reflect processing related to development of perceptual expertise for individuation of faces and other visually homogenous categories. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Co-activation patterns in resting-state fMRI signals.

PubMed

Liu, Xiao; Zhang, Nanyin; Chang, Catie; Duyn, Jeff H

2018-02-08

The brain is a complex system that integrates and processes information across multiple time scales by dynamically coordinating activities over brain regions and circuits. Correlations in resting-state functional magnetic resonance imaging (rsfMRI) signals have been widely used to infer functional connectivity of the brain, providing a metric of functional associations that reflects a temporal average over an entire scan (typically several minutes or longer). Not until recently was the study of dynamic brain interactions at much shorter time scales (seconds to minutes) considered for inference of functional connectivity. One method proposed for this objective seeks to identify and extract recurring co-activation patterns (CAPs) that represent instantaneous brain configurations at single time points. Here, we review the development and recent advancement of CAP methodology and other closely related approaches, as well as their applications and associated findings. We also discuss the potential neural origins and behavioral relevance of CAPs, along with methodological issues and future research directions in the analysis of fMRI co-activation patterns. Copyright © 2018 Elsevier Inc. All rights reserved.

[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.

Controllability of structural brain networks

NASA Astrophysics Data System (ADS)

Gu, Shi; Pasqualetti, Fabio; Cieslak, Matthew; Telesford, Qawi K.; Yu, Alfred B.; Kahn, Ari E.; Medaglia, John D.; Vettel, Jean M.; Miller, Michael B.; Grafton, Scott T.; Bassett, Danielle S.

2015-10-01

Cognitive function is driven by dynamic interactions between large-scale neural circuits or networks, enabling behaviour. However, fundamental principles constraining these dynamic network processes have remained elusive. Here we use tools from control and network theories to offer a mechanistic explanation for how the brain moves between cognitive states drawn from the network organization of white matter microstructure. Our results suggest that densely connected areas, particularly in the default mode system, facilitate the movement of the brain to many easily reachable states. Weakly connected areas, particularly in cognitive control systems, facilitate the movement of the brain to difficult-to-reach states. Areas located on the boundary between network communities, particularly in attentional control systems, facilitate the integration or segregation of diverse cognitive systems. Our results suggest that structural network differences between cognitive circuits dictate their distinct roles in controlling trajectories of brain network function.

Social Competence in Pediatric Brain Tumor Survivors: Application of a Model from Social Neuroscience and Developmental Psychology

PubMed Central

Hocking, Matthew C.; McCurdy, Mark; Turner, Elise; Kazak, Anne E.; Noll, Robert B.; Phillips, Peter; Barakat, Lamia P.

2014-01-01

Pediatric brain tumor (BT) survivors are at risk for psychosocial late effects across many domains of functioning, including neurocognitive and social. The literature on the social competence of pediatric BT survivors is still developing and future research is needed that integrates developmental and cognitive neuroscience research methodologies to identify predictors of survivor social adjustment and interventions to ameliorate problems. This review discusses the current literature on survivor social functioning through a model of social competence in childhood brain disorder and suggests future directions based on this model. Interventions pursuing change in survivor social adjustment should consider targeting social ecological factors. PMID:25382825

HSP27 Protects the Blood-Brain Barrier Against Ischemia-Induced Loss of Integrity

PubMed Central

Leak, Rehana K.; Zhang, Lili; Stetler, R. Anne; Weng, Zhongfang; Li, Peiying; Atkins, G. Brandon; Gao, Yanqin; Chen, Jun

2014-01-01

Loss of integrity of the blood-brain barrier (BBB) in stroke victims initiates a devastating cascade of events including extravasation of blood-borne molecules, water, and inflammatory cells deep into brain parenchyma. Thus, it is important to identify mechanisms by which BBB integrity can be maintained in the face of ischemic injury in experimental stroke. We previously demonstrated that the phylogenetically conserved small heat shock protein 27 (HSP27) protects against transient middle cerebral artery occlusion (tMCAO). Here we show that HSP27 transgenic overexpression also maintains the integrity of the BBB in mice subjected to tMCAO. Extravasation of endogenous IgG antibodies and exogenous FITC-albumin into the brain following tMCAO was reduced in transgenic mice, as was total brain water content. HSP27 overexpression abolished the appearance of TUNEL-positive profiles in microvessel walls. Transgenics also exhibited less loss of microvessel proteins following tMCAO. Notably, primary endothelial cell cultures were rescued from oxygen-glucose deprivation (OGD) by lentiviral HSP27 overexpression according to four viability assays, supporting a direct effect on this cell type. Finally, HSP27 overexpression reduced the appearance of neutrophils in the brain and inhibited the secretion of five cytokines. These findings reveal a novel role for HSP27 in attenuating ischemia/reperfusion injury - the maintenance of BBB integrity. Endogenous upregulation of HSP27 after ischemia in wild-type animals may exert similar protective functions and warrants further investigation. Exogenous enhancement of HSP27 by rational drug design may lead to future therapies against a host of injuries, including but not limited to a harmful breach in brain vasculature. PMID:23469858

Freedom of Thought and Mental Integrity: The Moral Requirements for Any Neural Prosthesis

PubMed Central

Lavazza, Andrea

2018-01-01

There are many kinds of neural prostheses available or being researched today. In most cases they are intended to cure or improve the condition of patients affected by some cerebral deficiency. In other cases, their goal is to provide new means to maintain or improve an individual's normal performance. In all these circumstances, one of the possible risks is that of violating the privacy of brain contents (which partly coincide with mental contents) or of depriving individuals of full control over their thoughts (mental states), as the latter are at least partly detectable by new prosthetic technologies. Given the (ethical) premise that the absolute privacy and integrity of the most relevant part of one's brain data is (one of) the most valuable and inviolable human right(s), I argue that a (technical) principle should guide the design and regulation of new neural prostheses. The premise is justified by the fact that whatever the coercion, the threat or the violence undergone, the person can generally preserve a “private repository” of thought in which to defend her convictions and identity, her dignity, and autonomy. Without it, the person may end up in a state of complete subjection to other individuals. The following functional principle is that neural prostheses should be technically designed and built so as to prevent such outcomes. They should: (a) incorporate systems that can find and signal the unauthorized detection, alteration, and diffusion of brain data and brain functioning; (b) be able to stop any unauthorized detection, alteration, and diffusion of brain data. This should not only regard individual devices, but act as a general (technical) operating principle shared by all interconnected systems that deal with decoding brain activity and brain functioning. PMID:29515355

Integrative Biological Analysis For Neuropsychopharmacology

PubMed Central

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

2014-01-01

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

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

PubMed Central

Landoni, Verónica I.; Schierloh, Pablo; de Campos Nebel, Marcelo; Fernández, Gabriela C.; Calatayud, Cecilia; Lapponi, María J.; Isturiz, Martín A.

2012-01-01

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS. PMID:22479186

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

PubMed

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

Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year. Copyright © 2016 Elsevier Inc. All rights reserved.

A cellular perspective on brain energy metabolism and functional imaging.

PubMed

Magistretti, Pierre J; Allaman, Igor

2015-05-20

The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. Copyright © 2015 Elsevier Inc. All rights reserved.

Cocaine-Induced Neurodevelopmental Deficits and Underlying Mechanisms

PubMed Central

Martin, Melissa M.; Graham, Devon L.; McCarthy, Deirdre M.; Bhide, Pradeep G.; Stanwood, Gregg D.

2017-01-01

Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. PMID:27345015

Hyperbrain features of team mental models within a juggling paradigm: a proof of concept

PubMed Central

Filho, Edson; Tamburro, Gabriella; Schinaia, Lorenzo; Chatel-Goldman, Jonas; di Fronso, Selenia; Robazza, Claudio

2016-01-01

Background Research on cooperative behavior and the social brain exists, but little research has focused on real-time motor cooperative behavior and its neural correlates. In this proof of concept study, we explored the conceptual notion of shared and complementary mental models through EEG mapping of two brains performing a real-world interactive motor task of increasing difficulty. We used the recently introduced participative “juggling paradigm,” and collected neuro-physiological and psycho-social data. We were interested in analyzing the between-brains coupling during a dyadic juggling task, and in exploring the relationship between the motor task execution, the jugglers’skill level and the task difficulty. We also investigated how this relationship could be mirrored in the coupled functional organization of the interacting brains. Methods To capture the neural schemas underlying the notion of shared and complementary mental models, we examined the functional connectivity patterns and hyperbrain features of a juggling dyad involved in cooperative motor tasks of increasing difficulty. Jugglers’ cortical activity was measured using two synchronized 32-channel EEG systems during dyadic juggling performed with 3, 4, 5 and 6 balls. Individual and hyperbrain functional connections were quantified through coherence maps calculated across all electrode pairs in the theta and alpha bands (4–8 and 8–12 Hz). Graph metrics were used to typify the global topology and efficiency of the functional networks for the four difficulty levels in the theta and alpha bands. Results Results indicated that, as task difficulty increased, the cortical functional organization of the more skilled juggler became progressively more segregated in both frequency bands, with a small-world organization in the theta band during easier tasks, indicative of a flow-like state in line with the neural efficiency hypothesis. Conversely, more integrated functional patterns were observed for the less skilled juggler in both frequency bands, possibly related to cognitive overload due to the difficulty of the task at hand (reinvestment hypothesis). At the hyperbrain level, a segregated functional organization involving areas of the visuo-attentional networks of both jugglers was observed in both frequency bands and for the easier task only. Discussion These results suggest that cooperative juggling is supported by integrated activity of specialized cortical areas from both brains only during easier tasks, whereas it relies on individual skills, mirrored in uncorrelated individual brain activations, during more difficult tasks. These findings suggest that task difficulty and jugglers’ personal skills may influence the features of the hyperbrain network in its shared/integrative and complementary/segregative tendencies. PMID:27688968

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.

Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

PubMed Central

Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

2016-01-01

Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

Forthergillian Lecture. Imaging human brain function.

PubMed

Frackowiak, R S

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Integration of the InTime Technique in the Neurodynamic Program of Assistance to Children with Learning Disabilities

ERIC Educational Resources Information Center

Ratner, Faina Lazarevna; Efimova, Victoria Leonidovna; Efimov, Oleg Igorevich

2015-01-01

The article describes the results of application of the "inTime" neuroacoustic training by Advanced Brain Technologies (USA) when they were organizing assistance to children who had learning disabilities. This training optimizes the functional state of the brain by using sounds of various frequency and rhythm. The effectiveness of the…

Expressive Art for the Social and Community Integration of Adolescents with Acquired Brain Injuries: A Systematic Review

ERIC Educational Resources Information Center

Goyal, Anita; Keightley, Michelle L.

2008-01-01

Adolescents with acquired brain injuries suffer from social and community withdrawal that result in isolation from their peer groups. The review highlights the evidence of effectiveness of expressive art interventions in the form of theatre for populations with difficulties in physical, emotional, cognitive, or social functioning. A systematic…

Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers

DTIC Science & Technology

2014-08-01

increase in ROS levels as compared to control, and this increased in ROS formation was abrogated by the antioxidant uric acid , UA (Table 1). Table 1...presence of UA antioxidant, uric acid , indicating the involvement of ROS in loss of the HBMEC integrity. The functional changes paralleled enhanced

Fronto-parietal and cingulo-opercular network integrity and cognition in health and schizophrenia

PubMed Central

Sheffield, Julia M; Repovs, Grega; Harms, Michael P.; Carter, Cameron S.; Gold, James M.; MacDonald, Angus W.; Ragland, J. Daniel; Silverstein, Steven M.; Godwin, Douglass; Barch, Deanna M

2015-01-01

Growing evidence suggests that coordinated activity within specific functional brain networks supports cognitive ability, and that abnormalities in brain connectivity may underlie cognitive deficits observed in neuropsychiatric diseases, such as schizophrenia. Two functional networks, the fronto-parietal network (FPN) and cingulo-opercular network (CON), are hypothesized to support top-down control of executive functioning, and have therefore emerged as potential drivers of cognitive impairment in disease-states. Graph theoretic analyses of functional connectivity data can characterize network topology, allowing the relationships between cognitive ability and network integrity to be examined. In the current study we applied graph analysis to pseudo-resting state data in 54 healthy subjects and 46 schizophrenia patients, and measured overall cognitive ability as the shared variance in performance from tasks of episodic memory, verbal memory, processing speed, goal maintenance, and visual integration. We found that, across all participants, cognitive ability was significantly positively associated with the local and global efficiency of the whole brain, FPN, and CON, but not with the efficiency of a comparison network, the auditory network. Additionally, the participation coefficient of the right anterior insula, a major hub within the CON, significantly predicted cognition, and this relationship was independent of CON global efficiency. Surprisingly, we did not observe strong evidence for group differences in any of our network metrics. These data suggest that functionally efficient task control networks support better cognitive ability in both health and schizophrenia, and that the right anterior insula may be a particularly important hub for successful cognitive performance across both health and disease. PMID:25979608

Automated voxel classification used with atlas-guided diffuse optical tomography for assessment of functional brain networks in young and older adults.

PubMed

Li, Lin; Cazzell, Mary; Babawale, Olajide; Liu, Hanli

2016-10-01

Atlas-guided diffuse optical tomography (atlas-DOT) is a computational means to image changes in cortical hemodynamic signals during human brain activities. Graph theory analysis (GTA) is a network analysis tool commonly used in functional neuroimaging to study brain networks. Atlas-DOT has not been analyzed with GTA to derive large-scale brain connectivity/networks based on near-infrared spectroscopy (NIRS) measurements. We introduced an automated voxel classification (AVC) method that facilitated the use of GTA with atlas-DOT images by grouping unequal-sized finite element voxels into anatomically meaningful regions of interest within the human brain. The overall approach included volume segmentation, AVC, and cross-correlation. To demonstrate the usefulness of AVC, we applied reproducibility analysis to resting-state functional connectivity measurements conducted from 15 young adults in a two-week period. We also quantified and compared changes in several brain network metrics between young and older adults, which were in agreement with those reported by a previous positron emission tomography study. Overall, this study demonstrated that AVC is a useful means for facilitating integration or combination of atlas-DOT with GTA and thus for quantifying NIRS-based, voxel-wise resting-state functional brain networks.

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

Long term reshaping of language, sensory, and motor maps after glioma resection: a new parameter to integrate in the surgical strategy

PubMed Central

Duffau, H; Denvil, D; Capelle, L

2002-01-01

Objectives: To describe cortical reorganisation and the effects of glioma infiltration on local brain function in three patients who underwent two operations 12–24 months apart. Methods: Three patients who had no neurological deficit underwent two operations for low grade glioma, located in functionally important brain regions. During each operation, local brain function was characterised by electrical mapping and awake craniotomy. Results: Language or sensorimotor areas had been invaded by the tumour at the time of the first operation, leading to incomplete glioma removal in all cases. Because of a tumour recurrence, the patients were reoperated on between 12 and 24 months later. Functional reorganisation of the language, sensory, and motor maps was detected by electrical stimulation of the brain, and this allowed total glioma removal without neurological sequelae. Conclusions: These findings show that surgical resection of a glioma can lead to functional reorganisation in the peritumorous and infiltrated brain. It may be that this reorganisation is directly or indirectly caused by the surgical procedure. If this hypothesis is confirmed by other studies, the use of such brain plasticity potential could be used when planning surgical options in some patients with low grade glioma. Such a strategy could extend the limits of tumour resection in gliomas involving eloquent brain areas without causing permanent morbidity. PMID:11909913

Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder.

PubMed

Krause-Utz, Annegret; Frost, Rachel; Winter, Dorina; Elzinga, Bernet M

2017-01-01

Dissociation involves disruptions of usually integrated functions of consciousness, perception, memory, identity, and affect (e.g., depersonalization, derealization, numbing, amnesia, and analgesia). While the precise neurobiological underpinnings of dissociation remain elusive, neuroimaging studies in disorders, characterized by high dissociation (e.g., depersonalization/derealization disorder (DDD), dissociative identity disorder (DID), dissociative subtype of posttraumatic stress disorder (D-PTSD)), have provided valuable insight into brain alterations possibly underlying dissociation. Neuroimaging studies in borderline personality disorder (BPD), investigating links between altered brain function/structure and dissociation, are still relatively rare. In this article, we provide an overview of neurobiological models of dissociation, primarily based on research in DDD, DID, and D-PTSD. Based on this background, we review recent neuroimaging studies on associations between dissociation and altered brain function and structure in BPD. These studies are discussed in the context of earlier findings regarding methodological differences and limitations and concerning possible implications for future research and the clinical setting.

Peroxisomes in brain development and function☆

PubMed Central

Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

2016-01-01

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.

PubMed

Kanoski, Scott E; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L

2010-01-01

Cognitive impairment and Alzheimer's disease are linked with intake of a Western diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-day consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. These results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.

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

PubMed

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

2016-02-01

Reinforcement learning (RL) is a powerful concept underlying forms of associative learning governed by the use of a scalar reward signal, with learning taking place if expectations are violated. RL may be assessed using model-based and model-free approaches. Model-based reinforcement learning involves the amygdala, the hippocampus, and the orbitofrontal cortex (OFC). The model-free system involves the pedunculopontine-tegmental nucleus (PPTgN), the ventral tegmental area (VTA) and the ventral striatum (VS). Based on the functional connectivity of VS, model-free and model based RL systems center on the VS that by integrating model-free signals (received as reward prediction error) and model-based reward related input computes value. Using the concept of reinforcement learning agent we propose that the VS serves as the value function component of the RL agent. Regarding the model utilized for model-based computations we turned to the proactive brain concept, which offers an ubiquitous function for the default network based on its great functional overlap with contextual associative areas. Hence, by means of the default network the brain continuously organizes its environment into context frames enabling the formulation of analogy-based association that are turned into predictions of what to expect. The OFC integrates reward-related information into context frames upon computing reward expectation by compiling stimulus-reward and context-reward information offered by the amygdala and hippocampus, respectively. Furthermore we suggest that the integration of model-based expectations regarding reward into the value signal is further supported by the efferent of the OFC that reach structures canonical for model-free learning (e.g., the PPTgN, VTA, and VS). (c) 2016 APA, all rights reserved).

Integration of Functional Magnetic Resonance Imaging and Magnetoencephalography Functional Maps Into a CyberKnife Planning System: Feasibility Study for Motor Activity Localization and Dose Planning.

PubMed

De Martin, Elena; Duran, Dunja; Ghielmetti, Francesco; Visani, Elisa; Aquino, Domenico; Marchetti, Marcello; Sebastiano, Davide Rossi; Cusumano, Davide; Bruzzone, Maria Grazia; Panzica, Ferruccio; Fariselli, Laura

2017-12-01

Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications. Copyright © 2017 Elsevier Inc. All rights reserved.

The maturing architecture of the brain's default network

PubMed Central

Fair, Damien A.; Cohen, Alexander L.; Dosenbach, Nico U. F.; Church, Jessica A.; Miezin, Francis M.; Barch, Deanna M.; Raichle, Marcus E.; Petersen, Steven E.; Schlaggar, Bradley L.

2008-01-01

In recent years, the brain's “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators suggested that, the brain's default mode supports “self-referential” or “introspective” mental activity. Subsequently, regions of the default network have been more specifically related to the “internal narrative,” the “autobiographical self,” “stimulus independent thought,” “mentalizing,” and most recently “self-projection.” However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7–9 years old); over development, these regions integrate into a cohesive, interconnected network. PMID:18322013

Adolescent brain development in normality and psychopathology

PubMed Central

LUCIANA, MONICA

2014-01-01

Since this journal’s inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field’s most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled. PMID:24342843

Adolescent brain development in normality and psychopathology.

PubMed

Luciana, Monica

2013-11-01

Since this journal's inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical-cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology-context interactions, represent the field's most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled.

Dynamic functional connectivity: Promise, issues, and interpretations

PubMed Central

Hutchison, R. Matthew; Womelsdorf, Thilo; Allen, Elena A.; Bandettini, Peter A.; Calhoun, Vince D.; Corbetta, Maurizio; Penna, Stefania Della; Duyn, Jeff H.; Glover, Gary H.; Gonzalez-Castillo, Javier; Handwerker, Daniel A.; Keilholz, Shella; Kiviniemi, Vesa; Leopold, David A.; de Pasquale, Francesco; Sporns, Olaf; Walter, Martin; Chang, Catie

2013-01-01

The brain must dynamically integrate, coordinate, and respond to internal and external stimuli across multiple time scales. Non-invasive measurements of brain activity with fMRI have greatly advanced our understanding of the large-scale functional organization supporting these fundamental features of brain function. Conclusions from previous resting-state fMRI investigations were based upon static descriptions of functional connectivity (FC), and only recently studies have begun to capitalize on the wealth of information contained within the temporal features of spontaneous BOLD FC. Emerging evidence suggests that dynamic FC metrics may index changes in macroscopic neural activity patterns underlying critical aspects of cognition and behavior, though limitations with regard to analysis and interpretation remain. Here, we review recent findings, methodological considerations, neural and behavioral correlates, and future directions in the emerging field of dynamic FC investigations. PMID:23707587

Two distinct forms of functional lateralization in the human brain

PubMed Central

Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

2013-01-01

The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

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-injured patients. One limitation is that its results do not provide specific measures about the biophysical mechanism underlying TBI. Continued work in this field will hopefully see graph metrics used as biomarkers to provide more accurate diagnosis and help guide treatment at the individual patient level. Copyright © 2016. Published by Elsevier Inc.

Cortical brain connectivity evaluated by graph theory in dementia: a correlation study between functional and structural data.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Curcio, Giuseppe; Altavilla, Riccardo; Scrascia, Federica; Giambattistelli, Federica; Quattrocchi, Carlo Cosimo; Bramanti, Placido; Vernieri, Fabrizio; Rossini, Paolo Maria

2015-01-01

A relatively new approach to brain function in neuroscience is the "functional connectivity", namely the synchrony in time of activity in anatomically-distinct but functionally-collaborating brain regions. On the other hand, diffusion tensor imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based technique with the capability to detect brain structural connection with fractional anisotropy (FA) identification. FA decrease has been observed in the corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI abnormalities are thought to be associated with functional disconnections among cortical areas. This study aimed to investigate possible correlations between structural damage, measured by MRI-DTI, and functional abnormalities of brain integration, measured by characteristic path length detected in resting state EEG source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11 moderate AD). For each subject, undirected and weighted brain network was built to evaluate graph core measures. eLORETA lagged linear connectivity values were used as weight of the edges of the network. Results showed that callosal FA reduction is associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha path length. These findings suggest that "global" (average network shortest path length representing an index of how efficient is the information transfer between two parts of the network) functional measure can reflect the reduction of fiber connecting the two hemispheres as revealed by DTI analysis and also anticipate in time this structural loss.

The enigma of the dorsolateral pons as a migraine generator

PubMed Central

Borsook, D; Burstein, R

2013-01-01

In this editorial, we integrate improved understanding of functional and structural brain stem anatomy with lessons learned from other disciplines on brainstem function to provide an alternative interpretation to the data used to support the brainstem migraine generator theory. PMID:22798640

Fine-Granularity Functional Interaction Signatures for Characterization of Brain Conditions

PubMed Central

Hu, Xintao; Zhu, Dajiang; Lv, Peili; Li, Kaiming; Han, Junwei; Wang, Lihong; Shen, Dinggang; Guo, Lei; Liu, Tianming

2014-01-01

In the human brain, functional activity occurs at multiple spatial scales. Current studies on functional brain networks and their alterations in brain diseases via resting-state functional magnetic resonance imaging (rs-fMRI) are generally either at local scale (regionally confined analysis and inter-regional functional connectivity analysis) or at global scale (graph theoretic analysis). In contrast, inferring functional interaction at fine-granularity sub-network scale has not been adequately explored yet. Here our hypothesis is that functional interaction measured at fine-granularity subnetwork scale can provide new insight into the neural mechanisms of neurological and psychological conditions, thus offering complementary information for healthy and diseased population classification. In this paper, we derived fine-granularity functional interaction (FGFI) signatures in subjects with Mild Cognitive Impairment (MCI) and Schizophrenia by diffusion tensor imaging (DTI) and rsfMRI, and used patient-control classification experiments to evaluate the distinctiveness of the derived FGFI features. Our experimental results have shown that the FGFI features alone can achieve comparable classification performance compared with the commonly used inter-regional connectivity features. However, the classification performance can be substantially improved when FGFI features and inter-regional connectivity features are integrated, suggesting the complementary information achieved from the FGFI signatures. PMID:23319242

The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface System.

PubMed

Liu, Xilin; Zhang, Milin; Subei, Basheer; Richardson, Andrew G; Lucas, Timothy H; Van der Spiegel, Jan

2015-04-01

In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI) system is presented. The system integrates four battery-powered wireless devices for the implementation of a closed-loop sensorimotor neural interface, including a neural signal analyzer, a neural stimulator, a body-area sensor node and a graphic user interface implemented on the PC end. The neural signal analyzer features a four channel analog front-end with configurable bandpass filter, gain stage, digitization resolution, and sampling rate. The target frequency band is configurable from EEG to single unit activity. A noise floor of 4.69 μVrms is achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural feature extraction, spike detection, sensing-stimulating modulation, and compressed sensing measurement are realized in a central processing unit integrated in the analyzer. A flash memory card is also integrated in the analyzer. A 2-channel neural stimulator with a compliance voltage up to ± 12 V is included. The stimulator is capable of delivering unipolar or bipolar, charge-balanced current pulses with programmable pulse shape, amplitude, width, pulse train frequency and latency. A multi-functional sensor node, including an accelerometer, a temperature sensor, a flexiforce sensor and a general sensor extension port has been designed. A computer interface is designed to monitor, control and configure all aforementioned devices via a wireless link, according to a custom designed communication protocol. Wireless closed-loop operation between the sensory devices, neural stimulator, and neural signal analyzer can be configured. The proposed system was designed to link two sites in the brain, bridging the brain and external hardware, as well as creating new sensory and motor pathways for clinical practice. Bench test and in vivo experiments are performed to verify the functions and performances of the system.

A new neuroinformatics approach to personalized medicine in neurology: The Virtual Brain

PubMed Central

Falcon, Maria I.; Jirsa, Viktor; Solodkin, Ana

2017-01-01

Purpose of review An exciting advance in the field of neuroimaging is the acquisition and processing of very large data sets (so called ‘big data’), permitting large-scale inferences that foster a greater understanding of brain function in health and disease. Yet what we are clearly lacking are quantitative integrative tools to translate this understanding to the individual level to lay the basis for personalized medicine. Recent findings Here we address this challenge through a review on how the relatively new field of neuroinformatics modeling has the capacity to track brain network function at different levels of inquiry, from microscopic to macroscopic and from the localized to the distributed. In this context, we introduce a new and unique multiscale approach, The Virtual Brain (TVB), that effectively models individualized brain activity, linking large-scale (macroscopic) brain dynamics with biophysical parameters at the microscopic level. We also show how TVB modeling provides unique biological interpretable data in epilepsy and stroke. Summary These results establish the basis for a deliberate integration of computational biology and neuroscience into clinical approaches for elucidating cellular mechanisms of disease. In the future, this can provide the means to create a collection of disease-specific models that can be applied on the individual level to personalize therapeutic interventions. Video abstract http://links.lww.com/CONR/A41 PMID:27224088

Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

PubMed

Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

2011-10-01

To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

Frontal lobe connectivity and cognitive impairment in pediatric frontal lobe epilepsy.

PubMed

Braakman, Hilde M H; Vaessen, Maarten J; Jansen, Jacobus F A; Debeij-van Hall, Mariette H J A; de Louw, Anton; Hofman, Paul A M; Vles, Johan S H; Aldenkamp, Albert P; Backes, Walter H

2013-03-01

Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue-induced craving of smokers.

PubMed

Yuan, Kai; Yu, Dahua; Bi, Yanzhi; Wang, Ruonan; Li, Min; Zhang, Yajuan; Dong, Minghao; Zhai, Jinquan; Li, Yangding; Lu, Xiaoqi; Tian, Jie

2017-09-01

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed Central

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

2012-01-01

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

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

PubMed

Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877). These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Real-time interactive tractography analysis for multimodal brain visualization tool: MultiXplore

NASA Astrophysics Data System (ADS)

Bakhshmand, Saeed M.; de Ribaupierre, Sandrine; Eagleson, Roy

2017-03-01

Most debilitating neurological disorders can have anatomical origins. Yet unlike other body organs, the anatomy alone cannot easily provide an understanding of brain functionality. In fact, addressing the challenge of linking structural and functional connectivity remains in the frontiers of neuroscience. Aggregating multimodal neuroimaging datasets may be critical for developing theories that span brain functionality, global neuroanatomy and internal microstructures. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are main such techniques that are employed to investigate the brain under normal and pathological conditions. FMRI records blood oxygenation level of the grey matter (GM), whereas DTI is able to reveal the underlying structure of the white matter (WM). Brain global activity is assumed to be an integration of GM functional hubs and WM neural pathways that serve to connect them. In this study we developed and evaluated a two-phase algorithm. This algorithm is employed in a 3D interactive connectivity visualization framework and helps to accelerate clustering of virtual neural pathways. In this paper, we will detail an algorithm that makes use of an index-based membership array formed for a whole brain tractography file and corresponding parcellated brain atlas. Next, we demonstrate efficiency of the algorithm by measuring required times for extracting a variety of fiber clusters, which are chosen in such a way to resemble all sizes probable output data files that algorithm will generate. The proposed algorithm facilitates real-time visual inspection of neuroimaging data to further the discovery in structure-function relationship of the brain networks.

Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls

PubMed Central

Svatkova, Alena; Mandl, René C.W.; Scheewe, Thomas W.; Cahn, Wiepke; Kahn, René S.; Hulshoff Pol, Hilleke E.

2015-01-01

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. PMID:25829377

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

PubMed

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

2016-07-06

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

High-throughput screening for identification of blood-brain barrier integrity enhancers: a drug repurposing opportunity to rectify vascular amyloid toxicity

PubMed Central

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

2016-01-01

The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer’s disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76–4.56 μM. Of these 7 drugs, five were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD. PMID:27392852

Probing the brain with molecular fMRI.

PubMed

Ghosh, Souparno; Harvey, Peter; Simon, Jacob C; Jasanoff, Alan

2018-06-01

One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural processing. We discuss how a combination of innovative probe design, advanced imaging methods, and strategies for brain delivery can make molecular fMRI an increasingly successful approach for spatiotemporally resolved studies of diverse neural phenomena, perhaps eventually in people. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Nervous System and Gastrointestinal Function

ERIC Educational Resources Information Center

Altaf, Muhammad A.; Sood, Manu R.

2008-01-01

The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

High-density diffuse optical tomography of term infant visual cortex in the nursery

NASA Astrophysics Data System (ADS)

Liao, Steve M.; Ferradal, Silvina L.; White, Brian R.; Gregg, Nicholas; Inder, Terrie E.; Culver, Joseph P.

2012-08-01

Advancements in antenatal and neonatal medicine over the last few decades have led to significant improvement in the survival rates of sick newborn infants. However, this improvement in survival has not been matched by a reduction in neurodevelopmental morbidities with increasing recognition of the diverse cognitive and behavioral challenges that preterm infants face in childhood. Conventional neuroimaging modalities, such as cranial ultrasound and magnetic resonance imaging, provide an important definition of neuroanatomy with recognition of brain injury. However, they fail to define the functional integrity of the immature brain, particularly during this critical developmental period. Diffuse optical tomography methods have established success in imaging adult brain function; however, few studies exist to demonstrate their feasibility in the neonatal population. We demonstrate the feasibility of using recently developed high-density diffuse optical tomography (HD-DOT) to map functional activation of the visual cortex in healthy term-born infants. The functional images show high contrast-to-noise ratio obtained in seven neonates. These results illustrate the potential for HD-DOT and provide a foundation for investigations of brain function in more vulnerable newborns, such as preterm infants.

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

PubMed

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

2014-01-01

Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Methodological Problems on the Way to Integrative Human Neuroscience.

PubMed

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge , rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience , which will not only link different fields and levels, but also help in understanding clinical phenomena.

Methodological Problems on the Way to Integrative Human Neuroscience

PubMed Central

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A.; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge, rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience, which will not only link different fields and levels, but also help in understanding clinical phenomena. PMID:27965548

Long-term supratentorial brain structure and cognitive function following cerebellar tumour resections in childhood.

PubMed

Moberget, T; Andersson, S; Lundar, T; Due-Tønnessen, B J; Heldal, A; Endestad, T; Westlye, L T

2015-03-01

The cerebellum is connected to extensive regions of the cerebrum, and cognitive deficits following cerebellar lesions may thus be related to disrupted cerebello-cerebral connectivity. Moreover, early cerebellar lesions could affect distal brain development, effectively inducing long-term changes in brain structure and cognitive function. Here, we characterize supratentorial brain structure and cognitive function in 20 adult patients treated for cerebellar tumours in childhood (mean age at surgery: 7.1 years) and 26 matched controls. Relative to controls, patients showed reduced cognitive function and increased grey matter density in bilateral cingulum, left orbitofrontal cortex and the left hippocampus. Within the patient group, increased grey matter density in these regions was associated with decreased performance on tests of processing speed and executive function. Further, diffusion tensor imaging revealed widespread alterations in white matter microstructure in patients. While current ventricle volume (an index of previous hydrocephalus severity it patients) was associated with grey matter density and white matter microstructure in patients, this could only partially account for the observed group differences in brain structure and cognitive function. In conclusion, our results show distal effects of cerebellar lesions on cerebral integrity and wiring, likely caused by a combination of neurodegenerative processes and perturbed neurodevelopment. Copyright © 2015 Elsevier Ltd. All rights reserved.

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 disruption of brain connectivity among central hub regions of the brain, potentially leading to reduced communication capacity and altered functional brain dynamics.

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

The teen brain: insights from neuroimaging.

PubMed

Giedd, Jay N

2008-04-01

Few parents of a teenager are surprised to hear that the brain of a 16-year-old is different from the brain of an 8-year-old. Yet to pin down these differences in a rigorous scientific way has been elusive. Magnetic resonance imaging, with the capacity to provide exquisitely accurate quantifications of brain anatomy and physiology without the use of ionizing radiation, has launched a new era of adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, extending well into young adulthood. Although overinterpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the implications of these brain changes on cognition, emotion, and behavior.

Modulatory Effects of Dietary Amino Acids on Neurodegenerative Diseases.

PubMed

Rajagopal, Senthilkumar; Sangam, Supraj Raja; Singh, Shubham; Joginapally, Venkateswara Rao

2016-01-01

Proteins are playing a vital role in maintaining the cellular integrity and function, as well as for brain cells. Protein intake and supplementation of individual amino acids can affect the brain functioning and mental health, and many of the neurotransmitters in the brain are made from amino acids. The amino acid supplementation has been found to reduce symptoms, as they are converted into neurotransmitters which in turn extenuate the mental disorders. The biosynthesis of amino acids in the brain is regulated by the concentration of amino acids in plasma. The brain diseases such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD) are the most common mental disorders that are currently widespread in numerous countries. The intricate biochemical and molecular machinery contributing to the neurological disorders is still unknown, and in this chapter, we revealed the involvement of dietary amino acids on neurological diseases.

Clinical indications for high-field 1.5 T intraoperative magnetic resonance imaging and neuro-navigation for neurosurgical procedures. Review of initial 100 cases.

PubMed

Maesawa, Satoshi; Fujii, Masazumi; Nakahara, Norimoto; Watanabe, Tadashi; Saito, Kiyoshi; Kajita, Yasukazu; Nagatani, Tetsuya; Wakabayashi, Toshihiko; Yoshida, Jun

2009-08-01

Initial experiences are reviewed in an integrated operation theater equipped with an intraoperative high-field (1.5 T) magnetic resonance (MR) imager and neuro-navigation (BrainSUITE), to evaluate the indications and limitations. One hundred consecutive cases were treated, consisting of 38 gliomas, 49 other tumors, 11 cerebrovascular diseases, and 2 functional diseases. The feasibility and usefulness of the integrated theater were evaluated for individual diseases, focusing on whether intraoperative images (including diffusion tensor imaging) affected the surgical strategy. The extent of resection and outcomes in each histological category of brain tumors were examined. Intraoperative high-field MR imaging frequently affected or modified the surgical strategy in the glioma group (27/38 cases, 71.1%), but less in the other tumor group (13/49 cases, 26.5%). The surgical strategy was not modified in cerebrovascular or functional diseases, but the success of procedures and the absence of complications could be confirmed. In glioma surgery, subtotal or greater resection was achieved in 22 of the 31 patients (71%) excluding biopsies, and intraoperative images revealed tumor remnants resulting in the extension of resection in 21 of the 22 patients (95.4%), the highest rate of extension among all types of pathologies. The integrated neuro-navigation improved workflow. The best indication for intraoperative high-field MR imaging and integrated neuro-navigation is brain tumors, especially gliomas, and is supplementary in assuring quality in surgery for cerebrovascular or functional diseases. Immediate quality assurance is provided in several types of neurosurgical procedures.

Gliotransmitters travel in time and space.

PubMed

Araque, Alfonso; Carmignoto, Giorgio; Haydon, Philip G; Oliet, Stéphane H R; Robitaille, Richard; Volterra, Andrea

2014-02-19

The identification of the presence of active signaling between astrocytes and neurons in a process termed gliotransmission has caused a paradigm shift in our thinking about brain function. However, we are still in the early days of the conceptualization of how astrocytes influence synapses, neurons, networks, and ultimately behavior. In this Perspective, our goal is to identify emerging principles governing gliotransmission and consider the specific properties of this process that endow the astrocyte with unique functions in brain signal integration. We develop and present hypotheses aimed at reconciling confounding reports and define open questions to provide a conceptual framework for future studies. We propose that astrocytes mainly signal through high-affinity slowly desensitizing receptors to modulate neurons and perform integration in spatiotemporal domains complementary to those of neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Executive functioning in TBI from rehabilitation to social reintegration: COMPASS (goal,) a randomized controlled trial (grant: 1I01RX000637-01A3 by the VA ORD RR&D, 2013-2016).

PubMed

Libin, Alexander V; Scholten, Joel; Schladen, Manon Maitland; Danford, Ellen; Shara, Nawar; Penk, Walter; Grafman, Jordan; Resnik, Linda; Bruner, Dwan; Cichon, Samantha; Philmon, Miriam; Tsai, Brenda; Blackman, Marc; Dromerick, Alexander

2015-01-01

Traumatic brain injury is a major health problem that frequently leads to deficits in executive function. Self-regulation processes, such as goal-setting, may become disordered after traumatic brain injury, particularly when the frontal regions of the brain and their connections are involved. Such impairments reduce injured veterans' ability to return to work or school and to regain satisfactory personal lives. Understanding the neurologically disabling effects of brain injury on executive function is necessary for both the accurate diagnosis of impairment and the individual tailoring of rehabilitation processes to help returning service members recover independent function. The COMPASS(goal) (Community Participation through Self-Efficacy Skills Development) program develops and tests a novel patient-centered intervention framework for community re-integration psychosocial research in veterans with mild traumatic brain injury. COMPASS(goal) integrates the principles and best practices of goal self-management. Goal setting is a core skill in self-management training by which persons with chronic health conditions learn to improve their status and decrease symptom effects. Over a three-year period, COMPASS(goal) will recruit 110 participants with residual executive dysfunction three months or more post-injury. Inclusion criteria combine both clinical diagnosis and standardized scores that are >1 SD from the normative score on the Frontal Systems Rating Scale. Participants are randomized into two groups: goal-management (intervention) and supported discharge (control). The intervention is administered in eight consecutive, weekly sessions. Assessments occur at enrollment, post-intervention/supported discharge, and three months post-treatment follow-up. Goal management is part of the "natural language" of rehabilitation. However, collaborative goal-setting between clinicians/case managers and clients can be hindered by the cognitive deficits that follow brain injury. Re-training returning veterans with brain injury in goal management, with appropriate help and support, would essentially treat deficits in executive function. A structured approach to goal self-management may foster greater independence and self-efficacy, help veterans gain insight into goals that are realistic for them at a given time, and help clinicians and veterans to work more effectively as true collaborators.

Traffic pollution exposure is associated with altered brain connectivity in school children.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

2016-04-01

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

Friends with social benefits: host-microbe interactions as a driver of brain evolution and development?

PubMed Central

Stilling, Roman M.; Bordenstein, Seth R.; Dinan, Timothy G.; Cryan, John F.

2014-01-01

The tight association of the human body with trillions of colonizing microbes that we observe today is the result of a long evolutionary history. Only very recently have we started to understand how this symbiosis also affects brain function and behavior. In this hypothesis and theory article, we propose how host-microbe associations potentially influenced mammalian brain evolution and development. In particular, we explore the integration of human brain development with evolution, symbiosis, and RNA biology, which together represent a “social triangle” that drives human social behavior and cognition. We argue that, in order to understand how inter-kingdom communication can affect brain adaptation and plasticity, it is inevitable to consider epigenetic mechanisms as important mediators of genome-microbiome interactions on an individual as well as a transgenerational time scale. Finally, we unite these interpretations with the hologenome theory of evolution. Taken together, we propose a tighter integration of neuroscience fields with host-associated microbiology by taking an evolutionary perspective. PMID:25401092

Long-Term Ability to Interpret Facial Expression after Traumatic Brain Injury and Its Relation to Social Integration

ERIC Educational Resources Information Center

Knox, Lucy; Douglas, Jacinta

2009-01-01

There is considerable evidence that individuals with traumatic brain injury (TBI) experience problems interpreting the emotional state of others. However, the functional implications of these changes have not been fully investigated. A study of 13 individuals with severe TBI and an equal number of matched controls found that TBI participants had…

Bipolar disorder: a neural network perspective on a disorder of emotion and motivation.

PubMed

Wessa, Michèle; Kanske, Philipp; Linke, Julia

2014-01-01

Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.

Evaluating the effectiveness of reasoning training in military and civilian chronic traumatic brain injury patients: study protocol

PubMed Central

2013-01-01

Background Individuals who sustain traumatic brain injuries (TBIs) often continue to experience significant impairment of cognitive functions mediated by the prefrontal cortex well into chronic stages of recovery. Traditional brain training programs that focus on improving specific skills fall short of addressing integrative functions that draw upon multiple higher-order processes critical for social and vocational integration. In the current study, we compare the effects of two short-term, intensive, group-based cognitive rehabilitation programs for individuals with chronic TBI. One program emphasizes learning about brain functions and influences on cognition, while the other program adopts a top-down approach to improve abstract reasoning abilities that are largely reliant on the prefrontal cortex. These treatment programs are evaluated in civilian and military veteran TBI populations. Methods/design One hundred individuals are being enrolled in this double-blinded clinical trial (all measures and data analyses will be conducted by blinded raters and analysts). Each individual is randomly assigned to one of two treatment conditions, with each condition run in groups of five to seven individuals. The primary anticipated outcomes are improvement in abstract reasoning and everyday life functioning, measured through behavioral tasks and questionnaires, and attention modulation, as measured by functional neuroimaging. Secondary expected outcomes include improvements in the cognitive processes of working memory, attention, and inhibitory control. Discussion Results of this trial will determine whether cognitive rehabilitation aimed at teaching TBI-relevant information about the brain and cognition versus training in TBI-affected thinking abilities (e.g., memory, attention, and executive functioning) can improve outcomes in chronic military and civilian TBI patient populations. It should shed light on the nature of improvements and the characteristics of patients most likely to benefit. This trial will also provide information about the sustainability of treatment-related improvements 3 months post-training. Trial registration ClinicalTrials.gov Identifier: NCT01552473 PMID:23363480

Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

PubMed Central

Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G.; Hoffman, Jared D.; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M.S.; Lin, Ai-Ling

2016-01-01

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders. PMID:27829242

Intraoperative virtual brain counseling

NASA Astrophysics Data System (ADS)

Jiang, Zhaowei; Grosky, William I.; Zamorano, Lucia J.; Muzik, Otto; Diaz, Fernando

1997-06-01

Our objective is to offer online real-tim e intelligent guidance to the neurosurgeon. Different from traditional image-guidance technologies that offer intra-operative visualization of medical images or atlas images, virtual brain counseling goes one step further. It can distinguish related brain structures and provide information about them intra-operatively. Virtual brain counseling is the foundation for surgical planing optimization and on-line surgical reference. It can provide a warning system that alerts the neurosurgeon if the chosen trajectory will pass through eloquent brain areas. In order to fulfill this objective, tracking techniques are involved for intra- operativity. Most importantly, a 3D virtual brian environment, different from traditional 3D digitized atlases, is an object-oriented model of the brain that stores information about different brain structures together with their elated information. An object-oriented hierarchical hyper-voxel space (HHVS) is introduced to integrate anatomical and functional structures. Spatial queries based on position of interest, line segment of interest, and volume of interest are introduced in this paper. The virtual brain environment is integrated with existing surgical pre-planning and intra-operative tracking systems to provide information for planning optimization and on-line surgical guidance. The neurosurgeon is alerted automatically if the planned treatment affects any critical structures. Architectures such as HHVS and algorithms, such as spatial querying, normalizing, and warping are presented in the paper. A prototype has shown that the virtual brain is intuitive in its hierarchical 3D appearance. It also showed that HHVS, as the key structure for virtual brain counseling, efficiently integrates multi-scale brain structures based on their spatial relationships.This is a promising development for optimization of treatment plans and online surgical intelligent guidance.

Microstructural and functional connectivity in the developing preterm brain

PubMed Central

Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

2011-01-01

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Relationships among cognition, emotion, and motivation: implications for intervention and neuroplasticity in psychopathology.

PubMed

Crocker, Laura D; Heller, Wendy; Warren, Stacie L; O'Hare, Aminda J; Infantolino, Zachary P; Miller, Gregory A

2013-01-01

Emotion-cognition and motivation-cognition relationships and related brain mechanisms are receiving increasing attention in the clinical research literature as a means of understanding diverse types of psychopathology and improving biological and psychological treatments. This paper reviews and integrates some of the growing evidence for cognitive biases and deficits in depression and anxiety, how these disruptions interact with emotional and motivational processes, and what brain mechanisms appear to be involved. This integration sets the stage for understanding the role of neuroplasticity in implementing change in cognitive, emotional, and motivational processes in psychopathology as a function of intervention.

Mind Operational Semantics and Brain Operational Architectonics: A Putative Correspondence

PubMed Central

Benedetti, Giulio; Marchetti, Giorgio; Fingelkurts, Alexander A; Fingelkurts, Andrew A

2010-01-01

Despite allowing for the unprecedented visualization of brain functional activity, modern neurobiological techniques have not yet been able to provide satisfactory answers to important questions about the relationship between brain and mind. The aim of this paper is to show how two different but complementary approaches, Mind Operational Semantics (OS) and Brain Operational Architectonics (OA), can help bridge the gap between a specific kind of mental activity—the higher-order reflective thought or linguistic thought—and brain. The fundamental notion that allows the two different approaches to be jointly used under a common framework is that of operation. According to OS, which is based on introspection and linguistic data, the meanings of words can be analyzed in terms of elemental mental operations (EOMC), amongst which those of attention play a key role. Linguistic thought is made possible by special kinds of elements, which OS calls “correlators”, which have the function of tying together the other elements of thought, which OS calls “correlata” (a "correlational network” that is, a sentence, is so formed). Therefore, OS conceives of linguistic thought as a hierarchy of operations of increasing complexity. Likewise, according to OA, which is based on the joint analysis of cognitive and electromagnetic data (EEG and MEG), every conscious phenomenon is brought to existence by the joint operations of many functional and transient neuronal assemblies in the brain. According to OA, the functioning of the brain is always operational (made up of operations), and its structure is characterized by a hierarchy of operations of increasing complexity: single neurons, single assemblies of neurons, synchronized neuronal assemblies or Operational Modules (OM), integrated or complex OMs. The authors put forward the hypothesis that the whole level of OS’s description (EOMC, correlators, and correlational networks) corresponds to the level of OMs (or set of them) of different complexity within OA’s theory: EOMC could correspond to simple OMs, correlators to complex OMs and the correlational network to a set of simple and complex OMs. Finally, a set of experiments is proposed to verify the putative correspondence between OS and OA and prove the existence of an integrated continuum between brain and mind. PMID:21113277

Myelination, oligodendrocytes, and serious mental illness.

PubMed

Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

2014-11-01

Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. © 2014 Wiley Periodicals, Inc.

Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

PubMed

Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

2017-07-01

A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

Image-guided removal of supratentorial cavernomas in critical brain areas: application of neuronavigation and intraoperative magnetic resonance imaging.

PubMed

Gralla, J; Ganslandt, O; Kober, H; Buchfelder, M; Fahlbusch, R; Nimsky, C

2003-04-01

In a retrospective study the postoperative results of 26 patients operated on for supratentorial cavernous hemangiomas either deep-seated or near eloquent brain areas are summarized. An exact surgical approach to these lesions is essential to prevent neurological deterioration. Three different navigation systems were used and compared according to their clinical applicability. Complete removal of the lesion was obtained in all patients of this series. In six cases (23 %) functional data from magnetoencephalography or functional magnetic resonance imaging were integrated into the navigational setup. In 14 cases (54 %) intraoperative magnetic resonance imaging was performed. The follow-up time was 3 - 26 months (mean: 10 months). In the postoperative course one patient (3.8 %) developed a hemiparesis, another one developed quadrantopia. Nineteen patients presented with preoperative seizure history, 16 of these (84 %) had no further or rare seizures after surgery. The better results in seizure control were achieved in those patients with shorter duration of seizure history before surgery. The study indicates that the application of neuronavigation allows surgery on supratentorial cavernous hemangiomas in critical brain areas with low morbidity. The intraoperative visualization of eloquent cortex areas by integration of functional data allows a fast identification and exemption of eloquent brain areas, preventing neurological deterioration. Furthermore, the intraoperative MR resection control ensures a complete resection and illustrates the minimal invasive approach.

Functional Imaging and Related Techniques: An Introduction for Rehabilitation Researchers

PubMed Central

Crosson, Bruce; Ford, Anastasia; McGregor, Keith M.; Meinzer, Marcus; Cheshkov, Sergey; Li, Xiufeng; Walker-Batson, Delaina; Briggs, Richard W.

2010-01-01

Functional neuroimaging and related neuroimaging techniques are becoming important tools for rehabilitation research. Functional neuroimaging techniques can be used to determine the effects of brain injury or disease on brain systems related to cognition and behavior and to determine how rehabilitation changes brain systems. These techniques include: functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG), magnetoencephalography (MEG), near infrared spectroscopy (NIRS), and transcranial magnetic stimulation (TMS). Related diffusion weighted magnetic resonance imaging techniques (DWI), including diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI), can quantify white matter integrity. With the proliferation of these imaging techniques in rehabilitation research, it is critical that rehabilitation researchers, as well as consumers of rehabilitation research, become familiar with neuroimaging techniques, what they can offer, and their strengths and weaknesses The purpose to this review is to provide such an introduction to these neuroimaging techniques. PMID:20593321

Indications for quantum computation requirements from comparative brain analysis

NASA Astrophysics Data System (ADS)

Bernroider, Gustav; Baer, Wolfgang

2010-04-01

Whether or not neuronal signal properties can engage 'non-trivial', i.e. functionally significant, quantum properties, is the subject of an ongoing debate. Here we provide evidence that quantum coherence dynamics can play a functional role in ion conduction mechanism with consequences on the shape and associative character of classical membrane signals. In particular, these new perspectives predict that a specific neuronal topology (e.g. the connectivity pattern of cortical columns in the primate brain) is less important and not really required to explain abilities in perception and sensory-motor integration. Instead, this evidence is suggestive for a decisive role of the number and functional segregation of ion channel proteins that can be engaged in a particular neuronal constellation. We provide evidence from comparative brain studies and estimates of computational capacity behind visual flight functions suggestive for a possible role of quantum computation in biological systems.

The social brain in adolescence: Evidence from functional magnetic resonance imaging and behavioural studies

PubMed Central

Burnett, Stephanie; Sebastian, Catherine; Kadosh, Kathrin Cohen; Blakemore, Sarah-Jayne

2015-01-01

Social cognition is the collection of cognitive processes required to understand and interact with others. The term ‘social brain’ refers to the network of brain regions that underlies these processes. Recent evidence suggests that a number of social cognitive functions continue to develop during adolescence, resulting in age differences in tasks that assess cognitive domains including face processing, mental state inference and responding to peer influence and social evaluation. Concurrently, functional and structural magnetic resonance imaging (MRI) studies show differences between adolescent and adult groups within parts of the social brain. Understanding the relationship between these neural and behavioural observations is a challenge. This review discusses current research findings on adolescent social cognitive development and its functional MRI correlates, then integrates and interprets these findings in the context of hypothesised developmental neurocognitive and neurophysiological mechanisms. PMID:21036192

Lateral Information Processing by Spiking Neurons: A Theoretical Model of the Neural Correlate of Consciousness

PubMed Central

Ebner, Marc; Hameroff, Stuart

2011-01-01

Cognitive brain functions, for example, sensory perception, motor control and learning, are understood as computation by axonal-dendritic chemical synapses in networks of integrate-and-fire neurons. Cognitive brain functions may occur either consciously or nonconsciously (on “autopilot”). Conscious cognition is marked by gamma synchrony EEG, mediated largely by dendritic-dendritic gap junctions, sideways connections in input/integration layers. Gap-junction-connected neurons define a sub-network within a larger neural network. A theoretical model (the “conscious pilot”) suggests that as gap junctions open and close, a gamma-synchronized subnetwork, or zone moves through the brain as an executive agent, converting nonconscious “auto-pilot” cognition to consciousness, and enhancing computation by coherent processing and collective integration. In this study we implemented sideways “gap junctions” in a single-layer artificial neural network to perform figure/ground separation. The set of neurons connected through gap junctions form a reconfigurable resistive grid or sub-network zone. In the model, outgoing spikes are temporally integrated and spatially averaged using the fixed resistive grid set up by neurons of similar function which are connected through gap-junctions. This spatial average, essentially a feedback signal from the neuron's output, determines whether particular gap junctions between neurons will open or close. Neurons connected through open gap junctions synchronize their output spikes. We have tested our gap-junction-defined sub-network in a one-layer neural network on artificial retinal inputs using real-world images. Our system is able to perform figure/ground separation where the laterally connected sub-network of neurons represents a perceived object. Even though we only show results for visual stimuli, our approach should generalize to other modalities. The system demonstrates a moving sub-network zone of synchrony, within which the contents of perception are represented and contained. This mobile zone can be viewed as a model of the neural correlate of consciousness in the brain. PMID:22046178

The effect of repetitive subconcussive collisions on brain integrity in collegiate football players over a single football season: A multi-modal neuroimaging study.

PubMed

Slobounov, Semyon M; Walter, Alexa; Breiter, Hans C; Zhu, David C; Bai, Xiaoxiao; Bream, Tim; Seidenberg, Peter; Mao, Xianglun; Johnson, Brian; Talavage, Thomas M

2017-01-01

The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T 1 -weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant ( p  < 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant ( p  < 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates ( p  < 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.

Lateral information processing by spiking neurons: a theoretical model of the neural correlate of consciousness.

PubMed

Ebner, Marc; Hameroff, Stuart

2011-01-01

Cognitive brain functions, for example, sensory perception, motor control and learning, are understood as computation by axonal-dendritic chemical synapses in networks of integrate-and-fire neurons. Cognitive brain functions may occur either consciously or nonconsciously (on "autopilot"). Conscious cognition is marked by gamma synchrony EEG, mediated largely by dendritic-dendritic gap junctions, sideways connections in input/integration layers. Gap-junction-connected neurons define a sub-network within a larger neural network. A theoretical model (the "conscious pilot") suggests that as gap junctions open and close, a gamma-synchronized subnetwork, or zone moves through the brain as an executive agent, converting nonconscious "auto-pilot" cognition to consciousness, and enhancing computation by coherent processing and collective integration. In this study we implemented sideways "gap junctions" in a single-layer artificial neural network to perform figure/ground separation. The set of neurons connected through gap junctions form a reconfigurable resistive grid or sub-network zone. In the model, outgoing spikes are temporally integrated and spatially averaged using the fixed resistive grid set up by neurons of similar function which are connected through gap-junctions. This spatial average, essentially a feedback signal from the neuron's output, determines whether particular gap junctions between neurons will open or close. Neurons connected through open gap junctions synchronize their output spikes. We have tested our gap-junction-defined sub-network in a one-layer neural network on artificial retinal inputs using real-world images. Our system is able to perform figure/ground separation where the laterally connected sub-network of neurons represents a perceived object. Even though we only show results for visual stimuli, our approach should generalize to other modalities. The system demonstrates a moving sub-network zone of synchrony, within which the contents of perception are represented and contained. This mobile zone can be viewed as a model of the neural correlate of consciousness in the brain.

Cognitive impairment and associated loss in brain white microstructure in aircrew members exposed to engine oil fumes.

PubMed

Reneman, Liesbeth; Schagen, Sanne B; Mulder, Michel; Mutsaerts, Henri J; Hageman, Gerard; de Ruiter, Michiel B

2016-06-01

Cabin air in airplanes can be contaminated with engine oil contaminants. These contaminations may contain organophosphates (OPs) which are known neurotoxins to brain white matter. However, it is currently unknown if brain white matter in aircrew is affected. We investigated whether we could objectify cognitive complaints in aircrew and whether we could find a neurobiological substrate for their complaints. After medical ethical approval from the local institutional review board, informed consent was obtained from 12 aircrew (2 females, on average aged 44.4 years, 8,130 flying hours) with cognitive complaints and 11 well matched control subjects (2 females, 43.4 years, 233 flying hours). Depressive symptoms and self-reported cognitive symptoms were assessed, in addition to a neuropsychological test battery. State of the art Magnetic Resonance Imaging (MRI) techniques were administered that assess structural and functional changes, with a focus on white matter integrity. In aircrew we found significantly more self-reported cognitive complaints and depressive symptoms, and a higher number of tests scored in the impaired range compared to the control group. We observed small clusters in the brain in which white matter microstructure was affected. Also, we observed higher cerebral perfusion values in the left occipital cortex, and reduced brain activation on a functional MRI executive function task. The extent of cognitive impairment was strongly associated with white matter integrity, but extent of estimated number of flight hours was not associated with cognitive impairment nor with reductions in white matter microstructure. Defects in brain white matter microstructure and cerebral perfusion are potential neurobiological substrates for cognitive impairments and mood deficits reported in aircrew.

Assessment of higher level cognitive-communication functions in adolescents with ABI: Standardization of the student version of the functional assessment of verbal reasoning and executive strategies (S-FAVRES).

PubMed

MacDonald, Sheila

2016-01-01

Childhood acquired brain injuries can disrupt communication functions needed for success in school, work and social interaction. Cognitive-communication difficulties may not be apparent until adolescence, when academic, environmental and social-emotional demands increase. The Functional Assessment of Verbal Reasoning and Executive Strategies for Students (S-FAVRES) is a new activity-level measure of cognitive-communication skills in complex, contextual and integrative tasks that simulate real world communication challenges. It is hypothesized that S-FAVRES performance would differentiate adolescents with and without acquired brain injury (ABI) on scores for Accuracy, Rationale, Reasoning Subskills and Time. S-FAVRES was administered to 182 typically-developing (TD) and 57 adolescents with mild-to-severe ABI aged 12-19. Group differences, internal consistency, sensitivity, specificity, reliability and contributing factors to performance (age, gender, brain injury) were examined statistically. Those with ABI attained statistically lower Accuracy, Rationale and Reasoning sub-skills scores than their TD peers. Time scores were not significantly different. Performance trends were consistent across tasks, administrations, gender and age groups. Inter-rater reliability for scoring was acceptable. The S-FAVRES provides a reliable, functional and quantifiable measure of subtle cognitive-communication difficulties in adolescents that can assist speech-language pathologists in planning treatment and integration to school and real world communication.

Theta-Modulated Gamma-Band Synchronization Among Activated Regions During a Verb Generation Task

PubMed Central

Doesburg, Sam M.; Vinette, Sarah A.; Cheung, Michael J.; Pang, Elizabeth W.

2012-01-01

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4–8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing. PMID:22707946

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions

PubMed Central

Iriki, Atsushi; Taoka, Miki

2012-01-01

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language—the site of such integration seems to be the parietal and extending opercular cortices. PMID:22106423

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions.

PubMed

Iriki, Atsushi; Taoka, Miki

2012-01-12

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language--the site of such integration seems to be the parietal and extending opercular cortices.

Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

PubMed

Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

2016-04-01

Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

"She Was a Little Social Butterfly": A Qualitative Analysis of Parent Perception of Social Functioning in Adolescent and Young Adult Brain Tumor Survivors.

PubMed

Wilford, Justin; Buchbinder, David; Fortier, Michelle A; Osann, Kathryn; Shen, Violet; Torno, Lilibeth; Sender, Leonard S; Parsons, Susan K; Wenzel, Lari

Psychosocial sequelae of diagnosis and treatment for childhood brain tumor survivors are significant, yet little is known about their impact on adolescent and young adult (AYA) brain tumor survivors. Interviews were conducted with parents of AYA brain tumor survivors with a focus on social functioning. Semistructured interviews were conducted with English- and Spanish-speaking parents of AYA brain tumor survivors ≥10 years of age who were >2 years postdiagnosis, and analyzed using emergent themes theoretically integrated with a social neuroscience model of social competence. Twenty parents representing 19 survivors with a survivor mean age 15.7 ± 3.3 years and 10.1 ± 4.8 years postdiagnosis were interviewed. Several themes relevant to the social neuroscience social competence model emerged. First, parents' perceptions of their children's impaired social functioning corroborated the model, particularly with regard to poor social adjustment, social withdrawal, impaired social information processing, and developmentally inappropriate peer communication. Second, ongoing physical and emotional sequelae of central nervous system insults were seen by parents as adversely affecting social functioning among survivors. Third, a disrupted family environment and ongoing parent psychosocial distress were experienced as salient features of daily life. We document that the aforementioned framework is useful for understanding the social impact of diagnosis and treatment on AYA brain tumor survivorship. Moreover, the framework highlights areas of intervention that may enhance social functioning for AYA brain tumor survivors.

Computer-assisted identification and volumetric quantification of dynamic contrast enhancement in brain MRI: an interactive system

NASA Astrophysics Data System (ADS)

Wu, Shandong; Avgeropoulos, Nicholas G.; Rippe, David J.

2013-03-01

We present a dedicated segmentation system for tumor identification and volumetric quantification in dynamic contrast brain magnetic resonance (MR) scans. Our goal is to offer a practically useful tool at the end of clinicians in order to boost volumetric tumor assessment. The system is designed to work in an interactive mode such that maximizes the integration of computing capacity and clinical intelligence. We demonstrate the main functions of the system in terms of its functional flow and conduct preliminary validation using a representative pilot dataset. The system is inexpensive, user-friendly, easy to deploy and integrate with picture archiving and communication systems (PACS), and possible to be open-source, which enable it to potentially serve as a useful assistant for radiologists and oncologists. It is anticipated that in the future the system can be integrated into clinical workflow so that become routine available to help clinicians make more objective interpretations of treatment interventions and natural history of disease to best advocate patient needs.

A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia.

PubMed

Wojtalik, Jessica A; Smith, Matthew J; Keshavan, Matcheri S; Eack, Shaun M

2017-10-21

Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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.

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.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data.

PubMed

Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

2015-01-01

It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

PubMed Central

2015-01-01

Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779

Comparison of laterality index of upper and lower limb movement using brain activated fMRI

NASA Astrophysics Data System (ADS)

Harirchian, Mohammad Hossein; Oghabian, Mohammad Ali; Rezvanizadeh, Alireza; Bolandzadeh, Niousha

2008-03-01

Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions such as motor functions. This asymmetry maybe altered in some clinical conditions such as Multiple Sclerosis (MS). The aim of this study was to delineate the laterality differences for upper and lower limbs in healthy subjects to compare this pattern with subjects suffering from MS in advance. Hence 9 Male healthy subjects underwent fMRI assessment, while they were asked to move their limbs in a predetermined pattern. The results showed that hands movement activates the brain with a significant lateralization in pre-motor cortex in comparison with lower limb. Also, dominant hands activate brain more lateralized than the non-dominant hand. In addition, Left basal ganglia were observed to be activated regardless of the hand used, While, These patterns of Brain activation was not detected in lower limbs. We hypothesize that this difference might be attributed to this point that hand is usually responsible for precise and fine voluntary movements, whereas lower limb joints are mainly responsible for locomotion, a function integrating voluntary and automatic bilateral movements.

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study

PubMed Central

Raschpichler, Matthias; Straatman, Kees; Schroeter, Matthias Leopold; Arelin, Katrin; Schlögl, Haiko; Fritzsch, Dominik; Mende, Meinhard; Pampel, André; Böttcher, Yvonne; Stumvoll, Michael; Villringer, Arno; Mueller, Karsten

2013-01-01

Objectives To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design Cross-sectional, exploratory. Setting University Clinic, Integrative Research and Treatment Centre. Participants We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected. PMID:23355665

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

PubMed

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

2017-05-15

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

The "silent" imprint of musical training.

PubMed

Klein, Carina; Liem, Franziskus; Hänggi, Jürgen; Elmer, Stefan; Jäncke, Lutz

2016-02-01

Playing a musical instrument at a professional level is a complex multimodal task requiring information integration between different brain regions supporting auditory, somatosensory, motor, and cognitive functions. These kinds of task-specific activations are known to have a profound influence on both the functional and structural architecture of the human brain. However, until now, it is widely unknown whether this specific imprint of musical practice can still be detected during rest when no musical instrument is used. Therefore, we applied high-density electroencephalography and evaluated whole-brain functional connectivity as well as small-world topologies (i.e., node degree) during resting state in a sample of 15 professional musicians and 15 nonmusicians. As expected, musicians demonstrate increased intra- and interhemispheric functional connectivity between those brain regions that are typically involved in music perception and production, such as the auditory, the sensorimotor, and prefrontal cortex as well as Broca's area. In addition, mean connectivity within this specific network was positively related to musical skill and the total number of training hours. Thus, we conclude that musical training distinctively shapes intrinsic functional network characteristics in such a manner that its signature can still be detected during a task-free condition. Hum Brain Mapp 37:536-546, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Neural dynamics for landmark orientation and angular path integration

PubMed Central

Seelig, Johannes D.; Jayaraman, Vivek

2015-01-01

Summary Many animals navigate using a combination of visual landmarks and path integration. In mammalian brains, head direction cells integrate these two streams of information by representing an animal's heading relative to landmarks, yet maintaining their directional tuning in darkness based on self-motion cues. Here we use two-photon calcium imaging in head-fixed flies walking on a ball in a virtual reality arena to demonstrate that landmark-based orientation and angular path integration are combined in the population responses of neurons whose dendrites tile the ellipsoid body — a toroidal structure in the center of the fly brain. The population encodes the fly's azimuth relative to its environment, tracking visual landmarks when available and relying on self-motion cues in darkness. When both visual and self-motion cues are absent, a representation of the animal's orientation is maintained in this network through persistent activity — a potential substrate for short-term memory. Several features of the population dynamics of these neurons and their circular anatomical arrangement are suggestive of ring attractors — network structures proposed to support the function of navigational brain circuits. PMID:25971509

The modulatory effect of semantic familiarity on the audiovisual integration of face-name pairs.

PubMed

Li, Yuanqing; Wang, Fangyi; Huang, Biao; Yang, Wanqun; Yu, Tianyou; Talsma, Durk

2016-12-01

To recognize individuals, the brain often integrates audiovisual information from familiar or unfamiliar faces, voices, and auditory names. To date, the effects of the semantic familiarity of stimuli on audiovisual integration remain unknown. In this functional magnetic resonance imaging (fMRI) study, we used familiar/unfamiliar facial images, auditory names, and audiovisual face-name pairs as stimuli to determine the influence of semantic familiarity on audiovisual integration. First, we performed a general linear model analysis using fMRI data and found that audiovisual integration occurred for familiar congruent and unfamiliar face-name pairs but not for familiar incongruent pairs. Second, we decoded the familiarity categories of the stimuli (familiar vs. unfamiliar) from the fMRI data and calculated the reproducibility indices of the brain patterns that corresponded to familiar and unfamiliar stimuli. The decoding accuracy rate was significantly higher for familiar congruent versus unfamiliar face-name pairs (83.2%) than for familiar versus unfamiliar faces (63.9%) and for familiar versus unfamiliar names (60.4%). This increase in decoding accuracy was not observed for familiar incongruent versus unfamiliar pairs. Furthermore, compared with the brain patterns associated with facial images or auditory names, the reproducibility index was significantly improved for the brain patterns of familiar congruent face-name pairs but not those of familiar incongruent or unfamiliar pairs. Our results indicate the modulatory effect that semantic familiarity has on audiovisual integration. Specifically, neural representations were enhanced for familiar congruent face-name pairs compared with visual-only faces and auditory-only names, whereas this enhancement effect was not observed for familiar incongruent or unfamiliar pairs. Hum Brain Mapp 37:4333-4348, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation

PubMed Central

Farzan, Faranak; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.; Halko, Mark

2016-01-01

Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in. PMID:27009405

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

PubMed Central

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

1998-01-01

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

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function

PubMed Central

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D.

2009-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings. PMID:19834575

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function.

PubMed

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D

2008-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings.

Dorsomedial prefontal cortex supports spontaneous thinking per se.

PubMed

Raij, T T; Riekki, T J J

2017-06-01

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

NASA Astrophysics Data System (ADS)

Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

2012-02-01

Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report

PubMed Central

Liu, Xiaolin; Silverman, Alan; Kern, Mark; Ward, B. Douglas; Li, Shi-Jiang; Shaker, Reza; Sood, Manu R.

2015-01-01

Background The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (1) brain responses to visceral stimulation in adolescents are similar to those in adults, and (2) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. Methods IBS patients and controls received subliminal and liminal rectal distension during imaging. Stimulus-induced brain activations were determined. Salience network integrity was evaluated by functional connectivity of its seed regions activated by rectal distension in the insular and cingulate cortices. Key Results Compared with controls, IBS patients demonstrated greater activation to rectal distension in neural structures of the homeostatic afferent and emotional arousal networks, especially the anterior cingulate and insular cortices. Greater brain responses to liminal vs. subliminal distension were observed in both groups. Particularly, IBS is uniquely associated with an excessive coupling of the salience network with the DMN and ECN in their key frontal and parietal node areas. Conclusions & Inferences Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms. PMID:26467966

Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter-speech sound learning in prereaders.

PubMed

Karipidis, Iliana I; Pleisch, Georgette; Brandeis, Daniel; Roth, Alexander; Röthlisberger, Martina; Schneebeli, Maya; Walitza, Susanne; Brem, Silvia

2018-05-08

During reading acquisition, neural reorganization of the human brain facilitates the integration of letters and speech sounds, which enables successful reading. Neuroimaging and behavioural studies have established that impaired audiovisual integration of letters and speech sounds is a core deficit in individuals with developmental dyslexia. This longitudinal study aimed to identify neural and behavioural markers of audiovisual integration that are related to future reading fluency. We simulated the first step of reading acquisition by performing artificial-letter training with prereading children at risk for dyslexia. Multiple logistic regressions revealed that our training provides new precursors of reading fluency at the beginning of reading acquisition. In addition, an event-related potential around 400 ms and functional magnetic resonance imaging activation patterns in the left planum temporale to audiovisual correspondences improved cross-validated prediction of future poor readers. Finally, an exploratory analysis combining simultaneously acquired electroencephalography and hemodynamic data suggested that modulation of temporoparietal brain regions depended on future reading skills. The multimodal approach demonstrates neural adaptations to audiovisual integration in the developing brain that are related to reading outcome. Despite potential limitations arising from the restricted sample size, our results may have promising implications both for identifying poor-reading children and for monitoring early interventions.

A Prototype Symbolic Model of Canonical Functional Neuroanatomy of the Motor System

PubMed Central

Rubin, Daniel L.; Halle, Michael; Musen, Mark; Kikinis, Ron

2008-01-01

Recent advances in bioinformatics have opened entire new avenues for organizing, integrating and retrieving neuroscientific data, in a digital, machine-processable format, which can be at the same time understood by humans, using ontological, symbolic data representations. Declarative information stored in ontological format can be perused and maintained by domain experts, interpreted by machines, and serve as basis for a multitude of decision-support, computerized simulation, data mining, and teaching applications. We have developed a prototype symbolic model of canonical neuroanatomy of the motor system. Our symbolic model is intended to support symbolic lookup, logical inference and mathematical modeling by integrating descriptive, qualitative and quantitative functional neuroanatomical knowledge. Furthermore, we show how our approach can be extended to modeling impaired brain connectivity in disease states, such as common movement disorders. In developing our ontology, we adopted a disciplined modeling approach, relying on a set of declared principles, a high-level schema, Aristotelian definitions, and a frame-based authoring system. These features, along with the use of the Unified Medical Language System (UMLS) vocabulary, enable the alignment of our functional ontology with an existing comprehensive ontology of human anatomy, and thus allow for combining the structural and functional views of neuroanatomy for clinical decision support and neuroanatomy teaching applications. Although the scope of our current prototype ontology is limited to a particular functional system in the brain, it may be possible to adapt this approach for modeling other brain functional systems as well. PMID:18164666

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 a more mature and controlled cognition.

Coherent activity between brain regions that code for value is linked to the malleability of human behavior

PubMed Central

Cooper, Nicole; Bassett, Danielle S.; Falk, Emily B.

2017-01-01

Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave. PMID:28240271

[The search of the "intact" structural and functional brain systems as a paradigm shift in schizophrenia research].

PubMed

Lebedeva, I S

2015-01-01

The search of the structural and functional brain characteristics is one of the most studied directions in the modern biological psychiatry. However, in spite of the numerous studies the results are still controversial. As the necessity of the shift of the current paradigm in schizophrenia research evolves it has been suggested to discriminate not only abnormal but stable functioning neuronal circuits as well. Consequently, the aim is formulated as the search of the minimal brain damage sufficient for disease development. Author analyzed the auditory oddball P300 latency (as a marker of information processing speed), N-acetylaspartate level in the dorsolateral prefrontal cortex (as a marker of neuronal integrity in this brain area) and fractional anisotropy of the fasciculus uncindtus which connects the frontal and temporal lobes (as a marker of white matter bundles microstructure) in 30 patients with schizophrenia and 27 healthy people. The findings showed that all the tested characteristics are not "obligatory" for schizophrenia.

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

PubMed

Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

2017-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease.

INTEGRATIVE ANALYSIS OF GENETIC, GENOMIC AND PHENOTYPIC DATA FOR ETHANOL BEHAVIORS: A NETWORK-BASED PIPELINE FOR IDENTIFYING MECHANISMS AND POTENTIAL DRUG TARGETS

PubMed Central

Bogenpohl, James W.; Mignogna, Kristin M.; Smith, Maren L.; Miles, Michael F.

2016-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce non-biased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease. PMID:27933543

Integrating EEG and fMRI in epilepsy.

PubMed

Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria

2011-02-14

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear interictal spikes. Copyright © 2010 Elsevier Inc. All rights reserved.

Fusing DTI and FMRI Data: A Survey of Methods and Applications

PubMed Central

Zhu, Dajiang; Zhang, Tuo; Jiang, Xi; Hu, Xintao; Chen, Hanbo; Yang, Ning; Lv, Jinglei; Han, Junwei; Guo, Lei; Liu, Tianming

2014-01-01

The relationship between brain structure and function has been one of the centers of research in neuroimaging for decades. In recent years, diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques have been widely available and popular in cognitive and clinical neurosciences for examining the brain’s white matter (WM) micro-structures and gray matter (GM) functions, respectively. Given the intrinsic integration of WM/GM and the complementary information embedded in DTI/fMRI data, it is natural and well-justified to combine these two neuroimaging modalities together to investigate brain structure and function and their relationships simultaneously. In the past decade, there have been remarkable achievements of DTI/fMRI fusion methods and applications in neuroimaging and human brain mapping community. This survey paper aims to review recent advancements on methodologies and applications in incorporating multimodal DTI and fMRI data, and offer our perspectives on future research directions. We envision that effective fusion of DTI/fMRI techniques will play increasingly important roles in neuroimaging and brain sciences in the years to come. PMID:24103849

Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

PubMed Central

Jiang, Xiaoyan; Zhang, Lili; Pu, Hongjian; Hu, Xiaoming; Zhang, Wenting; Cai, Wei; Gao, Yanqin; Leak, Rehana K.; Keep, Richard F.; Bennett, Michael V. L.; Chen, Jun

2017-01-01

The damage borne by the endothelial cells (ECs) forming the blood–brain barrier (BBB) during ischemic stroke and other neurological conditions disrupts the structure and function of the neurovascular unit and contributes to poor patient outcomes. We recently reported that structural aberrations in brain microvascular ECs—namely, uncontrolled actin polymerization and subsequent disassembly of junctional proteins, are a possible cause of the early onset BBB breach that arises within 30–60 min of reperfusion after transient focal ischemia. Here, we investigated the role of heat shock protein 27 (HSP27) as a direct inhibitor of actin polymerization and protectant against BBB disruption after ischemia/reperfusion (I/R). Using in vivo and in vitro models, we found that targeted overexpression of HSP27 specifically within ECs—but not within neurons—ameliorated BBB impairment 1–24 h after I/R. Mechanistically, HSP27 suppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein translocation in brain microvascular ECs, independent of its protective actions against cell death. By preserving BBB integrity after I/R, EC-targeted HSP27 overexpression attenuated the infiltration of potentially destructive neutrophils and macrophages into brain parenchyma, thereby improving long-term stroke outcome. Notably, early poststroke administration of HSP27 attached to a cell-penetrating transduction domain (TAT-HSP27) rapidly elevated HSP27 levels in brain microvessels and ameliorated I/R-induced BBB disruption and subsequent neurological deficits. Thus, the present study demonstrates that HSP27 can function at the EC level to preserve BBB integrity after I/R brain injury. HSP27 may be a therapeutic agent for ischemic stroke and other neurological conditions involving BBB breakdown. PMID:28137866

Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants.

PubMed

El Ters, N M; Vesoulis, Z A; Liao, S M; Smyser, C D; Mathur, A M

2017-08-01

To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF 90 ), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF 90 and bandwidth span (β=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (β=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF 90 , bandwidth span and Burdjalov score remained significant. Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG.

Transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugs.

PubMed

Yee, Benjamin K; Singer, Philipp; Chen, Jiang-Fan; Feldon, Joram; Boison, Detlev

2007-12-01

The neuromodulator adenosine fulfills a unique role in the brain affecting glutamatergic neurotransmission and dopaminergic signaling via activation of adenosine A1 and A2A receptors, respectively. The adenosine system is thus ideally positioned to integrate glutamatergic and dopaminergic neurotransmission, which in turn could affect behavior and cognition. In the adult brain, adenosine levels are largely regulated by its key metabolic enzyme adenosine kinase (ADK), which may assume the role of an 'upstream regulator' of these two neurotransmitter pathways. To test this hypothesis, transgenic mice with an overexpression of ADK in brain (Adk-tg), and therefore reduced brain adenosine levels, were evaluated in a panel of behavioral and psychopharmacological assays to assess possible glutamatergic and dopaminergic dysfunction. In comparison to non-transgenic control mice, Adk-tg mice are characterized by severe learning deficits in the Morris water maze task and in Pavlovian conditioning. The Adk-tg mice also exhibited reduced locomotor reaction to systemic amphetamine, whereas their reaction to the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 was enhanced. Our results confirmed that ADK overexpression could lead to functional concomitant alterations in dopaminergic and glutamatergic functions, which is in keeping with the hypothesized role of ADK in the balance and integration between glutamatergic and dopaminergic neurotransmission. The present findings are of relevance to current pathophysiological hypotheses of schizophrenia and its pharmacotherapy.

C5a alters blood-brain barrier integrity in experimental lupus

PubMed Central

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

2010-01-01

The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6lpr (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL+/+ mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.—Jacob, A., Hack, B., Chiang, E., Garcia, J. G. N., Quigg, R. J., Alexander, J. J. C5a alters blood-brain barrier integrity in experimental lupus. PMID:20065106

Art, energy, and the brain.

PubMed

Pepperell, Robert

2018-01-01

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

Spaceflight Effects on Neurocognitive Performance: Extent, Longevity and Neural Bases

NASA Technical Reports Server (NTRS)

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

Complexity in relational processing predicts changes in functional brain network dynamics.

PubMed

Cocchi, Luca; Halford, Graeme S; Zalesky, Andrew; Harding, Ian H; Ramm, Brentyn J; Cutmore, Tim; Shum, David H K; Mattingley, Jason B

2014-09-01

The ability to link variables is critical to many high-order cognitive functions, including reasoning. It has been proposed that limits in relating variables depend critically on relational complexity, defined formally as the number of variables to be related in solving a problem. In humans, the prefrontal cortex is known to be important for reasoning, but recent studies have suggested that such processes are likely to involve widespread functional brain networks. To test this hypothesis, we used functional magnetic resonance imaging and a classic measure of deductive reasoning to examine changes in brain networks as a function of relational complexity. As expected, behavioral performance declined as the number of variables to be related increased. Likewise, increments in relational complexity were associated with proportional enhancements in brain activity and task-based connectivity within and between 2 cognitive control networks: A cingulo-opercular network for maintaining task set, and a fronto-parietal network for implementing trial-by-trial control. Changes in effective connectivity as a function of increased relational complexity suggested a key role for the left dorsolateral prefrontal cortex in integrating and implementing task set in a trial-by-trial manner. Our findings show that limits in relational processing are manifested in the brain as complexity-dependent modulations of large-scale networks. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SZDB: A Database for Schizophrenia Genetic Research

PubMed Central

Wu, Yong; Yao, Yong-Gang

2017-01-01

Abstract Schizophrenia (SZ) is a debilitating brain disorder with a complex genetic architecture. Genetic studies, especially recent genome-wide association studies (GWAS), have identified multiple variants (loci) conferring risk to SZ. However, how to efficiently extract meaningful biological information from bulk genetic findings of SZ remains a major challenge. There is a pressing need to integrate multiple layers of data from various sources, eg, genetic findings from GWAS, copy number variations (CNVs), association and linkage studies, gene expression, protein–protein interaction (PPI), co-expression, expression quantitative trait loci (eQTL), and Encyclopedia of DNA Elements (ENCODE) data, to provide a comprehensive resource to facilitate the translation of genetic findings into SZ molecular diagnosis and mechanism study. Here we developed the SZDB database (http://www.szdb.org/), a comprehensive resource for SZ research. SZ genetic data, gene expression data, network-based data, brain eQTL data, and SNP function annotation information were systematically extracted, curated and deposited in SZDB. In-depth analyses and systematic integration were performed to identify top prioritized SZ genes and enriched pathways. Multiple types of data from various layers of SZ research were systematically integrated and deposited in SZDB. In-depth data analyses and integration identified top prioritized SZ genes and enriched pathways. We further showed that genes implicated in SZ are highly co-expressed in human brain and proteins encoded by the prioritized SZ risk genes are significantly interacted. The user-friendly SZDB provides high-confidence candidate variants and genes for further functional characterization. More important, SZDB provides convenient online tools for data search and browse, data integration, and customized data analyses. PMID:27451428

Heterogeneous integration of adult-generated granule cells into the epileptic brain

PubMed Central

Murphy, Brian L.; Pun, Raymund Y.K.; Yin, Hulian; Faulkner, Christian R.; Loepke, Andreas W.; Danzer, Steve C.

2011-01-01

The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles, while others contribute to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice. The majority of newborn cells exposed to an epileptogenic insult exhibited reductions in dendritic spine number, suggesting reduced excitatory input to these cells. A significant subset, however, exhibited higher spine numbers. These latter cells tended to have enlarged cell bodies, long basal dendrites or both. Moreover, cells with basal dendrites received significantly more recurrent mossy fiber input through their apical dendrites, indicating that these cells are robustly integrated into the pathological circuitry of the epileptic brain. These data imply that newborn cells play complex – and potentially conflicting – roles in epilepsy. PMID:21209195

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

PubMed

Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J

2017-04-08

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Words are not enough: nonword repetition as an indicator of arcuate fasciculus integrity during brain tumor resection.

PubMed

Sierpowska, Joanna; Gabarrós, Andreu; Fernandez-Coello, Alejandro; Camins, Àngels; Castañer, Sara; Juncadella, Montserrat; Morís, Joaquín; Rodríguez-Fornells, Antoni

2017-02-01

OBJECTIVE Subcortical electrical stimulation during brain surgery may allow localization of functionally crucial white matter fibers and thus tailoring of the tumor resection according to its functional limits. The arcuate fasciculus (AF) is a white matter bundle connecting frontal, temporal, and parietal cortical areas that is often disrupted by left brain lesions. It plays a critical role in several cognitive functions related to phonological processing, but current intraoperative monitoring methods do not yet allow mapping of this tract with sufficient precision. In the present study the authors aimed to test a new paradigm for the intraoperative monitoring of the AF. METHODS In this report, the authors studied 12 patients undergoing awake brain surgery for tumor resection with a related risk of AF damage. To preserve AF integrity and the cognitive processes sustained by this tract in the intraoperative context, the authors used real word repetition (WR) and nonword repetition (NWR) tasks as complements to standard picture naming. RESULTS Compared with the errors identified by WR or picture naming, the NWR task allowed the detection of subtle errors possibly related to AF alterations. Moreover, only 3 patients demonstrated phonological paraphasias in standard picture naming, and in 2 of these patients the paraphasias co-occurred with the total loss of WR and NWR ability. Before surgery, lesion volume predicted a patient's NWR performance. CONCLUSIONS The authors suggest that monitoring NWR intraoperatively may complement the standard naming tasks and could permit better preservation of the important language production functions subserved by the AF.

Large-Scale Functional Brain Network Reorganization During Taoist Meditation.

PubMed

Jao, Tun; Li, Chia-Wei; Vértes, Petra E; Wu, Changwei Wesley; Achard, Sophie; Hsieh, Chao-Hsien; Liou, Chien-Hui; Chen, Jyh-Horng; Bullmore, Edward T

2016-02-01

Meditation induces a distinct and reversible mental state that provides insights into brain correlates of consciousness. We explored brain network changes related to meditation by graph theoretical analysis of resting-state functional magnetic resonance imaging data. Eighteen Taoist meditators with varying levels of expertise were scanned using a within-subjects counterbalanced design during resting and meditation states. State-related differences in network topology were measured globally and at the level of individual nodes and edges. Although measures of global network topology, such as small-worldness, were unchanged, meditation was characterized by an extensive and expertise-dependent reorganization of the hubs (highly connected nodes) and edges (functional connections). Areas of sensory cortex, especially the bilateral primary visual and auditory cortices, and the bilateral temporopolar areas, which had the highest degree (or connectivity) during the resting state, showed the biggest decrease during meditation. Conversely, bilateral thalamus and components of the default mode network, mainly the bilateral precuneus and posterior cingulate cortex, had low degree in the resting state but increased degree during meditation. Additionally, these changes in nodal degree were accompanied by reorganization of anatomical orientation of the edges. During meditation, long-distance longitudinal (antero-posterior) edges increased proportionally, whereas orthogonal long-distance transverse (right-left) edges connecting bilaterally homologous cortices decreased. Our findings suggest that transient changes in consciousness associated with meditation introduce convergent changes in the topological and spatial properties of brain functional networks, and the anatomical pattern of integration might be as important as the global level of integration when considering the network basis for human consciousness.

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: The Effects of Exercise Interventions

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Erdeniz. B.; Kofman, I. S.; DeDios, Y. E.; Szecsy, D. L.; Riascos-Castaneda, R. F.; Wood, S. J.; Bloomberg, J. J.

2014-01-01

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. Our ongoing bed rest participants are also engaging in exercise studies directed by Dr. Lori Ploutz Snyder. In this presentation, I will briefly highlight the existing literature linking exercise and fitness to brain and behavioral functions. I will also overview the metrics from my study that could be investigated in relation to the exercise and control subgroups.

Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy

PubMed Central

Bonilha, Leonardo; Tabesh, Ali; Dabbs, Kevin; Hsu, David A.; Stafstrom, Carl E.; Hermann, Bruce P.; Lin, Jack J.

2014-01-01

Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large-scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early-life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new-onset seizures and 28 healthy controls. Children with new-onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared to controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large-scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment. PMID:24453089

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

PubMed

Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

2017-09-01

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional near-infrared spectroscopy (fNIRS) brain imaging of multi-sensory integration during computerized dynamic posturography in middle-aged and older adults.

PubMed

Lin, Chia-Cheng; Barker, Jeffrey W; Sparto, Patrick J; Furman, Joseph M; Huppert, Theodore J

2017-04-01

Studies suggest that aging affects the sensory re-weighting process, but the neuroimaging evidence is minimal. Functional Near-Infrared Spectroscopy (fNIRS) is a novel neuroimaging tool that can detect brain activities during dynamic movement condition. In this study, fNIRS was used to investigate the hemodynamic changes in the frontal-lateral, temporal-parietal, and occipital regions of interest (ROIs) during four sensory integration conditions that manipulated visual and somatosensory feedback in 15 middle-aged and 15 older adults. The results showed that the temporal-parietal ROI was activated more when somatosensory and visual information were absent in both groups, which indicated the sole use of vestibular input for maintaining balance. While both older adults and middle-aged adults had greater activity in most brain ROIs during changes in the sensory conditions, the older adults had greater increases in the occipital ROI and frontal-lateral ROIs. These findings suggest a cortical component to sensory re-weighting that is more distributed and requires greater attention in older adults.

Left Inferior Frontal Cortex and Syntax: Function, Structure and Behaviour in Patients with Left Hemisphere Damage

ERIC Educational Resources Information Center

Tyler, Lorraine K.; Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left…

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

PubMed

Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

An Anatomically Constrained Model for Path Integration in the Bee Brain.

PubMed

Stone, Thomas; Webb, Barbara; Adden, Andrea; Weddig, Nicolai Ben; Honkanen, Anna; Templin, Rachel; Wcislo, William; Scimeca, Luca; Warrant, Eric; Heinze, Stanley

2017-10-23

Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic-flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term cilostazol administration ameliorates memory decline in senescence-accelerated mouse prone 8 (SAMP8) through a dual effect on cAMP and blood-brain barrier.

PubMed

Yanai, Shuichi; Toyohara, Jun; Ishiwata, Kiichi; Ito, Hideki; Endo, Shogo

2017-04-01

Phosphodiesterases (PDEs), which hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2- 18 F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

NASA Astrophysics Data System (ADS)

Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

2015-03-01

Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

Consciousness, cognition and brain networks: New perspectives.

PubMed

Aldana, E M; Valverde, J L; Fábregas, N

2016-10-01

A detailed analysis of the literature on consciousness and cognition mechanisms based on the neural networks theory is presented. The immune and inflammatory response to the anesthetic-surgical procedure induces modulation of neuronal plasticity by influencing higher cognitive functions. Anesthetic drugs can cause unconsciousness, producing a functional disruption of cortical and thalamic cortical integration complex. The external and internal perceptions are processed through an intricate network of neural connections, involving the higher nervous activity centers, especially the cerebral cortex. This requires an integrated model, formed by neural networks and their interactions with highly specialized regions, through large-scale networks, which are distributed throughout the brain collecting information flow of these perceptions. Functional and effective connectivity between large-scale networks, are essential for consciousness, unconsciousness and cognition. It is what is called the "human connectome" or map neural networks. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Global integration of the hot-state brain network of appetite predicts short term weight loss in older adult.

PubMed

Paolini, Brielle M; Laurienti, Paul J; Simpson, Sean L; Burdette, Jonathan H; Lyday, Robert G; Rejeski, W Jack

2015-01-01

Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL) remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A) predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE). The present work is a sub-study (n = 56) of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI) scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC), superior temporal pole (STP), amygdala and the parahippocampal gyrus) were highly integrated as evidenced by the results of a principal component analysis (PCA). After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy) and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of WL.

Your perspective and my benefit: multiple lesion models of self-other integration strategies during social bargaining.

PubMed

Melloni, Margherita; Billeke, Pablo; Baez, Sandra; Hesse, Eugenia; de la Fuente, Laura; Forno, Gonzalo; Birba, Agustina; García-Cordero, Indira; Serrano, Cecilia; Plastino, Angelo; Slachevsky, Andrea; Huepe, David; Sigman, Mariano; Manes, Facundo; García, Adolfo M; Sedeño, Lucas; Ibáñez, Agustín

2016-11-01

Recursive social decision-making requires the use of flexible, context-sensitive long-term strategies for negotiation. To succeed in social bargaining, participants' own perspectives must be dynamically integrated with those of interactors to maximize self-benefits and adapt to the other's preferences, respectively. This is a prerequisite to develop a successful long-term self-other integration strategy. While such form of strategic interaction is critical to social decision-making, little is known about its neurocognitive correlates. To bridge this gap, we analysed social bargaining behaviour in relation to its structural neural correlates, ongoing brain dynamics (oscillations and related source space), and functional connectivity signatures in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal stroke: behavioural variant frontotemporal dementia, Alzheimer's disease, and frontal lesions. All groups showed preserved basic bargaining indexes. However, impaired self-other integration strategy was found in patients with behavioural variant frontotemporal dementia and frontal lesions, suggesting that social bargaining critically depends on the integrity of prefrontal regions. Also, associations between behavioural performance and data from voxel-based morphometry and voxel-based lesion-symptom mapping revealed a critical role of prefrontal regions in value integration and strategic decisions for self-other integration strategy. Furthermore, as shown by measures of brain dynamics and related sources during the task, the self-other integration strategy was predicted by brain anticipatory activity (alpha/beta oscillations with sources in frontotemporal regions) associated with expectations about others' decisions. This pattern was reduced in all clinical groups, with greater impairments in behavioural variant frontotemporal dementia and frontal lesions than Alzheimer's disease. Finally, connectivity analysis from functional magnetic resonance imaging evidenced a fronto-temporo-parietal network involved in successful self-other integration strategy, with selective compromise of long-distance connections in frontal disorders. In sum, this work provides unprecedented evidence of convergent behavioural and neurocognitive signatures of strategic social bargaining in different lesion models. Our findings offer new insights into the critical roles of prefrontal hubs and associated temporo-parietal networks for strategic social negotiation. © 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.

Relationships among cognition, emotion, and motivation: implications for intervention and neuroplasticity in psychopathology

PubMed Central

Crocker, Laura D.; Heller, Wendy; Warren, Stacie L.; O'Hare, Aminda J.; Infantolino, Zachary P.; Miller, Gregory A.

2013-01-01

Emotion-cognition and motivation-cognition relationships and related brain mechanisms are receiving increasing attention in the clinical research literature as a means of understanding diverse types of psychopathology and improving biological and psychological treatments. This paper reviews and integrates some of the growing evidence for cognitive biases and deficits in depression and anxiety, how these disruptions interact with emotional and motivational processes, and what brain mechanisms appear to be involved. This integration sets the stage for understanding the role of neuroplasticity in implementing change in cognitive, emotional, and motivational processes in psychopathology as a function of intervention. PMID:23781184

Integrated semiconductor optical sensors for chronic, minimally-invasive imaging of brain function.

PubMed

Lee, Thomas T; Levi, Ofer; Cang, Jianhua; Kaneko, Megumi; Stryker, Michael P; Smith, Stephen J; Shenoy, Krishna V; Harris, James S

2006-01-01

Intrinsic optical signal (IOS) imaging is a widely accepted technique for imaging brain activity. We propose an integrated device consisting of interleaved arrays of gallium arsenide (GaAs) based semiconductor light sources and detectors operating at telecommunications wavelengths in the near-infrared. Such a device will allow for long-term, minimally invasive monitoring of neural activity in freely behaving subjects, and will enable the use of structured illumination patterns to improve system performance. In this work we describe the proposed system and show that near-infrared IOS imaging at wavelengths compatible with semiconductor devices can produce physiologically significant images in mice, even through skull.

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

PubMed Central

O’Reilly, Jill X.; Croxson, Paula L.; Jbabdi, Saad; Sallet, Jerome; Noonan, MaryAnn P.; Mars, Rogier B.; Browning, Philip G.F.; Wilson, Charles R. E.; Mitchell, Anna S.; Miller, Karla L.; Rushworth, Matthew F. S.; Baxter, Mark G.

2013-01-01

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states. PMID:23924609

Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

PubMed

Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

2016-04-01

Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © 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.

State-dependencies of learning across brain scales

PubMed Central

Ritter, Petra; Born, Jan; Brecht, Michael; Dinse, Hubert R.; Heinemann, Uwe; Pleger, Burkhard; Schmitz, Dietmar; Schreiber, Susanne; Villringer, Arno; Kempter, Richard

2015-01-01

Learning is a complex brain function operating on different time scales, from milliseconds to years, which induces enduring changes in brain dynamics. The brain also undergoes continuous “spontaneous” shifts in states, which, amongst others, are characterized by rhythmic activity of various frequencies. Besides the most obvious distinct modes of waking and sleep, wake-associated brain states comprise modulations of vigilance and attention. Recent findings show that certain brain states, particularly during sleep, are essential for learning and memory consolidation. Oscillatory activity plays a crucial role on several spatial scales, for example in plasticity at a synaptic level or in communication across brain areas. However, the underlying mechanisms and computational rules linking brain states and rhythms to learning, though relevant for our understanding of brain function and therapeutic approaches in brain disease, have not yet been elucidated. Here we review known mechanisms of how brain states mediate and modulate learning by their characteristic rhythmic signatures. To understand the critical interplay between brain states, brain rhythms, and learning processes, a wide range of experimental and theoretical work in animal models and human subjects from the single synapse to the large-scale cortical level needs to be integrated. By discussing results from experiments and theoretical approaches, we illuminate new avenues for utilizing neuronal learning mechanisms in developing tools and therapies, e.g., for stroke patients and to devise memory enhancement strategies for the elderly. PMID:25767445

C5a alters blood-brain barrier integrity in experimental lupus.

PubMed

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

2010-06-01

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

The Functional Neuroanatomy of Prelexical Processing in Speech Perception

ERIC Educational Resources Information Center

Scott, Sophie K.; Wise, Richard J. S.

2004-01-01

In this paper we attempt to relate the prelexical processing of speech, with particular emphasis on functional neuroimaging studies, to the study of auditory perceptual systems by disciplines in the speech and hearing sciences. The elaboration of the sound-to-meaning pathways in the human brain enables their integration into models of the human…

Sensori-Motor Experience Leads to Changes in Visual Processing in the Developing Brain

ERIC Educational Resources Information Center

James, Karin Harman

2010-01-01

Since Broca's studies on language processing, cortical functional specialization has been considered to be integral to efficient neural processing. A fundamental question in cognitive neuroscience concerns the type of learning that is required for functional specialization to develop. To address this issue with respect to the development of neural…

Learning-dependent plasticity with and without training in the human brain.

PubMed

Zhang, Jiaxiang; Kourtzi, Zoe

2010-07-27

Long-term experience through development and evolution and shorter-term training in adulthood have both been suggested to contribute to the optimization of visual functions that mediate our ability to interpret complex scenes. However, the brain plasticity mechanisms that mediate the detection of objects in cluttered scenes remain largely unknown. Here, we combine behavioral and functional MRI (fMRI) measurements to investigate the human-brain mechanisms that mediate our ability to learn statistical regularities and detect targets in clutter. We show two different routes to visual learning in clutter with discrete brain plasticity signatures. Specifically, opportunistic learning of regularities typical in natural contours (i.e., collinearity) can occur simply through frequent exposure, generalize across untrained stimulus features, and shape processing in occipitotemporal regions implicated in the representation of global forms. In contrast, learning to integrate discontinuities (i.e., elements orthogonal to contour paths) requires task-specific training (bootstrap-based learning), is stimulus-dependent, and enhances processing in intraparietal regions implicated in attention-gated learning. We propose that long-term experience with statistical regularities may facilitate opportunistic learning of collinear contours, whereas learning to integrate discontinuities entails bootstrap-based training for the detection of contours in clutter. These findings provide insights in understanding how long-term experience and short-term training interact to shape the optimization of visual recognition processes.

New experimental models of the blood-brain barrier for CNS drug discovery

PubMed Central

Kaisar, Mohammad A.; Sajja, Ravi K.; Prasad, Shikha; Abhyankar, Vinay V.; Liles, Taylor; Cucullo, Luca

2017-01-01

Introduction The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies. Additionally, the authors laid out a roadmap for the integration of microfluidics and stem cell biology as a holistic approach for the development of novel in vitro BBB platforms. Expert opinion Development of effective CNS drugs has been hindered by the lack of reliable strategies to mimic the BBB and cerebrovascular impairments in vitro. Technological advancements in BBB modeling have fostered the development of highly integrative and quasi- physiological in vitro platforms to support the process of drug discovery. These advanced in vitro tools are likely to further current understanding of the cerebrovascular modulatory mechanisms. PMID:27782770

Mental retardation-related protease, motopsin (prss12), binds to the BRICHOS domain of the integral membrane protein 2a.

PubMed

Mitsui, Shinichi; Osako, Yoji; Yuri, Kazunari

2014-01-01

Motopsin (prss12), a mosaic serine protease secreted by neuronal cells, is believed to be important for cognitive function, as the loss of its function causes severe nonsyndromic mental retardation. To understand the molecular role of motopsin, we identified the integral membrane protein 2a (Itm2a) as a motopsin-interacting protein using a yeast two-hybrid system. A pull-down assay showed that the BRICHOS domain of Itm2a was essential for this interaction. Motopsin and Itm2a co-localized in COS cells and in cultured neurons when transiently expressed in these cells. Both proteins were co-immunoprecipitated from lysates of these transfected COS cells. Itm2a was strongly detected in a brain lysate prepared between postnatal day 0 and 10, during which period motopsin protein was also enriched in the brain. Immunohistochemistry detected Itm2a as patchy spots along endothelial cells of brain capillaries (which also expressed myosin II regulatory light chain [RLC]), and on glial fibrillary acidic protein (GFAP)-positive processes in the developing cerebral cortex. The data raise the possibility that secreted motopsin interacts with endothelial cells in the developing brain. © 2013 International Federation for Cell Biology.

An alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer's disease and neurodegeneration.

PubMed

Pike, Adrianne F; Kramer, Nynke I; Blaauboer, Bas J; Seinen, Willem; Brands, Ruud

2015-01-25

Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neural network configuration and efficiency underlies individual differences in spatial orientation ability.

PubMed

Arnold, Aiden E G F; Protzner, Andrea B; Bray, Signe; Levy, Richard M; Iaria, Giuseppe

2014-02-01

Spatial orientation is a complex cognitive process requiring the integration of information processed in a distributed system of brain regions. Current models on the neural basis of spatial orientation are based primarily on the functional role of single brain regions, with limited understanding of how interaction among these brain regions relates to behavior. In this study, we investigated two sources of variability in the neural networks that support spatial orientation--network configuration and efficiency--and assessed whether variability in these topological properties relates to individual differences in orientation accuracy. Participants with higher accuracy were shown to express greater activity in the right supramarginal gyrus, the right precentral cortex, and the left hippocampus, over and above a core network engaged by the whole group. Additionally, high-performing individuals had increased levels of global efficiency within a resting-state network composed of brain regions engaged during orientation and increased levels of node centrality in the right supramarginal gyrus, the right primary motor cortex, and the left hippocampus. These results indicate that individual differences in the configuration of task-related networks and their efficiency measured at rest relate to the ability to spatially orient. Our findings advance systems neuroscience models of orientation and navigation by providing insight into the role of functional integration in shaping orientation behavior.

Psychophysiological correlates of aggression and violence: an integrative review.

PubMed

Patrick, Christopher J

2008-08-12

This paper reviews existing psychophysiological studies of aggression and violent behaviour including research employing autonomic, electrocortical and neuroimaging measures. Robust physiological correlates of persistent aggressive behaviour evident in this literature include low baseline heart rate, enhanced autonomic reactivity to stressful or aversive stimuli, enhanced EEG slow wave activity, reduced P300 brain potential response and indications from structural and functional neuroimaging studies of dysfunction in frontocortical and limbic brain regions that mediate emotional processing and regulation. The findings are interpreted within a conceptual framework that draws on two integrative models in the literature. The first is a recently developed hierarchical model of impulse control (externalizing) problems, in which various disinhibitory syndromes including aggressive and addictive behaviours of different kinds are seen as arising from common as well as distinctive aetiologic factors. This model represents an approach to organizing these various interrelated phenotypes and investigating their common and distinctive aetiologic substrates. The other is a neurobiological model that posits impairments in affective regulatory circuits in the brain as a key mechanism for impulsive aggressive behaviour. This model provides a perspective for integrating findings from studies employing different measures that have implicated varying brain structures and physiological systems in violent and aggressive behaviour.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Brain network of semantic integration in sentence reading: insights from independent component analysis and graph theoretical analysis.

PubMed

Ye, Zheng; Doñamayor, Nuria; Münte, Thomas F

2014-02-01

A set of cortical and sub-cortical brain structures has been linked with sentence-level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required participants to silently read sentences with semantically congruent or incongruent endings and analyzed the network properties of the brain with two approaches, independent component analysis (ICA) and graph theoretical analysis (GTA). The GTA suggested that the whole-brain network is topologically stable across conditions. The ICA revealed a network comprising the supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the incongruity of sentence ending. Furthermore, the GTA specified that the connections between the left SMA and left caudate nucleus as well as that between the left caudate nucleus and right thalamus were stronger in response to incongruent vs. congruent endings. Copyright © 2012 Wiley Periodicals, Inc.

Reliability of Visual and Somatosensory Feedback in Skilled Movement: The Role of the Cerebellum.

PubMed

Mizelle, J C; Oparah, Alexis; Wheaton, Lewis A

2016-01-01

The integration of vision and somatosensation is required to allow for accurate motor behavior. While both sensory systems contribute to an understanding of the state of the body through continuous updating and estimation, how the brain processes unreliable sensory information remains to be fully understood in the context of complex action. Using functional brain imaging, we sought to understand the role of the cerebellum in weighting visual and somatosensory feedback by selectively reducing the reliability of each sense individually during a tool use task. We broadly hypothesized upregulated activation of the sensorimotor and cerebellar areas during movement with reduced visual reliability, and upregulated activation of occipital brain areas during movement with reduced somatosensory reliability. As specifically compared to reduced somatosensory reliability, we expected greater activations of ipsilateral sensorimotor cerebellum for intact visual and somatosensory reliability. Further, we expected that ipsilateral posterior cognitive cerebellum would be affected with reduced visual reliability. We observed that reduced visual reliability results in a trend towards the relative consolidation of sensorimotor activation and an expansion of cerebellar activation. In contrast, reduced somatosensory reliability was characterized by the absence of cerebellar activations and a trend towards the increase of right frontal, left parietofrontal activation, and temporo-occipital areas. Our findings highlight the role of the cerebellum for specific aspects of skillful motor performance. This has relevance to understanding basic aspects of brain functions underlying sensorimotor integration, and provides a greater understanding of cerebellar function in tool use motor control.

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession

PubMed Central

Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M.; Mattson, Mark P.

2012-01-01

Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathological accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated Tau (p-Tau) in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the NAD+ precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. NAD+ biosynthesis, autophagy and PI3K signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and p-Tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (Akt and ERKs) and the transcription factor cyclic AMP response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system. PMID:23273573

Direct and efficient transfection of mouse neural stem cells and mature neurons by in vivo mRNA electroporation.

PubMed

Bugeon, Stéphane; de Chevigny, Antoine; Boutin, Camille; Coré, Nathalie; Wild, Stefan; Bosio, Andreas; Cremer, Harold; Beclin, Christophe

2017-11-01

In vivo brain electroporation of DNA expression vectors is a widely used method for lineage and gene function studies in the developing and postnatal brain. However, transfection efficiency of DNA is limited and adult brain tissue is refractory to electroporation. Here, we present a systematic study of mRNA as a vector for acute genetic manipulation in the developing and adult brain. We demonstrate that mRNA electroporation is far more efficient than DNA electroporation, and leads to faster and more homogeneous protein expression in vivo Importantly, mRNA electroporation allows the manipulation of neural stem cells and postmitotic neurons in the adult brain using minimally invasive procedures. Finally, we show that this approach can be efficiently used for functional studies, as exemplified by transient overexpression of the neurogenic factor Myt1l and by stably inactivating Dicer nuclease in vivo in adult born olfactory bulb interneurons and in fully integrated cortical projection neurons. © 2017. Published by The Company of Biologists Ltd.

Bayesian estimation inherent in a Mexican-hat-type neural network

NASA Astrophysics Data System (ADS)

Takiyama, Ken

2016-05-01

Brain functions, such as perception, motor control and learning, and decision making, have been explained based on a Bayesian framework, i.e., to decrease the effects of noise inherent in the human nervous system or external environment, our brain integrates sensory and a priori information in a Bayesian optimal manner. However, it remains unclear how Bayesian computations are implemented in the brain. Herein, I address this issue by analyzing a Mexican-hat-type neural network, which was used as a model of the visual cortex, motor cortex, and prefrontal cortex. I analytically demonstrate that the dynamics of an order parameter in the model corresponds exactly to a variational inference of a linear Gaussian state-space model, a Bayesian estimation, when the strength of recurrent synaptic connectivity is appropriately stronger than that of an external stimulus, a plausible condition in the brain. This exact correspondence can reveal the relationship between the parameters in the Bayesian estimation and those in the neural network, providing insight for understanding brain functions.

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Correlation between standardized assessment of concussion scores and small-world brain network in mild traumatic brain injury.

PubMed

Yan, Yan; Song, Jian; Xu, Guozheng; Yao, Shun; Cao, Chenglong; Li, Chang; Peng, Guibao; Du, Hao

2017-10-01

This study investigated the characteristics of the small-world brain network architecture of patients with mild traumatic brain injury (MTBI), and a correlation between brain functional connectivity network properties in the resting-state fMRI and Standardized Assessment of Concussion (SAC) parameters. The neurological conditions of 22 MTBI patients and 17 normal control individuals were evaluated according to the SAC. Resting-state fMRI was performed in all subjects 3 and 7days after injury respectively. After preprocessing the fMRI data, cortex functional regions were marked using AAL90 and Dosenbach160 templates. The small-world network parameters and areas under the integral curves were computed in the range of sparsity from 0.01 to 0.5. Independent-sample t-tests were used to compare these parameters between the MTBI and control group. Significantly different parameters were investigated for correlations with SAC scores; those that correlated were chosen for further curve fitting. The clustering coefficient, the communication efficiency across in local networks, and the strength of connectivity were all higher in MTBI patients relative to control individuals. Parameters in 160 brain regions of the MTBI group significantly correlated with total SAC score and score for attention; the network parameters may be a quadratic function of attention scores of SAC and a cubic function of SAC scores. MTBI patients were characterized by elevated communication efficiency across global brain regions, and in local networks, and strength of mean connectivity. These features may be associated with brain function compensation. The network parameters significantly correlated with SAC total and attention scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effects of Spaceflight and a Spaceflight Analog on Neurocognitive Perfonnance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Erdeniz, B.; Kofman, I. S.; DeDios, Y. E.; Szecsy, D. L.; Riascos-Castaneda, R. F.; Wood, S. J.; Bloomberg, J. J.

2014-01-01

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. With the bedrest study, we will be able to determine the neural and neurocognitive effects of extended duration unloading, reduced sensory inputs, and increased cephalic fluid distribution. This will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe in the flight study. In this presentation I will discuss preliminary results from six participants who have undergone the bed rest protocol. These individuals show decrements in balance and functional mobility, and alterations in brain structure and function, in association with extended bed rest.

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

PubMed Central

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

2012-01-01

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

Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

PubMed

Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

2016-09-01

Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

PubMed

Colton, Carol A

2013-03-01

Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.

Brain systems underlying susceptibility to helplessness and depression.

PubMed

Shumake, J; Gonzalez-Lima, F

2003-09-01

There has been a relative lack of research into the neurobiological predispositions that confer vulnerability to depression. This article reviews functional brain mappings from a genetic animal model, the congenitally helpless rat, which is predisposed to develop learned helplessness. Neurometabolic findings from this model are integrated with the neuroscientific literature from other animal models of depression as well as depressed humans. Changes in four major brain systems are suggested to underlie susceptibility to helplessness and possibly depression: (a) an unbalanced prefrontal-cingulate cortical system, (b) a dissociated hypothalamic-pituitary-adrenal axis, (c) a dissociated septal-hippocampal system, and (d) a hypoactive brain reward system, as exemplified by a hypermetabolic habenula-interpeduncular nucleus pathway and a hypometabolic ventral tegmental area-striatum pathway. Functional interconnections and causal relationships among these systems are considered and further experiments are suggested, with theoretical attention to how an abnormality in any one system could affect the others.

Testosterone affects language areas of the adult human brain.

PubMed

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

2016-05-01

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

Neuronal integration of dynamic sources: Bayesian learning and Bayesian inference.

PubMed

Siegelmann, Hava T; Holzman, Lars E

2010-09-01

One of the brain's most basic functions is integrating sensory data from diverse sources. This ability causes us to question whether the neural system is computationally capable of intelligently integrating data, not only when sources have known, fixed relative dependencies but also when it must determine such relative weightings based on dynamic conditions, and then use these learned weightings to accurately infer information about the world. We suggest that the brain is, in fact, fully capable of computing this parallel task in a single network and describe a neural inspired circuit with this property. Our implementation suggests the possibility that evidence learning requires a more complex organization of the network than was previously assumed, where neurons have different specialties, whose emergence brings the desired adaptivity seen in human online inference.

Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis.

PubMed

Valero, Jorge; Paris, Iñaki; Sierra, Amanda

2016-04-20

Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

[Sleep-wake cycle and memory consolidation].

PubMed

Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

2007-01-01

Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

Finer parcellation reveals detailed correlational structure of resting-state fMRI signals.

PubMed

Dornas, João V; Braun, Jochen

2018-01-15

Even in resting state, the human brain generates functional signals (fMRI) with complex correlational structure. To simplify this structure, it is common to parcellate a standard brain into coarse chunks. Finer parcellations are considered less reproducible and informative, due to anatomical and functional variability of individual brains. Grouping signals with similar local correlation profiles, restricted to each anatomical region (Tzourio-Mazoyer et al., 2002), we divide a standard brain into 758 'functional clusters' averaging 1.7cm 3 gray matter volume ('MD758' parcellation). We compare 758 'spatial clusters' of similar size ('S758'). 'Functional clusters' are spatially contiguous and cluster quality (integration and segregation of temporal variance) is far superior to 'spatial clusters', comparable to multi-modal parcellations of half the resolution (Craddock et al., 2012; Glasser et al., 2016). Moreover, 'functional clusters' capture many long-range functional correlations, with O(10 5 ) reproducibly correlated cluster pairs in different anatomical regions. The pattern of functional correlations closely mirrors long-range anatomical connectivity established by fibre tracking. MD758 is comparable to coarser parcellations (Craddock et al., 2012; Glasser et al., 2016) in terms of cluster quality, correlational structure (54% relative mutual entropy vs 60% and 61%), and sparseness (35% significant pairwise correlations vs 36% and 44%). We describe and evaluate a simple path to finer functional parcellations of the human brain. Detailed correlational structure is surprisingly consistent between individuals, opening new possibilities for comparing functional correlations between cognitive conditions, states of health, or pharmacological interventions. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Zinc Signal in Brain Diseases.

PubMed

Portbury, Stuart D; Adlard, Paul A

2017-11-23

The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer's disease or negative outcomes following brain injury.

Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

PubMed Central

Garza-Lombó, Carla; Gonsebatt, María E.

2016-01-01

The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

Neurocognitive enhancement in older adults: comparison of three cognitive training tasks to test a hypothesis of training transfer in brain connectivity.

PubMed

Strenziok, Maren; Parasuraman, Raja; Clarke, Ellen; Cisler, Dean S; Thompson, James C; Greenwood, Pamela M

2014-01-15

The ultimate goal of cognitive enhancement as an intervention for age-related cognitive decline is transfer to everyday cognitive functioning. Development of training methods that transfer broadly to untrained cognitive tasks (far transfer) requires understanding of the neural bases of training and far transfer effects. We used cognitive training to test the hypothesis that far transfer is associated with altered attentional control demands mediated by the dorsal attention network and trained sensory cortex. In an exploratory study, we randomly assigned 42 healthy older adults to six weeks of training on Brain Fitness (BF-auditory perception), Space Fortress (SF-visuomotor/working memory), or Rise of Nations (RON-strategic reasoning). Before and after training, cognitive performance, diffusion-derived white matter integrity, and functional connectivity of the superior parietal cortex (SPC) were assessed. We found the strongest effects from BF training, which transferred to everyday problem solving and reasoning and selectively changed integrity of occipito-temporal white matter associated with improvement on untrained everyday problem solving. These results show that cognitive gain from auditory perception training depends on heightened white matter integrity in the ventral attention network. In BF and SF (which also transferred positively), a decrease in functional connectivity between SPC and inferior temporal lobe (ITL) was observed compared to RON-which did not transfer to untrained cognitive function. These findings highlight the importance for cognitive training of top-down control of sensory processing by the dorsal attention network. Altered brain connectivity - observed in the two training tasks that showed far transfer effects - may be a marker for training success. © 2013 Elsevier Inc. All rights reserved.

Superior temporal sulcus--It's my area: or is it?

PubMed

Hein, Grit; Knight, Robert T

2008-12-01

The superior temporal sulcus (STS) is the chameleon of the human brain. Several research areas claim the STS as the host brain region for their particular behavior of interest. Some see it as one of the core structures for theory of mind. For others, it is the main region for audiovisual integration. It plays an important role in biological motion perception, but is also claimed to be essential for speech processing and processing of faces. We review the foci of activations in the STS from multiple functional magnetic resonance imaging studies, focusing on theory of mind, audiovisual integration, motion processing, speech processing, and face processing. The results indicate a differentiation of the STS region in an anterior portion, mainly involved in speech processing, and a posterior portion recruited by cognitive demands of all these different research areas. The latter finding argues against a strict functional subdivision of the STS. In line with anatomical evidence from tracer studies, we propose that the function of the STS varies depending on the nature of network coactivations with different regions in the frontal cortex and medial-temporal lobe. This view is more in keeping with the notion that the same brain region can support different cognitive operations depending on task-dependent network connections, emphasizing the role of network connectivity analysis in neuroimaging.

We should be using nonlinear indices when relating heart-rate dynamics to cognition and mood

PubMed Central

Young, Hayley; Benton, David

2015-01-01

Both heart rate (HR) and brain functioning involve the integrated output of a multitude of regulatory mechanisms, that are not quantified adequately by linear approximations such as means and standard deviations. It was therefore considered whether non-linear measures of HR complexity are more strongly associated with cognition and mood. Whilst resting, the inter-beat (R-R) time series of twenty-one males and twenty-four females were measured for five minutes. The data were summarised using time, frequency and nonlinear complexity measures. Attention, memory, reaction times, mood and cortisol levels were assessed. Nonlinear HR indices captured additional information, enabling a greater percentage of the variance in behaviour to be explained. On occasions non-linear indices were related to aspects for behaviour, for example focused attention and cortisol production, when time or frequency indices were not. These effects were sexually dimorphic with HR complexity being more strongly associated with the behaviour of females. It was concluded that nonlinear rather than linear methods of summarizing the HR times series offers a novel way of relating brain functioning and behaviour. It should be considered whether non-linear measures of HR complexity can be used as a biomarker of the integrated functioning of the brain. PMID:26565560

Challenges and Opportunities in Mining Neuroscience Data

PubMed Central

Akil, Huda; Martone, Maryann E.; Van Essen, David C.

2011-01-01

Understanding the brain requires a broad range of approaches and methods from the domains of biology, psychology, chemistry, physics, and mathematics. The fundamental challenge is to decipher the “neural choreography” associated with complex behaviors and functions, including thoughts, memories, actions, and emotions. This demands the acquisition and integration of vast amounts of data of many types, at multiple scales in time and in space. Here, we discuss the need for neuroinformatics approaches to accelerate progress, using several illustrative examples. The nascent field of ‘connectomics’ aims to comprehensively describe neuronal connectivity at either a macroscopic level (long-distance pathways for the entire brain) or a microscopic level (axons, dendrites, synapses in a small brain region). The Neuroscience Information Framework encompasses all of neuroscience and facilitates integration of existing knowledge and databases of many types. These examples illustrate the opportunities and challenges of data mining across multiple tiers of neuroscience information and underscore the need for cultural and infrastructure changes if neuroinformatics is to fulfill its potential to advance our understanding of the brain. PMID:21311009

Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

PubMed Central

Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

2013-01-01

Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

Neuromodulation, agency and autonomy.

PubMed

Glannon, Walter

2014-01-01

Neuromodulation consists in altering brain activity to restore mental and physical functions in individuals with neuropsychiatric disorders and brain and spinal cord injuries. This can be achieved by delivering electrical stimulation that excites or inhibits neural tissue, by using electrical signals in the brain to move computer cursors or robotic arms, or by displaying brain activity to subjects who regulate that activity by their own responses to it. As enabling prostheses, deep-brain stimulation and brain-computer interfaces (BCIs) are forms of extended embodiment that become integrated into the individual's conception of himself as an autonomous agent. In BCIs and neurofeedback, the success or failure of the techniques depends on the interaction between the learner and the trainer. The restoration of agency and autonomy through neuromodulation thus involves neurophysiological, psychological and social factors.

Functional connectivity and graph theory in preclinical Alzheimer's disease.

PubMed

Brier, Matthew R; Thomas, Jewell B; Fagan, Anne M; Hassenstab, Jason; Holtzman, David M; Benzinger, Tammie L; Morris, John C; Ances, Beau M

2014-04-01

Alzheimer's disease (AD) has a long preclinical phase in which amyloid and tau cerebral pathology accumulate without producing cognitive symptoms. Resting state functional connectivity magnetic resonance imaging has demonstrated that brain networks degrade during symptomatic AD. It is unclear to what extent these degradations exist before symptomatic onset. In this study, we investigated graph theory metrics of functional integration (path length), functional segregation (clustering coefficient), and functional distinctness (modularity) as a function of disease severity. Further, we assessed whether these graph metrics were affected in cognitively normal participants with cerebrospinal fluid evidence of preclinical AD. Clustering coefficient and modularity, but not path length, were reduced in AD. Cognitively normal participants who harbored AD biomarker pathology also showed reduced values in these graph measures, demonstrating brain changes similar to, but smaller than, symptomatic AD. Only modularity was significantly affected by age. We also demonstrate that AD has a particular effect on hub-like regions in the brain. We conclude that AD causes large-scale disconnection that is present before onset of symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

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 reparative processes in patient groups that have divergent functional outcome, with the ultimate goal of developing targeted therapeutic agents.

Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

PubMed Central

Simmons, Camilla; Mesquita, Michel B.; Wood, Tobias C.; Williams, Steve C. R.; Vernon, Anthony C.; Cash, Diana

2017-01-01

Resting-state functional MRI (rsfMRI) is an imaging technology that has recently gained attention for its ability to detect disruptions in functional brain networks in humans, including in patients with Parkinson’s disease (PD), revealing early and widespread brain network abnormalities. This methodology is now readily applicable to experimental animals offering new possibilities for cross-species translational imaging. In this context, we herein describe the application of rsfMRI to the unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat, a robust experimental model of the dopamine depletion implicated in PD. Using graph theory to analyse the rsfMRI data, we were able to provide meaningful and translatable measures of integrity, influence and segregation of the underlying functional brain architecture. Specifically, we confirm that rats share a similar functional brain network topology as observed in humans, characterised by small-worldness and modularity. Interestingly, we observed significantly reduced functional connectivity in the 6-OHDA rats, primarily in the ipsilateral (lesioned) hemisphere as evidenced by significantly lower node degree, local efficiency and clustering coefficient in the motor, orbital and sensorimotor cortices. In contrast, we found significantly, and bilaterally, increased thalamic functional connectivity in the lesioned rats. The unilateral deficits in the cortex are consistent with the unilateral nature of this model and further support the validity of the rsfMRI technique in rodents. We thereby provide a methodological framework for the investigation of brain networks in other rodent experimental models of PD, as well as of animal models in general, for cross-comparison with human data. PMID:28249008

Small-world human brain networks: Perspectives and challenges.

PubMed

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

2017-06-01

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

Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

PubMed

Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

2014-04-01

Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat

PubMed Central

Lopez, David Fernandez; Faustino, Joel; Daneman, Richard; Zhou, Lu; Lee, Sarah; Derugin, Nikita; Wendland, Michael F.; Vexler, Zinaida S

2012-01-01

The immaturity of the CNS at birth greatly affects injury after stroke but the contribution of the blood-brain barrier (BBB) to the differential response to stroke in adults and neonates is poorly understood. We asked if the structure and function of the BBB is disrupted differently in neonatal and adult rats by transient middle cerebral artery occlusion. In adult rats, albumin leakage into injured regions was markedly increased during 2–24 h reperfusion but leakage remained low in the neonates. Functional assays employing intravascular tracers in the neonates showed that BBB permeability to both large (70-kDa dextran) and small (3-kDa dextran, Gd-DTPA) tracers remained largely undisturbed 24h after reperfusion. The profoundly different functional integrity of the BBB was associated with the largely nonoverlapping patterns of regulated genes in endothelial cells purified from injured and uninjured adult and neonatal brain at 24h (endothelial transcriptome, 31,042 total probe sets). Within significantly regulated 1,266 probe sets in injured adults and 361 probe sets in neonates, changes in the gene expression of the basal lamina components, adhesion molecules, the tight junction protein occludin, and MMP-9 were among the key differences. The protein expression of collagen-IV, laminin, claudin-5, occludin and ZO-1 was also better preserved in neonatal rats. Neutrophil infiltration remained low in acutely injured neonates but neutralization of CINC-1 in the systemic circulation enhanced neutrophil infiltration, BBB permeability and injury. The markedly more integrant BBB in neonatal brain than in adult brain after acute stroke may have major implications for the treatment of neonatal stroke. PMID:22787045

Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

PubMed

Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

2016-08-01

The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Edaravone Protects against Methylglyoxal-Induced Barrier Damage in Human Brain Endothelial Cells

PubMed Central

Tóth, Andrea E.; Walter, Fruzsina R.; Bocsik, Alexandra; Sántha, Petra; Veszelka, Szilvia; Nagy, Lajos; Puskás, László G.; Couraud, Pierre-Olivier; Takata, Fuyuko; Dohgu, Shinya; Kataoka, Yasufumi; Deli, Mária A.

2014-01-01

Background Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. PMID:25033388

Hierarchical Brain Networks Active in Approach and Avoidance Goal Pursuit

PubMed Central

Spielberg, Jeffrey M.; Heller, Wendy; Miller, Gregory A.

2013-01-01

Effective approach/avoidance goal pursuit is critical for attaining long-term health and well-being. Research on the neural correlates of key goal-pursuit processes (e.g., motivation) has long been of interest, with lateralization in prefrontal cortex being a particularly fruitful target of investigation. However, this literature has often been limited by a lack of spatial specificity and has not delineated the precise aspects of approach/avoidance motivation involved. Additionally, the relationships among brain regions (i.e., network connectivity) vital to goal-pursuit remain largely unexplored. Specificity in location, process, and network relationship is vital for moving beyond gross characterizations of function and identifying the precise cortical mechanisms involved in motivation. The present paper integrates research using more spatially specific methodologies (e.g., functional magnetic resonance imaging) with the rich psychological literature on approach/avoidance to propose an integrative network model that takes advantage of the strengths of each of these literatures. PMID:23785328

Hierarchical brain networks active in approach and avoidance goal pursuit.

PubMed

Spielberg, Jeffrey M; Heller, Wendy; Miller, Gregory A

2013-01-01

Effective approach/avoidance goal pursuit is critical for attaining long-term health and well-being. Research on the neural correlates of key goal-pursuit processes (e.g., motivation) has long been of interest, with lateralization in prefrontal cortex being a particularly fruitful target of investigation. However, this literature has often been limited by a lack of spatial specificity and has not delineated the precise aspects of approach/avoidance motivation involved. Additionally, the relationships among brain regions (i.e., network connectivity) vital to goal-pursuit remain largely unexplored. Specificity in location, process, and network relationship is vital for moving beyond gross characterizations of function and identifying the precise cortical mechanisms involved in motivation. The present paper integrates research using more spatially specific methodologies (e.g., functional magnetic resonance imaging) with the rich psychological literature on approach/avoidance to propose an integrative network model that takes advantage of the strengths of each of these literatures.

Biological Risk for the Development of Problem Behavior in Adolescence: Integrating Insights from Behavioral Genetics and Neuroscience.

PubMed

Harden, K Paige; Mann, Frank D

2015-12-01

Adolescence is a time of increasing engagement in a variety of problem behaviors, including substance use and delinquency. Genetic risk for problem behavior increases over adolescence, is mediated partially by individual differences in sensation seeking, and is exacerbated by involvement with deviant peers. In this article, we describe how findings from behavioral genetic research on problem behavior intersect with research from developmental neuroscience. In particular, the incentive-processing system, including the ventral striatum, responds increasingly to rewards in adolescence, particularly in peer contexts. This developmental shift may be influenced by hormonal changes at puberty. Individual differences in the structure and function of reward-responsive brain regions may be intermediary phenotypes that mediate adolescents' genetic risk for problem behavior. The study of problem behavior can be enriched by interdisciplinary research that integrates measures of brain structure and function into genetically informed studies.

Magnetoencephalography in ellipsoidal geometry

NASA Astrophysics Data System (ADS)

Dassios, George; Kariotou, Fotini

2003-01-01

An exact analytic solution for the forward problem in the theory of biomagnetics of the human brain is known only for the (1D) case of a sphere and the (2D) case of a spheroid, where the excitation field is due to an electric dipole within the corresponding homogeneous conductor. In the present work the corresponding problem for the more realistic ellipsoidal brain model is solved and the leading quadrupole approximation for the exterior magnetic field is obtained in a form that exhibits the anisotropic character of the ellipsoidal geometry. The results are obtained in a straightforward manner through the evaluation of the interior electric potential and a subsequent calculation of the surface integral over the ellipsoid, using Lamé functions and ellipsoidal harmonics. The basic formulas are expressed in terms of the standard elliptic integrals that enter the expressions for the exterior Lamé functions. The laborious task of reducing the results to the spherical geometry is also included.

Dissociable prefrontal brain systems for attention and emotion

NASA Astrophysics Data System (ADS)

Yamasaki, Hiroshi; Labar, Kevin S.; McCarthy, Gregory

2002-08-01

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders. novelty | prefrontal cortex | amygdala | cingulate gyrus

Reduced prefrontal connectivity in psychopathy.

PubMed

Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

2011-11-30

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

Reduced Prefrontal Connectivity in Psychopathy

PubMed Central

Motzkin, Julian C.; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael

2012-01-01

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy. PMID:22131397

Individual classification of ADHD patients by integrating multiscale neuroimaging markers and advanced pattern recognition techniques

PubMed Central

Cheng, Wei; Ji, Xiaoxi; Zhang, Jie; Feng, Jianfeng

2012-01-01

Accurate classification or prediction of the brain state across individual subject, i.e., healthy, or with brain disorders, is generally a more difficult task than merely finding group differences. The former must be approached with highly informative and sensitive biomarkers as well as effective pattern classification/feature selection approaches. In this paper, we propose a systematic methodology to discriminate attention deficit hyperactivity disorder (ADHD) patients from healthy controls on the individual level. Multiple neuroimaging markers that are proved to be sensitive features are identified, which include multiscale characteristics extracted from blood oxygenation level dependent (BOLD) signals, such as regional homogeneity (ReHo) and amplitude of low-frequency fluctuations. Functional connectivity derived from Pearson, partial, and spatial correlation is also utilized to reflect the abnormal patterns of functional integration, or, dysconnectivity syndromes in the brain. These neuroimaging markers are calculated on either voxel or regional level. Advanced feature selection approach is then designed, including a brain-wise association study (BWAS). Using identified features and proper feature integration, a support vector machine (SVM) classifier can achieve a cross-validated classification accuracy of 76.15% across individuals from a large dataset consisting of 141 healthy controls and 98 ADHD patients, with the sensitivity being 63.27% and the specificity being 85.11%. Our results show that the most discriminative features for classification are primarily associated with the frontal and cerebellar regions. The proposed methodology is expected to improve clinical diagnosis and evaluation of treatment for ADHD patient, and to have wider applications in diagnosis of general neuropsychiatric disorders. PMID:22888314

Estimating the Integrated Information Measure Phi from High-Density Electroencephalography during States of Consciousness in Humans

PubMed Central

Kim, Hyoungkyu; Hudetz, Anthony G.; Lee, Joseph; Mashour, George A.; Lee, UnCheol; Avidan, Michael S.

2018-01-01

The integrated information theory (IIT) proposes a quantitative measure, denoted as Φ, of the amount of integrated information in a physical system, which is postulated to have an identity relationship with consciousness. IIT predicts that the value of Φ estimated from brain activities represents the level of consciousness across phylogeny and functional states. Practical limitations, such as the explosive computational demands required to estimate Φ for real systems, have hindered its application to the brain and raised questions about the utility of IIT in general. To achieve practical relevance for studying the human brain, it will be beneficial to establish the reliable estimation of Φ from multichannel electroencephalogram (EEG) and define the relationship of Φ to EEG properties conventionally used to define states of consciousness. In this study, we introduce a practical method to estimate Φ from high-density (128-channel) EEG and determine the contribution of each channel to Φ. We examine the correlation of power, frequency, functional connectivity, and modularity of EEG with regional Φ in various states of consciousness as modulated by diverse anesthetics. We find that our approximation of Φ alone is insufficient to discriminate certain states of anesthesia. However, a multi-dimensional parameter space extended by four parameters related to Φ and EEG connectivity is able to differentiate all states of consciousness. The association of Φ with EEG connectivity during clinically defined anesthetic states represents a new practical approach to the application of IIT, which may be used to characterize various physiological (sleep), pharmacological (anesthesia), and pathological (coma) states of consciousness in the human brain. PMID:29503611

Estimating the Integrated Information Measure Phi from High-Density Electroencephalography during States of Consciousness in Humans.

PubMed

Kim, Hyoungkyu; Hudetz, Anthony G; Lee, Joseph; Mashour, George A; Lee, UnCheol

2018-01-01

The integrated information theory (IIT) proposes a quantitative measure, denoted as Φ, of the amount of integrated information in a physical system, which is postulated to have an identity relationship with consciousness. IIT predicts that the value of Φ estimated from brain activities represents the level of consciousness across phylogeny and functional states. Practical limitations, such as the explosive computational demands required to estimate Φ for real systems, have hindered its application to the brain and raised questions about the utility of IIT in general. To achieve practical relevance for studying the human brain, it will be beneficial to establish the reliable estimation of Φ from multichannel electroencephalogram (EEG) and define the relationship of Φ to EEG properties conventionally used to define states of consciousness. In this study, we introduce a practical method to estimate Φ from high-density (128-channel) EEG and determine the contribution of each channel to Φ. We examine the correlation of power, frequency, functional connectivity, and modularity of EEG with regional Φ in various states of consciousness as modulated by diverse anesthetics. We find that our approximation of Φ alone is insufficient to discriminate certain states of anesthesia. However, a multi-dimensional parameter space extended by four parameters related to Φ and EEG connectivity is able to differentiate all states of consciousness. The association of Φ with EEG connectivity during clinically defined anesthetic states represents a new practical approach to the application of IIT, which may be used to characterize various physiological (sleep), pharmacological (anesthesia), and pathological (coma) states of consciousness in the human brain.

Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

PubMed

Svatkova, Alena; Mandl, René C W; Scheewe, Thomas W; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

2015-07-01

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or life-as-usual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

NASA Astrophysics Data System (ADS)

Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

2016-10-01

Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

Human brain distinctiveness based on EEG spectral coherence connectivity.

PubMed

Rocca, D La; Campisi, P; Vegso, B; Cserti, P; Kozmann, G; Babiloni, F; Fallani, F De Vico

2014-09-01

The use of EEG biometrics, for the purpose of automatic people recognition, has received increasing attention in the recent years. Most of the current analyses rely on the extraction of features characterizing the activity of single brain regions, like power spectrum estimation, thus neglecting possible temporal dependencies between the generated EEG signals. However, important physiological information can be extracted from the way different brain regions are functionally coupled. In this study, we propose a novel approach that fuses spectral coherence-based connectivity between different brain regions as a possibly viable biometric feature. The proposed approach is tested on a large dataset of subjects (N = 108) during eyes-closed (EC) and eyes-open (EO) resting state conditions. The obtained recognition performance shows that using brain connectivity leads to higher distinctiveness with respect to power-spectrum measurements, in both the experimental conditions. Notably, a 100% recognition accuracy is obtained in EC and EO when integrating functional connectivity between regions in the frontal lobe, while a lower 97.5% is obtained in EC (96.26% in EO) when fusing power spectrum information from parieto-occipital (centro-parietal in EO) regions. Taken together, these results suggest that the functional connectivity patterns represent effective features for improving EEG-based biometric systems.

Anticholinesterase Effect on Motor Kinematic Measures and Brain Activation in Parkinson’s Disease

PubMed Central

Mentis, Marc J.; Delalot, Dominique; Naqvi, Hassan; Gordon, Mark F.; Gudesblatt, Mark; Edwards, Christine; Donatelli, Luke; Dhawan, Vijay; Eidelberg, David

2015-01-01

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson’s disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity. PMID:16228997

Multisensory integration mechanisms during aging

PubMed Central

Freiherr, Jessica; Lundström, Johan N.; Habel, Ute; Reetz, Kathrin

2013-01-01

The rapid demographical shift occurring in our society implies that understanding of healthy aging and age-related diseases is one of our major future challenges. Sensory impairments have an enormous impact on our lives and are closely linked to cognitive functioning. Due to the inherent complexity of sensory perceptions, we are commonly presented with a complex multisensory stimulation and the brain integrates the information from the individual sensory channels into a unique and holistic percept. The cerebral processes involved are essential for our perception of sensory stimuli and becomes especially important during the perception of emotional content. Despite ongoing deterioration of the individual sensory systems during aging, there is evidence for an increase in, or maintenance of, multisensory integration processing in aging individuals. Within this comprehensive literature review on multisensory integration we aim to highlight basic mechanisms and potential compensatory strategies the human brain utilizes to help maintain multisensory integration capabilities during healthy aging to facilitate a broader understanding of age-related pathological conditions. Further our goal was to identify where further research is needed. PMID:24379773

Audio-tactile integration and the influence of musical training.

PubMed

Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

2014-01-01

Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.

Mid-Task Break Improves Global Integration of Functional Connectivity in Lower Alpha Band

PubMed Central

Li, Junhua; Lim, Julian; Chen, Yu; Wong, Kianfoong; Thakor, Nitish; Bezerianos, Anastasios; Sun, Yu

2016-01-01

Numerous efforts have been devoted to revealing neurophysiological mechanisms of mental fatigue, aiming to find an effective way to reduce the undesirable fatigue-related outcomes. Until recently, mental fatigue is thought to be related to functional dysconnectivity among brain regions. However, the topological representation of brain functional connectivity altered by mental fatigue is only beginning to be revealed. In the current study, we applied a graph theoretical approach to analyse such topological alterations in the lower alpha band (8~10 Hz) of EEG data from 20 subjects undergoing a two-session experiment, in which one session includes four successive blocks with visual oddball tasks (session 1) whereas a mid-task break was introduced in the middle of four task blocks in the other session (session 2). Phase lag index (PLI) was then employed to measure functional connectivity strengths for all pairs of EEG channels. Behavior and connectivity maps were compared between the first and last task blocks in both sessions. Inverse efficiency scores (IES = reaction time/response accuracy) were significantly increased in the last task block, showing a clear effect of time-on-task in participants. Furthermore, a significant block-by-session interaction was revealed in the IES, suggesting the effectiveness of the mid-task break on maintaining task performance. More importantly, a significant session-independent deficit of global integration and an increase of local segregation were found in the last task block across both sessions, providing further support for the presence of a reshaped topology in functional brain connectivity networks under fatigue state. Moreover, a significant block-by-session interaction was revealed in the characteristic path length, small-worldness, and global efficiency, attributing to the significantly disrupted network topology in session 1 in comparison of the maintained network structure in session 2. Specifically, we found increased nodal betweenness centrality in several channels resided in frontal regions in session 1, resembling the observations of more segregated global architecture under fatigue state. Taken together, our findings provide insights into the substrates of brain functional dysconnectivity patterns for mental fatigue and reiterate the effectiveness of the mid-task break on maintaining brain network efficiency. PMID:27378894

Monotonic non-linear transformations as a tool to investigate age-related effects on brain white matter integrity: A Box-Cox investigation.

PubMed

Morozova, Maria; Koschutnig, Karl; Klein, Elise; Wood, Guilherme

2016-01-15

Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigating the Neural Correlates of Emotion–Cognition Interaction Using an Affective Stroop Task

PubMed Central

Raschle, Nora M.; Fehlbaum, Lynn V.; Menks, Willeke M.; Euler, Felix; Sterzer, Philipp; Stadler, Christina

2017-01-01

The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion–cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related brain regions, and therefore support previous findings investigating emotion–cognition interaction in healthy adults. Moreover, emotion and cognition seem to be tightly related to each other, as indicated by shared neural networks involved in both of these processes. Emotion processing, cognitive control, and their interaction are crucial for healthy functioning and a lack thereof is related to psychiatric disorders such as, disruptive behavior disorders. Future studies may investigate the neural characteristics of children and adolescents with disruptive behavior disorders. PMID:28919871

Neuroscience is awaiting for a breakthrough: an essay bridging the concepts of Descartes, Einstein, Heisenberg, Hebb and Hayek with the explanatory formulations in this special issue.

PubMed

Başar, Erol; Karakaş, Sirel

2006-05-01

The paper presents gedankenmodels which, based on the theories and models in the present special issue, describe the conditions for a breakthrough in brain sciences and neuroscience. The new model is based on contemporary findings which show that the brain and its cognitive processes show super-synchronization. Accordingly, understanding the brain/body-mind complex is possible only when these three are considered as a wholistic entity and not as discrete structures or functions. Such a breakthrough and the related perspectives to the brain/body-mind complex will involve a transition from the mechanistic Cartesian system to a nebulous Cartesian system, one that is basically characterized by parallel computing and is further parallel to quantum mechanics. This integrated outlook on the brain/body-mind, or dynamic functionality, will make the treatment of also the meta-cognitive processes and the greater part of the iceberg, the unconscious, possible. All this will be possible only through the adoption of a multidisciplinary approach that will bring together the knowledge and the technology of the four P's which consist of physics, physiology, psychology and philosophy. The genetic approach to the functional dynamics of the brain/body-mind, where the oscillatory responses were found to be laws of brain activity, is presented in this volume as one of the most recent perspectives of neuroscience.

Hand in glove: brain and skull in development and dysmorphogenesis

PubMed Central

Flaherty, Kevin

2013-01-01

The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease. PMID:23525521

Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model

PubMed Central

On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.

2013-01-01

The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors.

PubMed

Guo, Lu; Wang, Gang; Feng, Yuanming; Yu, Tonggang; Guo, Yu; Bai, Xu; Ye, Zhaoxiang

2016-09-21

Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images.

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

PubMed Central

2016-01-01

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

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

PubMed

Li, Guangye; Zhang, Dingguo

2016-01-01

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

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

PubMed

Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Shanshan; Wang, Lubin; Yang, Zheng; Li, Shi-Jiang; Binder, Jeffrey R; Hudetz, Anthony G

2018-05-08

The level and richness of consciousness depend on information integration in the brain. Altered interregional functional interactions may indicate disrupted information integration during anesthetic-induced unconsciousness. How anesthetics modulate the amount of information in various brain regions has received less attention. Here, we propose a novel approach to quantify regional information content in the brain by the entropy of the principal components of regional blood oxygen-dependent imaging signals during graded propofol sedation. Fifteen healthy individuals underwent resting-state scans in wakeful baseline, light sedation (conscious), deep sedation (unconscious), and recovery (conscious). Light sedation characterized by lethargic behavioral responses was associated with global reduction of entropy in the brain. Deep sedation with completely suppressed overt responsiveness was associated with further reductions of entropy in sensory (primary and higher sensory plus orbital prefrontal cortices) but not high-order cognitive (dorsal and medial prefrontal, cingulate, parietotemporal cortices and hippocampal areas) systems. Upon recovery of responsiveness, entropy was restored in the sensory but not in high-order cognitive systems. These findings provide novel evidence for a reduction of information content of the brain as a potential systems-level mechanism of reduced consciousness during propofol anesthesia. The differential changes of entropy in the sensory and high-order cognitive systems associated with losing and regaining overt responsiveness are consistent with the notion of "disconnected consciousness", in which a complete sensory-motor disconnection from the environment occurs with preserved internal mentation.

Neurophotonics: optical methods to study and control the brain

NASA Astrophysics Data System (ADS)

Doronina-Amitonova, L. V.; Fedotov, I. V.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2015-04-01

Methods of optical physics offer unique opportunities for the investigation of brain and higher nervous activity. The integration of cutting-edge laser technologies and advanced neurobiology opens a new cross-disciplinary area of natural sciences - neurophotonics - focusing on the development of a vast arsenal of tools for functional brain diagnostics, stimulation of individual neurons and neural networks, and the molecular engineering of brain cells aimed at the diagnosis and therapy of neurodegenerative and psychic diseases. Optical fibers help to confront the most challenging problems in brain research, including the analysis of molecular-cellular mechanisms of the formation of memory and behavior. New generation optical fibers provide new solutions for the development of fundamentally new, unique tools for neurophotonics and laser neuroengineering - fiber-optic neuroendoscopes and neurointerfaces. These instruments broaden research horizons when investigating the most complex brain functions, enabling a long-term multiplex detection of fluorescent protein markers, as well as photostimulation of neuronal activity in deep brain areas in living, freely moving animals with an unprecedented spatial resolution and minimal invasiveness. This emerging technology opens new horizons for understanding learning and long-term memory through experiments with living, freely moving mammals. Here, we present a brief review of this rapidly growing field of research.

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

PubMed

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

2017-04-01

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

Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

PubMed

Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

2018-06-01

TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

A Functional Cartography of Cognitive Systems

PubMed Central

Mattar, Marcelo G.; Cole, Michael W.; Thompson-Schill, Sharon L.; Bassett, Danielle S.

2015-01-01

One of the most remarkable features of the human brain is its ability to adapt rapidly and efficiently to external task demands. Novel and non-routine tasks, for example, are implemented faster than structural connections can be formed. The neural underpinnings of these dynamics are far from understood. Here we develop and apply novel methods in network science to quantify how patterns of functional connectivity between brain regions reconfigure as human subjects perform 64 different tasks. By applying dynamic community detection algorithms, we identify groups of brain regions that form putative functional communities, and we uncover changes in these groups across the 64-task battery. We summarize these reconfiguration patterns by quantifying the probability that two brain regions engage in the same network community (or putative functional module) across tasks. These tools enable us to demonstrate that classically defined cognitive systems—including visual, sensorimotor, auditory, default mode, fronto-parietal, cingulo-opercular and salience systems—engage dynamically in cohesive network communities across tasks. We define the network role that a cognitive system plays in these dynamics along the following two dimensions: (i) stability vs. flexibility and (ii) connected vs. isolated. The role of each system is therefore summarized by how stably that system is recruited over the 64 tasks, and how consistently that system interacts with other systems. Using this cartography, classically defined cognitive systems can be categorized as ephemeral integrators, stable loners, and anything in between. Our results provide a new conceptual framework for understanding the dynamic integration and recruitment of cognitive systems in enabling behavioral adaptability across both task and rest conditions. This work has important implications for understanding cognitive network reconfiguration during different task sets and its relationship to cognitive effort, individual variation in cognitive performance, and fatigue. PMID:26629847

Diffusion Tensor Imaging in Relation to Cognitive and Functional Outcome of Traumatic Brain Injury in Children

PubMed Central

Levin, Harvey S.; Wilde, Elisabeth A.; Chu, Zili; Yallampalli, Ragini; Hanten, Gerri R.; Li, Xiaoqi; Chia, Jon; Vasquez, Carmen; Hunter, Jill V.

2008-01-01

Objective To investigate the relation of white matter integrity using diffusion tensor imaging (DTI) to cognitive and functional outcome of moderate to severe traumatic brain injury (TBI) in children. Design Prospective observational study of children who had sustained moderate to severe TBI and a comparison group of children who had sustained orthopedic injury (OI). Participants Thirty-two children who had sustained moderate to severe TBI and 36 children with OI were studied. Methods Fiber tracking analysis of DTI acquired at 3-month postinjury and assessment of global outcome and cognitive function within 2 weeks of brain imaging. Global outcome was assessed using the Glasgow Outcome Scale and the Flanker task was used to measure cognitive processing speed and resistance to interference. Results Fractional anisotropy and apparent diffusion coefficient values differentiated the groups and both cognitive and functional outcome measures were related to the DTI findings. Dissociations were present wherein the relation of Fractional anisotropy to cognitive performance differed between the TBI and OI groups. A DTI composite measure of white matter integrity was related to global outcome in the children with TBI. Conclusions DTI is sensitive to white matter injury at 3 months following moderate to severe TBI in children, including brain regions that appear normal on conventional magnetic resonance imaging. DTI measures reflecting diffusion of water parallel and perpendicular to white matter tracts as calculated by fiber tracking analysis are related to global outcome, cognitive processing speed, and speed of resolving interference in children with moderate to severe TBI. Longitudinal data are needed to determine whether these relations between DTI and neurobehavioral outcome of TBI in children persist at longer follow-up intervals. PMID:18650764

Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity.

PubMed

Rieckmann, Anna; Hedden, Trey; Younger, Alayna P; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L

2016-02-01

Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy.

PubMed

Bonilha, Leonardo; Tabesh, Ali; Dabbs, Kevin; Hsu, David A; Stafstrom, Carl E; Hermann, Bruce P; Lin, Jack J

2014-08-01

Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large-scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early-life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new-onset seizures and 28 healthy controls. Children with new-onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared with controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large-scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment. Copyright © 2014 Wiley Periodicals, Inc.

REGULATION OF MEMORY – FROM THE ADRENAL MEDULLA TO LIVER TO ASTROCYTES TO NEURONS1

PubMed Central

Gold, Paul E.

2014-01-01

Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, resulting in increased blood glucose levels. The increase in blood glucose provides additional energy substrates to the brain to buttress the processes needed for an experience to be learned and remembered. In part, it appears that the increased glucose may act in the brain in a manner akin to that evident in the liver, engaging glycogenolysis in astrocytes to provide an energy substrate, in this case lactate, to augment neuronal functions. Together, the findings reveal a mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes. PMID:24406469

Contributions of Philip Teitelbaum to affective neuroscience.

PubMed

Berridge, Kent C

2012-06-01

As part of a festschrift issue for Philip Teitelbaum, I offer here the thesis that Teitelbaum deserves to be viewed as an important forefather to the contemporary field of affective neuroscience (which studies motivation, emotion and affect in the brain). Teitelbaum's groundbreaking analyses of motivation deficits induced by lateral hypothalamic damage, of roles of food palatability in revealing residual function, and of recovery of 'lost' functions helped shape modern understanding of how motivation circuits operate within the brain. His redefinition of the minimum requirement for identifying motivation raised the conceptual bar for thinking about the topic among behavioral neuroscientists. His meticulous analyses of patterned stages induced by brain manipulations, life development and clinical disorders added new dimensions to our appreciation of how brain systems work. His steadfast highlighting of integrative functions and behavioral complexity helped provide a healthy functionalist counterbalance to reductionist trends in science of the late 20th century. In short, Philip Teitelbaum can be seen to have made remarkable contributions to several domains of psychology and neuroscience, including affective neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception.

PubMed

Grinvald, A

1992-01-01

Long standing questions related to brain mechanisms underlying perception can finally be resolved by direct visualization of the architecture and function of mammalian cortex. This advance has been accomplished with the aid of two optical imaging techniques with which one can literally see how the brain functions. The upbringing of this technology required a multi-disciplinary approach integrating brain research with organic chemistry, spectroscopy, biophysics, computer sciences, optics and image processing. Beyond the technological ramifications, recent research shed new light on cortical mechanisms underlying sensory perception. Clinical applications of this technology for precise mapping of the cortical surface of patients during neurosurgery have begun. Below is a brief summary of our own research and a description of the technical specifications of the two optical imaging techniques. Like every technique, optical imaging also suffers from severe limitations. Here we mostly emphasize some of its advantages relative to all alternative imaging techniques currently in use. The limitations are critically discussed in our recent reviews. For a series of other reviews, see Cohen (1989).

Contributions of Philip Teitelbaum to affective neuroscience

PubMed Central

Berridge, Kent C.

2011-01-01

As part of a festschrift issue for Philip Teitelbaum, I offer here the thesis that Teitelbaum deserves to be viewed as an important forefather to the contemporary field of affective neuroscience (which studies motivation, emotion and affect in the brain). Teitelbaum’s groundbreaking analyses of motivation deficits induced by lateral hypothalamic damage, of roles of food palatability in revealing residual function, and of recovery of ‘lost’ functions helped shape modern understanding of how motivation circuits operate within the brain. His redefinition of the minimum requirement for identifying motivation raised the conceptual bar for thinking about the topic among behavioral neuroscientists. His meticulous analyses of patterned stages induced by brain manipulations, life development and clinical disorders added new dimensions to our appreciation of how brain systems work. His steadfast highlighting of integrative functions and behavioral complexity helped provide a healthy functionalist counterbalance to reductionist trends in science of the late 20th century. In short, Philip Teitelbaum can be seen to have made remarkable contributions to several domains of psychology and neuroscience, including affective neuroscience. PMID:22051942

Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

PubMed Central

Naylor, Andrew S.; Bull, Cecilia; Nilsson, Marie K. L.; Zhu, Changlian; Björk-Eriksson, Thomas; Eriksson, Peter S.; Blomgren, Klas; Kuhn, H. Georg

2008-01-01

Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors. PMID:18765809

What We Know About the Brain Structure-Function Relationship.

PubMed

Batista-García-Ramó, Karla; Fernández-Verdecia, Caridad Ivette

2018-04-18

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.

Neurosurgical sapphire handheld probe for intraoperative optical diagnostics, laser coagulation and aspiration of malignant brain tissue

NASA Astrophysics Data System (ADS)

Shikunova, Irina A.; Zaytsev, Kirill I.; Stryukov, Dmitrii O.; Dubyanskaya, Evgenia N.; Kurlov, Vladimir N.

2017-07-01

In this paper, a handheld contact probe based on sapphire shaped crystal was developed for the intraoperative optical diagnosis and aspiration of malignant brain tissue combined with the laser hemostasis. Such a favorable combination of several functions in a single instrument significantly increases its clinical relevance. It makes possible highly-accurate real-time detection and removal of either large-scale malignancies or even separate invasive cancer cells. The proposed neuroprobe was integrated into the clinical neurosurgical workflow for the intraoperative fluorescence identification and removal of malignant tissues of the brain.

Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia.

PubMed

Langen, Carolyn D; White, Tonya; Ikram, M Arfan; Vernooij, Meike W; Niessen, Wiro J

2015-01-01

Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only fractional anisotropy and mean correlation showed regional differences. The presented visualizations were helpful in comparing and evaluating connectivity measures on multiple levels in both studies.

Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence?

PubMed

Bos, Dienke J; van Montfort, Simone J T; Oranje, Bob; Durston, Sarah; Smeets, Paul A M

2016-03-01

Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

All‐optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI

PubMed Central

Sha, Fern; Johenning, Friedrich W.; Schreiter, Eric R.; Looger, Loren L.; Larkum, Matthew E.

2016-01-01

Key points The genetically encoded fluorescent calcium integrator calcium‐modulated photoactivatable ratiobetric integrator (CaMPARI) reports calcium influx induced by synaptic and neural activity. Its fluorescence is converted from green to red in the presence of violet light and calcium.The rate of conversion – the sensitivity to activity – is tunable and depends on the intensity of violet light.Synaptic activity and action potentials can independently initiate significant CaMPARI conversion.The level of conversion by subthreshold synaptic inputs is correlated to the strength of input, enabling optical readout of relative synaptic strength.When combined with optogenetic activation of defined presynaptic neurons, CaMPARI provides an all‐optical method to map synaptic connectivity. Abstract The calcium‐modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded calcium integrator that facilitates the study of neural circuits by permanently marking cells active during user‐specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labelling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all‐optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and subthreshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed CaMPARI and optogenetics for functional circuit mapping in ex vivo acute brain slices, which preserve in vivo‐like connectivity of axon terminals. With a single light source, we stimulated channelrhodopsin‐2‐expressing long‐range posteromedial (POm) thalamic axon terminals in cortex and induced CaMPARI conversion in recipient cortical neurons. We found that POm stimulation triggers robust photoconversion of layer 5 cortical neurons and weaker conversion of layer 2/3 neurons. Thus, CaMPARI enables network‐wide, tunable, all‐optical functional circuit mapping that captures supra‐ and subthreshold depolarization. PMID:27861906

The Integrity of the Corpus Callosum Mitigates the Impact of Blood Pressure on the Ventral Attention Network and Information Processing Speed in Healthy Adults

PubMed Central

Wong, Nichol M. L.; Ma, Ernie Po-Wing; Lee, Tatia M. C.

2017-01-01

Hypertension is a risk factor for cognitive impairment in older age. However, evidence of the neural basis of the relationship between the deterioration of cognitive function and elevated blood pressure is sparse. Based on previous research, we speculate that variations in brain connectivity are closely related to elevated blood pressure even before the onset of clinical conditions and apparent cognitive decline in individuals over 60 years of age. Forty cognitively healthy adults were recruited. Each received a blood pressure test before and after the cognitive assessment in various domains. Diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were collected. Our findings confirm that elevated blood pressure is associated with brain connectivity variations in cognitively healthy individuals. The integrity of the splenium of the corpus callosum is closely related to individual differences in systolic blood pressure. In particular, elevated systolic blood pressure is related to resting-state ventral attention network (VAN) and information processing speed. Serial mediation analyses have further revealed that lower integrity of the splenium statistically predicts elevated systolic blood pressure, which in turn predicts weakened functional connectivity (FC) within the VAN and eventually poorer processing speed. The current study sheds light on how neural correlates are involved in the impact of elevated blood pressure on cognitive functioning. PMID:28484386

Social Behavior and Impairments in Social Cognition Following Traumatic Brain Injury.

PubMed

May, Michelle; Milders, Maarten; Downey, Bruce; Whyte, Maggie; Higgins, Vanessa; Wojcik, Zuzana; Amin, Sophie; O'Rourke, Suzanne

2017-05-01

The negative effect of changes in social behavior following traumatic brain injury (TBI) are known, but much less is known about the neuropsychological impairments that may underlie and predict these changes. The current study investigated possible associations between post-injury behavior and neuropsychological competencies of emotion recognition, understanding intentions, and response selection, that have been proposed as important for social functioning. Forty participants with TBI and 32 matched healthy participants completed a battery of tests assessing the three functions of interest. In addition, self- and proxy reports of pre- and post-injury behavior, mood, and community integration were collected. The TBI group performed significantly poorer than the comparison group on all tasks of emotion recognition, understanding intention, and on one task of response selection. Ratings of current behavior suggested significant changes in the TBI group relative to before the injury and showed significantly poorer community integration and interpersonal behavior than the comparison group. Of the three functions considered, emotion recognition was associated with both post-injury behavior and community integration and this association could not be fully explained by injury severity, time since injury, or education. The current study confirmed earlier findings of associations between emotion recognition and post-TBI behavior, providing partial evidence for models proposing emotion recognition as one of the pre-requisites for adequate social functioning. (JINS, 2017, 23, 400-411).

Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

PubMed

Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

2016-02-01

A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Spatially Regularized Machine Learning for Task and Resting-state fMRI

PubMed Central

Song, Xiaomu; Panych, Lawrence P.; Chen, Nan-kuei

2015-01-01

Background Reliable mapping of brain function across sessions and/or subjects in task- and resting-state has been a critical challenge for quantitative fMRI studies although it has been intensively addressed in the past decades. New Method A spatially regularized support vector machine (SVM) technique was developed for the reliable brain mapping in task- and resting-state. Unlike most existing SVM-based brain mapping techniques, which implement supervised classifications of specific brain functional states or disorders, the proposed method performs a semi-supervised classification for the general brain function mapping where spatial correlation of fMRI is integrated into the SVM learning. The method can adapt to intra- and inter-subject variations induced by fMRI nonstationarity, and identify a true boundary between active and inactive voxels, or between functionally connected and unconnected voxels in a feature space. Results The method was evaluated using synthetic and experimental data at the individual and group level. Multiple features were evaluated in terms of their contributions to the spatially regularized SVM learning. Reliable mapping results in both task- and resting-state were obtained from individual subjects and at the group level. Comparison with Existing Methods A comparison study was performed with independent component analysis, general linear model, and correlation analysis methods. Experimental results indicate that the proposed method can provide a better or comparable mapping performance at the individual and group level. Conclusions The proposed method can provide accurate and reliable mapping of brain function in task- and resting-state, and is applicable to a variety of quantitative fMRI studies. PMID:26470627

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

PubMed Central

Horowitz, Alana M.; Villeda, Saul A.

2017-01-01

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

PubMed

Abé, C; Rolstad, S; Petrovic, P; Ekman, C-J; Sparding, T; Ingvar, M; Landén, M

2018-06-15

Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

The neural circuits of innate fear: detection, integration, action, and memorization

PubMed Central

Silva, Bianca A.; Gross, Cornelius T.

2016-01-01

How fear is represented in the brain has generated a lot of research attention, not only because fear increases the chances for survival when appropriately expressed but also because it can lead to anxiety and stress-related disorders when inadequately processed. In this review, we summarize recent progress in the understanding of the neural circuits processing innate fear in rodents. We propose that these circuits are contained within three main functional units in the brain: a detection unit, responsible for gathering sensory information signaling the presence of a threat; an integration unit, responsible for incorporating the various sensory information and recruiting downstream effectors; and an output unit, in charge of initiating appropriate bodily and behavioral responses to the threatful stimulus. In parallel, the experience of innate fear also instructs a learning process leading to the memorization of the fearful event. Interestingly, while the detection, integration, and output units processing acute fear responses to different threats tend to be harbored in distinct brain circuits, memory encoding of these threats seems to rely on a shared learning system. PMID:27634145

Typical and atypical brain development: a review of neuroimaging studies

PubMed Central

Dennis, Emily L.; Thompson, Paul M.

2013-01-01

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders. PMID:24174907

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

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535