Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

PubMed

Moreno-López, Laura; Soriano-Mas, Carles; Delgado-Rico, Elena; Rio-Valle, Jacqueline S; Verdejo-García, Antonio

2012-01-01

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

Childhood adversity is linked to differential brain volumes in adolescents with alcohol use disorder: a voxel-based morphometry study.

PubMed

Brooks, Samantha J; Dalvie, Shareefa; Cuzen, Natalie L; Cardenas, Valerie; Fein, George; Stein, Dan J

2014-06-01

Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.

Neuroimaging explanations of age-related differences in task performance.

PubMed

Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

2014-01-01

Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance.

Gray Matter Volume in Adolescent Anxiety: An Impact of the Brain-Derived Neurotrophic Factor Val[superscript 66]Met Polymorphism?

ERIC Educational Resources Information Center

Mueller, Sven C.; Aouidad, Aveline; Gorodetsky, Elena; Goldman, David; Pine, Daniel S.; Ernst, Monique

2013-01-01

Objective: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val[superscript 66]Met polymorphism may modulate such brain morphometry profiles. Method: Using voxel-based…

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

Neural correlates of trust.

PubMed

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-12-11

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.

Neural correlates of trust

PubMed Central

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-01-01

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species. PMID:18056800

Understanding brain networks and brain organization

PubMed Central

Pessoa, Luiz

2014-01-01

What is the relationship between brain and behavior? The answer to this question necessitates characterizing the mapping between structure and function. The aim of this paper is to discuss broad issues surrounding the link between structure and function in the brain that will motivate a network perspective to understanding this question. As others in the past, I argue that a network perspective should supplant the common strategy of understanding the brain in terms of individual regions. Whereas this perspective is needed for a fuller characterization of the mind-brain, it should not be viewed as panacea. For one, the challenges posed by the many-to-many mapping between regions and functions is not dissolved by the network perspective. Although the problem is ameliorated, one should not anticipate a one-to-one mapping when the network approach is adopted. Furthermore, decomposition of the brain network in terms of meaningful clusters of regions, such as the ones generated by community-finding algorithms, does not by itself reveal “true” subnetworks. Given the hierarchical and multi-relational relationship between regions, multiple decompositions will offer different “slices” of a broader landscape of networks within the brain. Finally, I described how the function of brain regions can be characterized in a multidimensional manner via the idea of diversity profiles. The concept can also be used to describe the way different brain regions participate in networks. PMID:24819881

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

Exploring the Associations Between Intrinsic Brain Connectivity and Creative Ability Using Functional Connectivity Strength and Connectome Analysis.

PubMed

Gao, Zhenni; Zhang, Delong; Liang, Aiying; Liang, Bishan; Wang, Zengjian; Cai, Yuxuan; Li, Junchao; Gao, Mengxia; Liu, Xiaojin; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

2017-11-01

The present study aimed to explore the association between resting-state functional connectivity and creativity ability. Toward this end, the figural Torrance Tests of Creative Thinking (TTCT) scores were collected from 180 participants. Based on the figural TTCT measures, we collected resting-state functional magnetic resonance imaging data for participants with two different levels of creativity ability (a high-creativity group [HG, n = 22] and a low-creativity group [LG, n = 20]). For the aspect of group difference, this study combined voxel-wise functional connectivity strength (FCS) and seed-based functional connectivity to identify brain regions with group-change functional connectivity. Furthermore, the connectome properties of the identified regions and their associations with creativity were investigated using the permutation test, discriminative analysis, and brain-behavior correlation analysis. The results indicated that there were 4 regions with group differences in FCS, and these regions were linked to 30 other regions, demonstrating different functional connectivity between the groups. Together, these regions form a creativity-related network, and we observed higher network efficiency in the HG compared with the LG. The regions involved in the creativity network were widely distributed across the modality-specific/supramodality cerebral cortex, subcortex, and cerebellum. Notably, properties of regions in the supramodality networks (i.e., the default mode network and attention network) carried creativity-level discriminative information and were significantly correlated with the creativity performance. Together, these findings demonstrate a link between intrinsic brain connectivity and creative ability, which should provide new insights into the neural basis of creativity.

EEG functional connectivity, axon delays and white matter disease.

PubMed

Nunez, Paul L; Srinivasan, Ramesh; Fields, R Douglas

2015-01-01

Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

Working memory brain activity and capacity link MAOA polymorphism to aggressive behavior during development

PubMed Central

Ziermans, T; Dumontheil, I; Roggeman, C; Peyrard-Janvid, M; Matsson, H; Kere, J; Klingberg, T

2012-01-01

A developmental increase in working memory capacity is an important part of cognitive development, and low working memory (WM) capacity is a risk factor for developing psychopathology. Brain activity represents a promising endophenotype for linking genes to behavior and for improving our understanding of the neurobiology of WM development. We investigated gene–brain–behavior relationships by focusing on 18 single-nucleotide polymorphisms (SNPs) located in six dopaminergic candidate genes (COMT, SLC6A3/DAT1, DBH, DRD4, DRD5, MAOA). Visuospatial WM (VSWM) brain activity, measured with functional magnetic resonance imaging, and VSWM capacity were assessed in a longitudinal study of typically developing children and adolescents. Behavioral problems were evaluated using the Child Behavior Checklist (CBCL). One SNP (rs6609257), located ∼6.6 kb downstream of the monoamine oxidase A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms. There were no direct significant correlations between rs6609257 and behavioral symptoms. These results suggest a mediating role of WM brain activity and capacity in linking the MAOA gene to aggressive behavior during development. PMID:22832821

Joint brain connectivity estimation from diffusion and functional MRI data

NASA Astrophysics Data System (ADS)

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

2015-03-01

Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information flow is introduced and used to model the propagation of information between GM areas through WM fiber bundles. The link capacity, i.e., ability to transfer information, is characterized by the relative strength of fiber bundles, e.g., fiber count gathered from the tractography of dMRI data. The node information demand is considered to be proportional to the correlation between neural activity at various cortical areas involved in a particular functional mode (e.g. visual, motor, etc.). These two properties lead to the link capacity and node demand constraints in the proposed model. Moreover, the information flow of a link cannot exceed the demand from either end node. This is captured by the feasibility constraints. Two different cost functions are considered in the optimization formulation in this paper. The first cost function, the reciprocal of fiber strength represents the unit cost for information passing through the link. In the second cost function, a min-max (minimizing the maximal link load) approach is used to balance the usage of each link. Optimizing the first cost function selects the pathway with strongest fiber strength for information propagation. In the second case, the optimization procedure finds all the possible propagation pathways and allocates the flow proportionally to their strength. Additionally, a penalty term is incorporated with both the cost functions to capture the possible missing and weak anatomical connections. With this set of constraints and the proposed cost functions, solving the network optimization problem recovers missing and weak anatomical connections supported by the functional information and provides the functional-associated anatomical subnetworks. Feasibility is demonstrated using realistic diffusion and functional MRI phantom data. It is shown that the proposed model recovers the maximum number of true connections, with fewest number of false connections when compared with the connectivity derived from a joint probabilistic model using the expectation-maximization (EM) algorithm presented in a prior work. We also apply the proposed method to data provided by the Human Connectome Project (HCP).

Normative brain size variation and brain shape diversity in humans.

PubMed

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

2018-06-15

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

Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

PubMed

Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

2010-05-17

The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.

Identification and classification of hubs in brain networks.

PubMed

Sporns, Olaf; Honey, Christopher J; Kötter, Rolf

2007-10-17

Brain regions in the mammalian cerebral cortex are linked by a complex network of fiber bundles. These inter-regional networks have previously been analyzed in terms of their node degree, structural motif, path length and clustering coefficient distributions. In this paper we focus on the identification and classification of hub regions, which are thought to play pivotal roles in the coordination of information flow. We identify hubs and characterize their network contributions by examining motif fingerprints and centrality indices for all regions within the cerebral cortices of both the cat and the macaque. Motif fingerprints capture the statistics of local connection patterns, while measures of centrality identify regions that lie on many of the shortest paths between parts of the network. Within both cat and macaque networks, we find that a combination of degree, motif participation, betweenness centrality and closeness centrality allows for reliable identification of hub regions, many of which have previously been functionally classified as polysensory or multimodal. We then classify hubs as either provincial (intra-cluster) hubs or connector (inter-cluster) hubs, and proceed to show that lesioning hubs of each type from the network produces opposite effects on the small-world index. Our study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles.

Gross Brain Morphology in Schizophrenia: A Regional Analysis of Traditional Diagnostic Subtypes.

ERIC Educational Resources Information Center

Raz, Sarah

1994-01-01

Categorized 56 patients with chronic schizophrenia into 2 groups based on traditional diagnostic subtypology. Compared groups on indices of cortical and subcortical cerebrospinal fluid (SCF) volume to explore whether more virulent nonparanoid disorder was linked to cortical/subcortical morphological brain abnormalities. Two groups differed…

Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

PubMed Central

Cooper, Nicole; Tompson, Steve; O’Donnell, Matthew Brook; Falk, Emily B.

2017-01-01

In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change. PMID:29057013

Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients.

PubMed

Ibrahim, El Chérif; Guillemot, Vincent; Comte, Magali; Tenenhaus, Arthur; Zendjidjian, Xavier Yves; Cancel, Aida; Belzeaux, Raoul; Sauvanaud, Florence; Blin, Olivier; Frouin, Vincent; Fakra, Eric

2017-09-07

Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia. SEARCHING FOR LINKS TO AID DIAGNOSIS: Researchers explore links between the expression of genes associated with schizophrenia in blood cells and variations in brain activity during emotion processing. El Chérif Ibrahim and Eric Fakra at Aix-Marseille Université, France, and colleagues have developed a method to relate the expression levels of 33 schizophrenia susceptibility genes in blood cells and functional magnetic resonance imaging (fMRI) data obtained as individuals carry out a task that triggers emotional responses. Although they found no significant differences in the expression of genes between the 26 patients with schizophrenia and 26 healthy controls they examined, variations in activity in the superior temporal gyrus were strongly linked to schizophrenia-associated gene expression and presence of disease. Similar analyses of larger data sets will shed further light on the relationship between peripheral molecular changes and disease-related behaviors and ultimately, aid the diagnosis of neuropsychiatric disease.

Regional expression of the MAPT gene is associated with loss of hubs in brain networks and cognitive impairment in Parkinson disease and progressive supranuclear palsy.

PubMed

Rittman, Timothy; Rubinov, Mikail; Vértes, Petra E; Patel, Ameera X; Ginestet, Cedric E; Ghosh, Boyd C P; Barker, Roger A; Spillantini, Maria Grazia; Bullmore, Edward T; Rowe, James B

2016-12-01

Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects (n = 128), we examined functional brain networks and measured the connection strength between 471 gray matter regions. We obtained MAPT and SNCA microarray expression data in healthy subjects from the Allen brain atlas. Regional connectivity varied according to the normal expression of MAPT. The regional expression of MAPT correlated with the proportionate loss of regional connectivity in Parkinson's disease. Executive cognition was impaired in proportion to the loss of hub connectivity. These effects were not seen with SNCA, suggesting that alpha-synuclein pathology is not mediated through global network properties. The results establish a link between regional MAPT expression and selective vulnerability of functional brain networks to neurodegeneration. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-06-13

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

Neural Mechanisms Linking Mild Traumatic Brain Injury and Anxiety States in an Animal Model

DTIC Science & Technology

2011-09-01

cells in each region were determined. In separate groups of rats, the effects of mTBI on anxiety-like behaviors, motor function, nociception, and...granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury. J Neurotrauma 22 :978-988...Furthermore, this research suggests that heightened fear and anxiety states following mild TBI may result from alterations to cell death and neuronal

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy.

PubMed

Youssofzadeh, Vahab; Agler, William; Tenney, Jeffrey R; Kadis, Darren S

2018-06-04

Absence seizures are thought to be linked to abnormal interplays between regions of a thalamocortical network. However, the complexity of this widespread network makes characterizing the functional interactions among various brain regions challenging. Using whole-brain functional connectivity and network analysis of magnetoencephalography (MEG) data, we explored pre-treatment brain hubs ("highly connected nodes") of patients aged 6 to 12 years with childhood absence epilepsy. We analyzed ictal MEG data of 74 seizures from 16 patients. We employed a time-domain beamformer technique to estimate MEG sources in broadband (1-40 Hz) where the greatest power changes between ictal and preictal periods were identified. A phase synchrony measure, phase locking value, and a graph theory metric, eigenvector centrality (EVC), were utilized to quantify voxel-level connectivity and network hubs of ictal > preictal periods, respectively. A volumetric atlas containing 116 regions of interests (ROIs) was utilized to summarize the network measures. ROIs with EVC (z-score) > 1.96 were reported as critical hubs. ROIs analysis revealed functional-anatomical hubs in a widespread network containing bilateral precuneus (right/left, z = 2.39, 2.18), left thalamus (z = 2.28), and three anterior cerebellar subunits of lobule "IV-V" (z = 3.9), vermis "IV-V" (z = 3.57), and lobule "III" (z = 2.03). Findings suggest that highly connected brain areas or hubs are present in focal cortical, subcortical, and cerebellar regions during absence seizures. Hubs in thalami, precuneus and cingulate cortex generally support a theory of rapidly engaging and bilaterally distributed networks of cortical and subcortical regions responsible for seizures generation, whereas hubs in anterior cerebellar regions may be linked to terminating motor automatisms frequently seen during typical absence seizures. Whole-brain network connectivity is a powerful analytic tool to reveal focal components of absence seizures in MEG. Our investigations can lead to a better understanding of the pathophysiology of CAE. Copyright © 2018 Elsevier B.V. All rights reserved.

Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.

PubMed

Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L; Martin, Nicholas G; Ho, Yvonne Y W; Malone, Stephen M; Zhang, Jian; Burwell, Scott J; Chorlian, David B; de Geus, Eco J C; Denys, Damiaan; Hansell, Narelle K; Hottenga, Jouke-Jan; McGue, Matt; van Beijsterveldt, Catharina E M; Jahanshad, Neda; Thompson, Paul M; Whelan, Christopher D; Medland, Sarah E; Porjesz, Bernice; Lacono, William G; Boomsma, Dorret I

2018-06-26

Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta 4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene-based analysis and brain-expression analyses. GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABA A interneuron activity and beta oscillations. Tissue-specific SNP-based imputation of gene-expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty-four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Optical imaging of the rat brain suggests a previously missing link between top-down and bottom-up nervous system function

PubMed Central

Greenfield, Susan A.; Badin, Antoine-Scott; Ferrati, Giovanni; Devonshire, Ian M.

2017-01-01

Abstract. Optical imaging with voltage-sensitive dyes enables the visualization of extensive yet highly transient coalitions of neurons (assemblies) operating throughout the brain on a subsecond time scale. We suggest that operating at the mesoscale level of brain organization, neuronal assemblies may provide a functional link between “bottom-up” cellular mechanisms and “top-down” cognitive ones within anatomically defined regions. We demonstrate in ex vivo rat brain slices how varying spatiotemporal dynamics of assemblies reveal differences not previously appreciated between: different stages of development in cortical versus subcortical brain areas, different sensory modalities (hearing versus vision), different classes of psychoactive drugs (anesthetics versus analgesics), different effects of anesthesia linked to hyperbaric conditions and, in vivo, depths of anesthesia. The strategy of voltage-sensitive dye imaging is therefore as powerful as it is versatile and as such can now be applied to the evaluation of neurochemical signaling systems and the screening of related new drugs, as well as to mathematical modeling and, eventually, even theories of consciousness. PMID:28573153

Optical imaging of the rat brain suggests a previously missing link between top-down and bottom-up nervous system function.

PubMed

Greenfield, Susan A; Badin, Antoine-Scott; Ferrati, Giovanni; Devonshire, Ian M

2017-07-01

Optical imaging with voltage-sensitive dyes enables the visualization of extensive yet highly transient coalitions of neurons (assemblies) operating throughout the brain on a subsecond time scale. We suggest that operating at the mesoscale level of brain organization, neuronal assemblies may provide a functional link between "bottom-up" cellular mechanisms and "top-down" cognitive ones within anatomically defined regions. We demonstrate in ex vivo rat brain slices how varying spatiotemporal dynamics of assemblies reveal differences not previously appreciated between: different stages of development in cortical versus subcortical brain areas, different sensory modalities (hearing versus vision), different classes of psychoactive drugs (anesthetics versus analgesics), different effects of anesthesia linked to hyperbaric conditions and, in vivo , depths of anesthesia. The strategy of voltage-sensitive dye imaging is therefore as powerful as it is versatile and as such can now be applied to the evaluation of neurochemical signaling systems and the screening of related new drugs, as well as to mathematical modeling and, eventually, even theories of consciousness.

Variations of response time in a selective attention task are linked to variations of functional connectivity in the attentional network.

PubMed

Prado, Jérôme; Carp, Joshua; Weissman, Daniel H

2011-01-01

Although variations of response time (RT) within a particular experimental condition are typically ignored, they may sometimes reflect meaningful changes in the efficiency of cognitive and neural processes. In the present study, we investigated whether trial-by-trial variations of response time (RT) in a cross-modal selective attention task were associated with variations of functional connectivity between brain regions that are thought to underlie attention. Sixteen healthy young adults performed an audiovisual selective attention task, which involved attending to a relevant visual letter while ignoring an irrelevant auditory letter, as we recorded their brain activity using functional magnetic resonance imaging (fMRI). In line with predictions, variations of RT were associated with variations of functional connectivity between the anterior cingulate cortex and various other brain regions that are posited to underlie attentional control, such as the right dorsolateral prefrontal cortex and bilateral regions of the posterior parietal cortex. They were also linked to variations of functional connectivity between anatomically early and anatomically late regions of the relevant-modality visual cortex whose communication is thought to be modulated by attentional control processes. By revealing that variations of RT in a selective attention task are linked to variations of functional connectivity in the attentional network, the present findings suggest that variations of attention may contribute to trial-by-trial fluctuations of behavioral performance. Copyright © 2010 Elsevier Inc. All rights reserved.

Brain Oscillatory Activity during Spatial Navigation: Theta and Gamma Activity Link Medial Temporal and Parietal Regions

ERIC Educational Resources Information Center

White, David J.; Congedo, Marco; Ciorciari, Joseph; Silberstein, Richard B.

2012-01-01

Brain oscillatory correlates of spatial navigation were investigated using blind source separation (BSS) and standardized low resolution electromagnetic tomography (sLORETA) analyses of 62-channel EEG recordings. Twenty-five participants were instructed to navigate to distinct landmark buildings in a previously learned virtual reality town…

Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

NASA Astrophysics Data System (ADS)

Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

2017-04-01

Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

Regional Blood-Brain Barrier Responses to Central Cholinergic Activity

DTIC Science & Technology

1989-07-30

i.e., oxotremorine, pilocarpine, carbachol , physostigmine [Olney et al., 1983]). These are some of the same regions affected by soman-induced...Diehl et al., 1984). Carbachol kindling also has been reported (Wasterlain, 1989), linking the cholinergic system to an increase in the sensitivity to

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Munro, Cynthia A; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K; Adams, Ashley V; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R; Pomper, Martin G

2015-02-01

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play. Copyright © 2014 Elsevier Inc. All rights reserved.

Correlation between pulmonary function and brain volume in healthy elderly subjects.

PubMed

Taki, Yasuyuki; Kinomura, Shigeo; Ebihara, Satoru; Thyreau, Benjamin; Sato, Kazunori; Goto, Ryoi; Kakizaki, Masako; Tsuji, Ichiro; Kawashima, Ryuta; Fukuda, Hiroshi

2013-06-01

Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Brain network disturbance related to posttraumatic stress and traumatic brain injury in veterans.

PubMed

Spielberg, Jeffrey M; McGlinchey, Regina E; Milberg, William P; Salat, David H

2015-08-01

Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI. Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus. Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI. Published by Elsevier Inc.

Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

NASA Astrophysics Data System (ADS)

Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

2017-10-01

Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

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

PubMed

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

2017-02-01

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

Different types of theta rhythmicity are induced by social and fearful stimuli in a network associated with social memory.

PubMed

Tendler, Alex; Wagner, Shlomo

2015-02-16

Rhythmic activity in the theta range is thought to promote neuronal communication between brain regions. In this study, we performed chronic telemetric recordings in socially behaving rats to monitor electrophysiological activity in limbic brain regions linked to social behavior. Social encounters were associated with increased rhythmicity in the high theta range (7-10 Hz) that was proportional to the stimulus degree of novelty. This modulation of theta rhythmicity, which was specific for social stimuli, appeared to reflect a brain-state of social arousal. In contrast, the same network responded to a fearful stimulus by enhancement of rhythmicity in the low theta range (3-7 Hz). Moreover, theta rhythmicity showed different pattern of coherence between the distinct brain regions in response to social and fearful stimuli. We suggest that the two types of stimuli induce distinct arousal states that elicit different patterns of theta rhythmicity, which cause the same brain areas to communicate in different modes.

Communicative versus strategic rationality: Habermas theory of communicative action and the social brain.

PubMed

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action.

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 representation of emotion regulation goals.

PubMed

Morawetz, Carmen; Bode, Stefan; Baudewig, Juergen; Jacobs, Arthur M; Heekeren, Hauke R

2016-02-01

The use of top-down cognitive control mechanisms to regulate emotional responses as circumstances change is critical for mental and physical health. Several theoretical models of emotion regulation have been postulated; it remains unclear, however, in which brain regions emotion regulation goals (e.g., the downregulation of fear) are represented. Here, we examined the neural mechanisms of regulating emotion using fMRI and identified brain regions representing reappraisal goals. Using a multimethodological analysis approach, combining standard activation-based and pattern-information analyses, we identified a distributed network of lateral frontal, temporal, and parietal regions implicated in reappraisal and within it, a core system that represents reappraisal goals in an abstract, stimulus-independent fashion. Within this core system, the neural pattern-separability in a subset of regions including the left inferior frontal gyrus, middle temporal gyrus, and inferior parietal lobe was related to the success in emotion regulation. Those brain regions might link the prefrontal control regions with the subcortical affective regions. Given the strong association of this subsystem with inner speech functions and semantic memory, we conclude that those cognitive mechanisms may be used for orchestrating emotion regulation. Hum Brain Mapp 37:600-620, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress-induced dendritic remodeling across OFC, BLA, and DHC. Together, these data suggest the potential for microglia-mediated sex differences in stress effects on neural structure, function, and behavior. PMID:29194444

Brain in situ hybridization maps as a source for reverse-engineering transcriptional regulatory networks: Alzheimer's disease insights

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

Acquaah-Mensah, George K.; Taylor, Ronald C.

Microarray data have been a valuable resource for identifying transcriptional regulatory relationships among genes. As an example, brain region-specific transcriptional regulatory events have the potential of providing etiological insights into Alzheimer Disease (AD). However, there is often a paucity of suitable brain-region specific expression data obtained via microarrays or other high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data sets (Jones et al., 2009) represent a potentially valuable alternative source of high-throughput brain region-specific gene expression data for such purposes. In this study, Allen BrainAtlasmouse ISH data in the hippocampal fields were extracted, focusing on 508 genesmore » relevant to neurodegeneration. Transcriptional regulatory networkswere learned using three high-performing network inference algorithms. Only 17% of regulatory edges from a network reverse-engineered based on brain region-specific ISH data were also found in a network constructed upon gene expression correlations inmousewhole brain microarrays, thus showing the specificity of gene expression within brain sub-regions. Furthermore, the ISH data-based networks were used to identify instructive transcriptional regulatory relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif, potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1, andSyn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and could be among links between dietary influences and genes in the AD etiology. Thus, this approach of harnessing brain region-specific ISH data represents a rare opportunity for gleaning unique etiological insights for diseases such as AD.« less

Task-Based Core-Periphery Organization of Human Brain Dynamics

PubMed Central

Bassett, Danielle S.; Wymbs, Nicholas F.; Rombach, M. Puck; Porter, Mason A.; Mucha, Peter J.; Grafton, Scott T.

2013-01-01

As a person learns a new skill, distinct synapses, brain regions, and circuits are engaged and change over time. In this paper, we develop methods to examine patterns of correlated activity across a large set of brain regions. Our goal is to identify properties that enable robust learning of a motor skill. We measure brain activity during motor sequencing and characterize network properties based on coherent activity between brain regions. Using recently developed algorithms to detect time-evolving communities, we find that the complex reconfiguration patterns of the brain's putative functional modules that control learning can be described parsimoniously by the combined presence of a relatively stiff temporal core that is composed primarily of sensorimotor and visual regions whose connectivity changes little in time and a flexible temporal periphery that is composed primarily of multimodal association regions whose connectivity changes frequently. The separation between temporal core and periphery changes over the course of training and, importantly, is a good predictor of individual differences in learning success. The core of dynamically stiff regions exhibits dense connectivity, which is consistent with notions of core-periphery organization established previously in social networks. Our results demonstrate that core-periphery organization provides an insightful way to understand how putative functional modules are linked. This, in turn, enables the prediction of fundamental human capacities, including the production of complex goal-directed behavior. PMID:24086116

Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease

PubMed Central

Mullins, Roger J.; Diehl, Thomas C.; Chia, Chee W.; Kapogiannis, Dimitrios

2017-01-01

Current hypotheses and theories regarding the pathogenesis of Alzheimer’s disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments. We present two promising biomarkers for brain IR in AD: insulin cascade mediators probed in extracellular vesicles (EVs) enriched for neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS) measures of brain glucose. As further evidence for a fundamental link between brain IR and AD, we provide a novel analysis demonstrating the close spatial correlation between brain expression of genes implicated in IR (using Allen Human Brain Atlas data) and tau and beta-amyloid pathologies. We proceed to propose the bold hypotheses that baseline differences in the metabolic reliance on glycolysis, and the expression of glucose transporters (GLUT) and insulin signaling genes determine the vulnerability of different brain regions to Tau and/or Amyloid beta (Aβ) pathology, and that IR is a critical link between these two pathologies that define AD. Lastly, we provide an overview of ongoing clinical trials that target IR as an angle to treat AD, and suggest how biomarkers may be used to evaluate treatment efficacy and target engagement. PMID:28515688

Functional connectivity associated with social networks in older adults: A resting-state fMRI study.

PubMed

Pillemer, Sarah; Holtzer, Roee; Blumen, Helena M

2017-06-01

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social networks using the Social Network Index (SNI) and resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data from 28 non-demented older adults were analyzed with independent components analyses. As expected, four established resting-state networks-previously linked to motor, vision, speech, and other language functions-correlated with the quality (SNI-1: total number of high-contact roles of a respondent) and quantity (SNI-2: total number of individuals in a respondent's social network) of social networks: a sensorimotor, a visual, a vestibular/insular, and a left frontoparietal network. Moreover, SNI-1 was associated with greater functional connectivity in the lateral prefrontal regions of the left frontoparietal network, while SNI-2 was associated with greater functional connectivity in the medial prefrontal regions of this network. Thus, lateral prefrontal regions may be particularly linked to the quality of social networks while medial prefrontal regions may be particularly linked to the quantity of social networks.

Morning nutrition and executive function processes in preadolescents: modulation of frontal event-related theta, beta and gamma EEG oscillations during a go/ no-go task

USDA-ARS?s Scientific Manuscript database

Executive functions (i.e., goal-directed behavior such as inhibition and flexibility of action) have been linked to frontal brain regions and to covariations in oscillatory brain activity, e.g., theta and gamma activity. We studied the effects of morning nutritional status on executive function rel...

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

PubMed

Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

2017-08-15

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous and Noninvasive Imaging of Cerebral Oxygen Metabolic Rate, Blood Flow and Oxygen Extraction Fraction in Stroke Mice

PubMed Central

Zhu, Xiao-Hong; Chen, James; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2012-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO2 and CBF. This study employed the recently developed in vivo 17O MR spectroscopic imaging to simultaneously assess CMRO2, CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of 17O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive 17O-MR approach for rapidly imaging CMRO2, CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO2 and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising 17O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This 17O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. PMID:23000789

Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice.

PubMed

Zhu, Xiao-Hong; Chen, James M; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2013-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO(2) and CBF. This study employed the recently developed in vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising (17)O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Excessive users of violent video games do not show emotional desensitization: an fMRI study.

PubMed

Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

2017-06-01

Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study.

PubMed

Schrepf, Andrew; Harper, Daniel E; Harte, Steven E; Wang, Heng; Ichesco, Eric; Hampson, Johnson P; Zubieta, Jon-Kar; Clauw, Daniel J; Harris, Richard E

2016-10-01

Endogenous opioid system dysfunction potentially contributes to chronic pain in fibromyalgia (FM), but it is unknown if this dysfunction is related to established neurobiological markers of hyperalgesia. We previously reported that µ-opioid receptor (MOR) availability was reduced in patients with FM as compared with healthy controls in several pain-processing brain regions. In the present study, we compared pain-evoked functional magnetic resonance imaging with endogenous MOR binding and clinical pain ratings in female opioid-naive patients with FM (n = 18) using whole-brain analyses and regions of interest from our previous research. Within antinociceptive brain regions, including the dorsolateral prefrontal cortex (r = 0.81, P < 0.001) and multiple regions of the anterior cingulate cortex (all r > 0.67; all P < 0.02), reduced MOR availability was associated with decreased pain-evoked neural activity. Additionally, reduced MOR availability was associated with lower brain activation in the nucleus accumbens (r = 0.47, P = 0.050). In many of these regions, pain-evoked activity and MOR binding potential were also associated with lower clinical affective pain ratings. These findings are the first to link endogenous opioid system tone to regional pain-evoked brain activity in a clinical pain population. Our data suggest that dysregulation of the endogenous opioid system in FM could lead to less excitation in antinociceptive brain regions by incoming noxious stimulation, resulting in the hyperalgesia and allodynia commonly observed in this population. We propose a conceptual model of affective pain dysregulation in FM.

Cortical and subcortical predictive dynamics and learning during perception, cognition, emotion and action

PubMed Central

Grossberg, Stephen

2009-01-01

An intimate link exists between the predictive and learning processes in the brain. Perceptual/cognitive and spatial/motor processes use complementary predictive mechanisms to learn, recognize, attend and plan about objects in the world, determine their current value, and act upon them. Recent neural models clarify these mechanisms and how they interact in cortical and subcortical brain regions. The present paper reviews and synthesizes data and models of these processes, and outlines a unified theory of predictive brain processing. PMID:19528003

A common brain network links development, aging, and vulnerability to disease.

PubMed

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Perspectives from the symposium: The role of nutrition in infant and toddler brain and behavioral development.

PubMed

Rosales, Francisco J; Zeisel, Steven H

2008-06-01

This symposium examined current trends in neuroscience and developmental psychology as they apply to assessing the effects of nutrients on brain and behavioral development of 0-6-year-olds. Although the spectrum of nutrients with brain effects has not changed much in the last 25 years, there has been an explosion in new knowledge about the genetics, structure and function of the brain. This has helped to link the brain mechanistic pathway by which these nutrients act with cognitive functions. A clear example of this is linking of brain structural changes due to hypoglycemia versus hyperglycemia with cognitive functions by using magnetic resonance imaging (MRI) to assess changes in brain-region volumes in combination with cognitive test of intelligence, memory and processing speed. Another example is the use of event-related potential (ERP) studies to show that infants of diabetic mothers have impairments in memory from birth through 8 months of age that are consistent with alterations in mechanistic pathways of memory observed in animal models of perinatal iron deficiency. However, gaps remain in the understanding of how nutrients and neurotrophic factors interact with each other in optimizing brain development and function.

Linking brain-wide multivoxel activation patterns to behaviour: Examples from language and math.

PubMed

Raizada, Rajeev D S; Tsao, Feng-Ming; Liu, Huei-Mei; Holloway, Ian D; Ansari, Daniel; Kuhl, Patricia K

2010-05-15

A key goal of cognitive neuroscience is to find simple and direct connections between brain and behaviour. However, fMRI analysis typically involves choices between many possible options, with each choice potentially biasing any brain-behaviour correlations that emerge. Standard methods of fMRI analysis assess each voxel individually, but then face the problem of selection bias when combining those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI analysis methods use classifiers to analyse multiple voxels together, but can also introduce selection bias via data-reduction steps as feature selection of voxels, pre-selecting activated regions, or principal components analysis. We show here that strong brain-behaviour links can be revealed without any voxel selection or data reduction, using just plain linear regression as a classifier applied to the whole brain at once, i.e. treating each entire brain volume as a single multi-voxel pattern. The brain-behaviour correlations emerged despite the fact that the classifier was not provided with any information at all about subjects' behaviour, but instead was given only the neural data and its condition-labels. Surprisingly, more powerful classifiers such as a linear SVM and regularised logistic regression produce very similar results. We discuss some possible reasons why the very simple brain-wide linear regression model is able to find correlations with behaviour that are as strong as those obtained on the one hand from a specific ROI and on the other hand from more complex classifiers. In a manner which is unencumbered by arbitrary choices, our approach offers a method for investigating connections between brain and behaviour which is simple, rigorous and direct. Copyright (c) 2010 Elsevier Inc. All rights reserved.

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

PubMed Central

Sripada, Rebecca K; Marx, Christine E; King, Anthony P; Rajaram, Nirmala; Garfinkel, Sarah N; Abelson, James L; Liberzon, Israel

2013-01-01

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects. PMID:23552182

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

Meta-connectomics: human brain network and connectivity meta-analyses.

PubMed

Crossley, N A; Fox, P T; Bullmore, E T

2016-04-01

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Neural predictors of chocolate intake following chocolate exposure.

PubMed

Frankort, Astrid; Roefs, Anne; Siep, Nicolette; Roebroeck, Alard; Havermans, Remco; Jansen, Anita

2015-04-01

Previous studies have shown that one's brain response to high-calorie food cues can predict long-term weight gain or weight loss. The neural correlates that predict food intake in the short term have, however, hardly been investigated. This study examined which brain regions' activation predicts chocolate intake after participants had been either exposed to real chocolate or to control stimuli during approximately one hour, with interruptions for fMRI measurements. Further we investigated whether the variance in chocolate intake could be better explained by activated brain regions than by self-reported craving. In total, five brain regions correlated with subsequent chocolate intake. The activation of two reward regions (the right caudate and the left frontopolar cortex) correlated positively with intake in the exposure group. The activation of two regions associated with cognitive control (the left dorsolateral and left mid-dorsolateral PFC) correlated negatively with intake in the control group. When the regression analysis was conducted with the exposure and the control group together, an additional region's activation (the right anterior PFC) correlated positively with chocolate intake. In all analyses, the intake variance explained by neural correlates was above and beyond the variance explained by self-reported craving. These results are in line with neuroimaging research showing that brain responses are a better predictor of subsequent intake than self-reported craving. Therefore, our findings might provide for a missing link by associating brain activation, previously shown to predict weight change, with short-term intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

Communicative versus Strategic Rationality: Habermas Theory of Communicative Action and the Social Brain

PubMed Central

Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael; Denke, Claudia

2013-01-01

In the philosophical theory of communicative action, rationality refers to interpersonal communication rather than to a knowing subject. Thus, a social view of rationality is suggested. The theory differentiates between two kinds of rationality, the emancipative communicative and the strategic or instrumental reasoning. Using experimental designs in an fMRI setting, recent studies explored similar questions of reasoning in the social world and linked them with a neural network including prefrontal and parietal brain regions. Here, we employed an fMRI approach to highlight brain areas associated with strategic and communicative reasoning according to the theory of communicative action. Participants were asked to assess different social scenarios with respect to communicative or strategic rationality. We found a network of brain areas including temporal pole, precuneus, and STS more activated when participants performed communicative reasoning compared with strategic thinking and a control condition. These brain regions have been previously linked to moral sensitivity. In contrast, strategic rationality compared with communicative reasoning and control was associated with less activation in areas known to be related to moral sensitivity, emotional processing, and language control. The results suggest that strategic reasoning is associated with reduced social and emotional cognitions and may use different language related networks. Thus, the results demonstrate experimental support for the assumptions of the theory of communicative action. PMID:23734238

A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion.

PubMed

Post, Andrew; Oeur, Anna; Walsh, Evan; Hoshizaki, Blaine; Gilchrist, Michael D

2014-01-01

American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.

Anatomical and functional assemblies of brain BOLD oscillations

PubMed Central

Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

2011-01-01

Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

Assessment of brain activity during voluntary anal sphincter contraction: Comparative study in women with and without fecal incontinence.

PubMed

Parés, D; Martínez-Vilalta, M; Ortiz, H; Soriano-Mas, C; Maestre-Gonzalez, Y; Pujol, J; Grande, L

2018-04-14

Voluntary anal sphincter function is driven by an extended network of brain structures, most of which are still unknown. Disturbances in this function may cause fecal incontinence. The aim of this study was to characterize the cerebral areas involved in voluntary contraction of the anorectal sphincter in healthy women and in a group of patients with fecal incontinence by using a standardized functional magnetic resonance imaging (fMRI) protocol. This comparative study included 12 healthy women (mean age 53.17 ± 4.93 years) and 12 women with fecal incontinence (56.25 ± 6.94 years). An MRI-compatible anal manometer was used to register voluntary external anal sphincter contraction. During brain fMRI imaging, participants were cued to perform 10-s series of self-paced anal sphincter contractions at an approximate rate of 1 Hz. Brain structures linked to anal sphincter contractions were mapped and the findings were compared between the 2 study groups. There were no differences in the evoked brain activity between the 2 groups. In healthy women, group fMRI analysis revealed significant activations in medial primary motor cortices, supplementary motor area, bilateral putamen, and cerebellum, as well as in the supramarginal gyrus and visual areas. In patients with fecal incontinence, the activation pattern involved similar regions without significant differences with healthy women. This brain fMRI-anorectal protocol was able to map the brain regions linked to voluntary anal sphincter function in healthy and women with fecal incontinence. © 2018 John Wiley & Sons Ltd.

Attachment Security in Infancy: A Preliminary Study of Prospective Links to Brain Morphometry in Late Childhood

PubMed Central

Leblanc, Élizabel; Dégeilh, Fanny; Daneault, Véronique; Beauchamp, Miriam H.; Bernier, Annie

2017-01-01

A large body of longitudinal research provides compelling evidence for the critical role of early attachment relationships in children’s social, emotional, and cognitive development. It is expected that parent–child attachment relationships may also impact children’s brain development, however, studies linking normative caregiving experiences and brain structure are scarce. To our knowledge, no study has yet examined the associations between the quality of parent–infant attachment relationships and brain morphology during childhood. The aim of this preliminary study was to investigate the prospective links between mother–infant attachment security and whole-brain gray matter (GM) volume and thickness in late childhood. Attachment security toward the mother was assessed in 33 children when they were 15 months old. These children were then invited to undergo structural magnetic resonance imaging at 10–11 years of age. Results indicated that children more securely attached to their mother in infancy had larger GM volumes in the superior temporal sulcus and gyrus, temporo-parietal junction, and precentral gyrus in late childhood. No associations between attachment security and cortical thickness were found. If replicated, these results would suggest that a secure attachment relationship and its main features (e.g., adequate dyadic emotion regulation, competent exploration) may influence GM volume in brain regions involved in social, cognitive, and emotional functioning through experience-dependent processes. PMID:29312029

Controlling self-sustained spiking activity by adding or removing one network link

NASA Astrophysics Data System (ADS)

Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

2013-06-01

Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

Latent Variable Modeling of Brain Gray Matter Volume and Psychopathy in Incarcerated Offenders

PubMed Central

Baskin-Sommers, Arielle R.; Neumann, Craig S.; Cope, Lora M.; Kiehl, Kent A.

2016-01-01

Advanced statistical modeling has become a prominent feature in psychological science and can be a useful approach for representing the neural architecture linked to psychopathology. Psychopathy, a disorder characterized by dysfunction in interpersonal-affective and impulsive-antisocial domains, is associated with widespread neural abnormalities. Several imaging studies suggest that underlying structural deficits in paralimbic regions are associated with psychopathy. While these studies are useful, they make assumptions about the organization of the brain and its relevance to individuals displaying psychopathic features. Capitalizing on statistical modeling, the present study (N=254) used latent variable methods to examine the structure of gray matter volume in male offenders, and assessed the latent relations between psychopathy and gray matter factors reflecting paralimbic and non-paralimbic regions. Results revealed good fit for a four-factor gray matter paralimbic model and these first-order factors were accounted for by a super-ordinate paralimbic ‘system’ factor. Moreover, a super-ordinate psychopathy factor significantly predicted the paralimbic, but not the non-paralimbic factor. The latent variable paralimbic model, specifically linked with psychopathy, goes beyond understanding of single brain regions within the system and provides evidence for psychopathy-related gray matter volume reductions in the paralimbic system as a whole. PMID:27269123

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

PubMed

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

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

The Association between Lifelong Greenspace Exposure and 3-Dimensional Brain Magnetic Resonance Imaging in Barcelona Schoolchildren.

PubMed

Dadvand, Payam; Pujol, Jesus; Macià, Dídac; Martínez-Vilavella, Gerard; Blanco-Hinojo, Laura; Mortamais, Marion; Alvarez-Pedrerol, Mar; Fenoll, Raquel; Esnaola, Mikel; Dalmau-Bueno, Albert; López-Vicente, Mónica; Basagaña, Xavier; Jerrett, Michael; Nieuwenhuijsen, Mark J; Sunyer, Jordi

2018-02-23

Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure. We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school. We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across 100-m buffers around all residential addresses since birth to estimate each participant's lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory ( d' from computerized n -back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores. Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness. Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876.

Synthetic event-related potentials: a computational bridge between neurolinguistic models and experiments.

PubMed

Barrès, Victor; Simons, Arthur; Arbib, Michael

2013-01-01

Our previous work developed Synthetic Brain Imaging to link neural and schema network models of cognition and behavior to PET and fMRI studies of brain function. We here extend this approach to Synthetic Event-Related Potentials (Synthetic ERP). Although the method is of general applicability, we focus on ERP correlates of language processing in the human brain. The method has two components: Phase 1: To generate cortical electro-magnetic source activity from neural or schema network models; and Phase 2: To generate known neurolinguistic ERP data (ERP scalp voltage topographies and waveforms) from putative cortical source distributions and activities within a realistic anatomical model of the human brain and head. To illustrate the challenges of Phase 2 of the methodology, spatiotemporal information from Friederici's 2002 model of auditory language comprehension was used to define cortical regions and time courses of activation for implementation within a forward model of ERP data. The cortical regions from the 2002 model were modeled using atlas-based masks overlaid on the MNI high definition single subject cortical mesh. The electromagnetic contribution of each region was modeled using current dipoles whose position and orientation were constrained by the cortical geometry. In linking neural network computation via EEG forward modeling to empirical results in neurolinguistics, we emphasize the need for neural network models to link their architecture to geometrically sound models of the cortical surface, and the need for conceptual models to refine and adopt brain-atlas based approaches to allow precise brain anchoring of their modules. The detailed analysis of Phase 2 sets the stage for a brief introduction to Phase 1 of the program, including the case for a schema-theoretic approach to language production and perception presented in detail elsewhere. Unlike Dynamic Causal Modeling (DCM) and Bojak's mean field model, Synthetic ERP builds on models of networks that mediate the relation between the brain's inputs, outputs, and internal states in executing a specific task. The neural networks used for Synthetic ERP must include neuroanatomically realistic placement and orientation of the cortical pyramidal neurons. These constraints pose exciting challenges for future work in neural network modeling that is applicable to systems and cognitive neuroscience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Measuring Brain Connectivity: Diffusion Tensor Imaging Validates Resting State Temporal Correlations

PubMed Central

Skudlarski, Pawel; Jagannathan, Kanchana; Calhoun, Vince D.; Hampson, Michelle; Skudlarska, Beata A.; Pearlson, Godfrey

2015-01-01

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions. PMID:18771736

Measuring brain connectivity: diffusion tensor imaging validates resting state temporal correlations.

PubMed

Skudlarski, Pawel; Jagannathan, Kanchana; Calhoun, Vince D; Hampson, Michelle; Skudlarska, Beata A; Pearlson, Godfrey

2008-11-15

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions.

Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.

PubMed

Harnett, Erica L; Dickinson, Michelle A; Smith, Graeme N

2007-08-01

This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05). A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.

Pathological Laughing: Brain SPECT Findings.

PubMed

Morland, David; Wolff, Valérie; Blondet, Cyrille; Marescaux, Christian; Namer, Izzie Jacques

2015-09-01

We present the case of a 40-year-old man consulting for uncontrollable episodes of laughing related to emotional lability and not systematically linked to feelings of happiness. Seven months earlier he had presented a pontine ischemic stroke related to an occlusion of the basilar and left vertebral arteries. No epileptic activity or new MRI brain lesions were found. Brain perfusion SPECT performed showed marked hypoperfusion in the right frontal inferior and temporoinsular regions, suggesting a diaschisis phenomenon caused by pontine lesions and highlighted laughing regulation pathways. The patient was successfully treated with a serotonergic reuptake inhibitor, fluoxetine.

Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography.

PubMed

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

2017-12-01

The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Learning Temporal Statistics for Sensory Predictions in Aging.

PubMed

Luft, Caroline Di Bernardi; Baker, Rosalind; Goldstone, Aimee; Zhang, Yang; Kourtzi, Zoe

2016-03-01

Predicting future events based on previous knowledge about the environment is critical for successful everyday interactions. Here, we ask which brain regions support our ability to predict the future based on implicit knowledge about the past in young and older age. Combining behavioral and fMRI measurements, we test whether training on structured temporal sequences improves the ability to predict upcoming sensory events; we then compare brain regions involved in learning predictive structures between young and older adults. Our behavioral results demonstrate that exposure to temporal sequences without feedback facilitates the ability of young and older adults to predict the orientation of an upcoming stimulus. Our fMRI results provide evidence for the involvement of corticostriatal regions in learning predictive structures in both young and older learners. In particular, we showed learning-dependent fMRI responses for structured sequences in frontoparietal regions and the striatum (putamen) for young adults. However, for older adults, learning-dependent activations were observed mainly in subcortical (putamen, thalamus) regions but were weaker in frontoparietal regions. Significant correlations of learning-dependent behavioral and fMRI changes in these regions suggest a strong link between brain activations and behavioral improvement rather than general overactivation. Thus, our findings suggest that predicting future events based on knowledge of temporal statistics engages brain regions involved in implicit learning in both young and older adults.

New understanding of adolescent brain development: relevance to transitional healthcare for young people with long term conditions.

PubMed

Colver, Allan; Longwell, Sarah

2013-11-01

Whether or not adolescence should be treated as a special period, there is now no doubt that the brain changes much during adolescence. From an evolutionary perspective, the idea of an under developed brain which is not fit for purpose until adulthood is illogical. Rather, the adolescent brain is likely to support the challenges specific to that period of life. New imaging techniques show striking changes in white and grey matter between 11 and 25 years of age, with increased connectivity between brain regions, and increased dopaminergic activity in the pre-frontal cortices, striatum and limbic system and the pathways linking them. The brain is dynamic, with some areas developing faster and becoming more dominant until other areas catch up. Plausible mechanisms link these changes to cognitive and behavioural features of adolescence. The changing brain may lead to abrupt behavioural change with attendant risks, but such a brain is flexible and can respond quickly and imaginatively. Society allows adolescent exuberance and creativity to be bounded and explored in relative safety. In healthcare settings these changes are especially relevant to young people with long term conditions as they move to young adult life; such young people need to learn to manage their health conditions with the support of their healthcare providers.

Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction

PubMed Central

Wang, Danhong; Buckner, Randy L.

2014-01-01

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

Dissociable Effects on Birdsong of Androgen Signaling in Cortex-Like Brain Regions of Canaries

PubMed Central

2017-01-01

The neural basis of how learned vocalizations change during development and in adulthood represents a major challenge facing cognitive neuroscience. This plasticity in the degree to which learned vocalizations can change in both humans and songbirds is linked to the actions of sex steroid hormones during ontogeny but also in adulthood in the context of seasonal changes in birdsong. We investigated the role of steroid hormone signaling in the brain on distinct features of birdsong using adult male canaries (Serinus canaria), which show extensive seasonal vocal plasticity as adults. Specifically, we bilaterally implanted the potent androgen receptor antagonist flutamide in two key brain regions that control birdsong. We show that androgen signaling in the motor cortical-like brain region, the robust nucleus of the arcopallium (RA), controls syllable and trill bandwidth stereotypy, while not significantly affecting higher order features of song such syllable-type usage (i.e., how many times each syllable type is used) or syllable sequences. In contrast, androgen signaling in the premotor cortical-like brain region, HVC (proper name), controls song variability by increasing the variability of syllable-type usage and syllable sequences, while having no effect on syllable or trill bandwidth stereotypy. Other aspects of song, such as the duration of trills and the number of syllables per song, were also differentially affected by androgen signaling in HVC versus RA. These results implicate androgens in regulating distinct features of complex motor output in a precise and nonredundant manner. SIGNIFICANCE STATEMENT Vocal plasticity is linked to the actions of sex steroid hormones, but the precise mechanisms are unclear. We investigated this question in adult male canaries (Serinus canaria), which show extensive vocal plasticity throughout their life. We show that androgens in two cortex-like vocal control brain regions regulate distinct aspects of vocal plasticity. For example, in HVC (proper name), androgens regulate variability in syntax but not phonology, whereas androgens in the robust nucleus of the arcopallium (RA) regulate variability in phonology but not syntax. Temporal aspects of song were also differentially affected by androgen signaling in HVC versus RA. Thus, androgen signaling may reduce vocal plasticity by acting in a nonredundant and precise manner in the brain. PMID:28821656

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

PubMed

Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

2016-01-01

A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

PubMed

Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

2014-11-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

PubMed Central

Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

2014-01-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving.

PubMed

Garcia, Javier O; Brooks, Justin; Kerick, Scott; Johnson, Tony; Mullen, Tim R; Vettel, Jean M

2017-04-15

Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2-3Hz; theta: 4-7Hz; alpha: 8-12Hz; beta: 13-25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band. Published by Elsevier Inc.

Visual hallucinations of autobiographic memory and asomatognosia: a case of epilepsy due to brain cysticercosis.

PubMed

Orjuela-Rojas, Juan Manuel; Ramírez-Bermúdez, Jesús; Martínez-Juárez, Iris E; Kerik, Nora Estela; Diaz Meneses, Iván; Pérez-Gay, Fernanda Juárez

2015-01-01

The current study describes the case of a woman with symptomatic epilepsy due to brain cysticercosis acquired during childhood. During her adolescence, she developed seizures characterized by metamorphopsia, hallucinations of autobiographic memory and, finally, asomatognosia. Magnetic brain imaging showed a calcified lesion in the right occipitotemporal cortex, and positron emission tomography imaging confirmed the presence of interictal hypometabolism in two regions: the right parietal cortex and the right lateral and posterior temporal cortex. We discuss the link between these brain areas and the symptoms described under the concepts of epileptogenic lesion, epileptogenic zone, functional deficit zone, and symptomatogenic zone.

Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington's disease.

PubMed

McColgan, Peter; Seunarine, Kiran K; Razi, Adeel; Cole, James H; Gregory, Sarah; Durr, Alexandra; Roos, Raymund A C; Stout, Julie C; Landwehrmeyer, Bernhard; Scahill, Rachael I; Clark, Chris A; Rees, Geraint; Tabrizi, Sarah J

2015-11-01

Huntington's disease can be predicted many years before symptom onset, and thus makes an ideal model for studying the earliest mechanisms of neurodegeneration. Diffuse patterns of structural connectivity loss occur in the basal ganglia and cortex early in the disease. However, the organizational principles that underlie these changes are unclear. By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level. The 'rich club' is a pattern of organization established in healthy human brains, where specific hub 'rich club' brain regions are more highly connected to each other than other brain regions. We hypothesized that selective loss of rich club connectivity might represent an organizing principle underlying the distributed pattern of structural connectivity loss seen in Huntington's disease. To test this hypothesis we performed diffusion tractography and graph theoretical analysis in a pseudo-longitudinal study of 50 premanifest and 38 manifest Huntington's disease participants compared with 47 healthy controls. Consistent with our hypothesis we found that structural connectivity loss selectively affected rich club brain regions in premanifest and manifest Huntington's disease participants compared with controls. We found progressive network changes across controls, premanifest Huntington's disease and manifest Huntington's disease characterized by increased network segregation in the premanifest stage and loss of network integration in manifest disease. These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance. We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions. This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions. Our findings highlight the role of the rich club as a substrate for the structural connectivity loss seen in Huntington's disease and have broader implications for understanding the connection between molecular and systems level pathology in neurodegenerative disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Extraversion and neuroticism relate to topological properties of resting-state brain networks.

PubMed

Gao, Qing; Xu, Qiang; Duan, Xujun; Liao, Wei; Ding, Jurong; Zhang, Zhiqiang; Li, Yuan; Lu, Guangming; Chen, Huafu

2013-01-01

With the advent and development of modern neuroimaging techniques, there is an increasing interest in linking extraversion and neuroticism to anatomical and functional brain markers. Here, we aimed to test the theoretically derived biological personality model as proposed by Eysenck using graph theoretical analyses. Specifically, the association between the topological organization of whole-brain functional networks and extraversion/neuroticism was explored. To construct functional brain networks, functional connectivity among 90 brain regions was measured by temporal correlation using resting-state functional magnetic resonance imaging (fMRI) data of 71 healthy subjects. Graph theoretical analysis revealed a positive association of extraversion scores and normalized clustering coefficient values. These results suggested a more clustered configuration in brain networks of individuals high in extraversion, which could imply a higher arousal threshold and higher levels of arousal tolerance in the cortex of extraverts. On a local network level, we observed that a specific nodal measure, i.e., betweenness centrality (BC), was positively associated with neuroticism scores in the right precentral gyrus (PreCG), right caudate nucleus, right olfactory cortex, and bilateral amygdala. For individuals high in neuroticism, these results suggested a more frequent participation of these specific regions in information transition within the brain network and, in turn, may partly explain greater regional activation levels and lower arousal thresholds in these regions. In contrast, extraversion scores were positively correlated with BC in the right insula, while negatively correlated with BC in the bilateral middle temporal gyrus (MTG), indicating that the relationship between extraversion and regional arousal is not as simple as proposed by Eysenck.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents

PubMed Central

Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A.; Santoro, Nicola; Savoye, Mary; Duran, Elvira J.; Pierpont, Bridget; Cline, Gary; Constable, R. Todd; Sherwin, Robert S.

2016-01-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. PMID:27207544

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

PubMed

Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

2016-01-01

Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

Neural Mechanisms Linking Mild Traumatic Brain Injury and Anxiety States in an Animal Model

DTIC Science & Technology

2012-03-01

IGF-1R (Madathil et al., 2010, Rubovitch et al., 2010) to decrease 22 programmed cell death in these sub regions of the amygdala. Thus, whether... corticosterone in the rat medial hypothalamus potentiates D- fenfluramine-induced elevations of extracellular 5- HT concentrations. Hormones and Behavior. 56...in the Appendix). Brains were sectioned and stained to identify neurons for neuronal cell counts, and also stained using the TUNEL method to

Differential investment in visual and olfactory brain areas reflects behavioural choices in hawk moths

PubMed Central

Stöckl, Anna; Heinze, Stanley; Charalabidis, Alice; el Jundi, Basil; Warrant, Eric; Kelber, Almut

2016-01-01

Nervous tissue is one of the most metabolically expensive animal tissues, thus evolutionary investments that result in enlarged brain regions should also result in improved behavioural performance. Indeed, large-scale comparative studies in vertebrates and invertebrates have successfully linked differences in brain anatomy to differences in ecology and behaviour, but their precision can be limited by the detail of the anatomical measurements, or by only measuring behaviour indirectly. Therefore, detailed case studies are valuable complements to these investigations, and have provided important evidence linking brain structure to function in a range of higher-order behavioural traits, such as foraging experience or aggressive behaviour. Here, we show that differences in the size of both lower and higher-order sensory brain areas reflect differences in the relative importance of these senses in the foraging choices of hawk moths, as suggested by previous anatomical work in Lepidopterans. To this end we combined anatomical and behavioural quantifications of the relative importance of vision and olfaction in two closely related hawk moth species. We conclude that differences in sensory brain volume in these hawk moths can indeed be interpreted as differences in the importance of these senses for the animal’s behaviour. PMID:27185464

The independent influences of age and education on functional brain networks and cognition in healthy older adults.

PubMed

Perry, Alistair; Wen, Wei; Kochan, Nicole A; Thalamuthu, Anbupalam; Sachdev, Perminder S; Breakspear, Michael

2017-10-01

Healthy aging is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during aging in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identified three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively normal elders. The first mode (P = 0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode (P = 0.012), characterized by the involvement of key hub regions. A third mode (P = 0.041) captures weak, residual brain-behavior relations. Our findings suggest that circuits supporting lower level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks-suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with aging. This has important implications in understanding the contribution of education to cognitive reserve during healthy aging. Hum Brain Mapp 38:5094-5114, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

High-cost, high-capacity backbone for global brain communication.

PubMed

van den Heuvel, Martijn P; Kahn, René S; Goñi, Joaquín; Sporns, Olaf

2012-07-10

Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.

Transcription map of Xq27: candidates for several X-linked diseases.

PubMed

Zucchi, I; Jones, J; Affer, M; Montagna, C; Redolfi, E; Susani, L; Vezzoni, P; Parvari, R; Schlessinger, D; Whyte, M P; Mumm, S

1999-04-15

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. Copyright 1999 Academic Press.

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

Quantitative prediction of perceptual decisions during near-threshold fear detection

NASA Astrophysics Data System (ADS)

Pessoa, Luiz; Padmala, Srikanth

2005-04-01

A fundamental goal of cognitive neuroscience is to explain how mental decisions originate from basic neural mechanisms. The goal of the present study was to investigate the neural correlates of perceptual decisions in the context of emotional perception. To probe this question, we investigated how fluctuations in functional MRI (fMRI) signals were correlated with behavioral choice during a near-threshold fear detection task. fMRI signals predicted behavioral choice independently of stimulus properties and task accuracy in a network of brain regions linked to emotional processing: posterior cingulate cortex, medial prefrontal cortex, right inferior frontal gyrus, and left insula. We quantified the link between fMRI signals and behavioral choice in a whole-brain analysis by determining choice probabilities by means of signal-detection theory methods. Our results demonstrate that voxel-wise fMRI signals can reliably predict behavioral choice in a quantitative fashion (choice probabilities ranged from 0.63 to 0.78) at levels comparable to neuronal data. We suggest that the conscious decision that a fearful face has been seen is represented across a network of interconnected brain regions that prepare the organism to appropriately handle emotionally challenging stimuli and that regulate the associated emotional response. decision making | emotion | functional MRI

Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

PubMed Central

Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

2014-01-01

When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

Creativity and borderline personality disorder: evidence from a voxel-based morphometry study.

PubMed

Leutgeb, Verena; Ille, Rottraut; Wabnegger, Albert; Schienle, Anne; Schöggl, Helmut; Weber, Bernhard; Papousek, Ilona; Weiss, Elisabeth M; Fink, Andreas

2016-05-01

Throughout the history, various examples of eminent creative people suffering from mental disorders along with some empirical research reports strengthened the idea of a potential link between creativity and psychopathology. This study investigated different facets of psychometrically determined creativity in 20 females diagnosed with borderline personality disorder (BPD) relative to 19 healthy female controls. In addition, group differences in grey matter (GM) were examined. Behavioural findings revealed no significant differences between the BPD group and healthy controls with respect to verbal and figural-graphic creative task performance and creativity-related personality characteristics. Whole-brain voxel-based morphometry analyses revealed a distinct pattern of GM reductions in the BPD group (relative to controls) in a network of brain regions closely associated with various cognitive and emotional functions (including the bilateral orbital inferior frontal gyri and the left superior temporal gyrus), partly overlapping with creativity-related brain regions. Correlation analyses moreover revealed that in the BPD group GM reductions in the orbital parts of the inferior and middle frontal gyri were associated with lower levels of creativity. This study provides no indications in favour of the putative link between creativity and psychopathology, as sometimes reported in the literature.

The experience of beauty derived from sorrow.

PubMed

Ishizu, Tomohiro; Zeki, Semir

2017-08-01

We studied the neural mechanisms that are engaged during the experience of beauty derived from sorrow and from joy, two experiences that share a common denominator (beauty) but are linked to opposite emotional valences. Twenty subjects viewed and rerated, in a functional magnetic resonance imaging scanner, 120 images which each had classified into the following four categories: beautiful and sad; beautiful and joyful; neutral; ugly. The medial orbito-frontal cortex (mOFC) was active during the experience of both types of beauty. Otherwise, the two experiences engaged different parts of the brain: joyful beauty engaged areas linked to positive emotions while sorrowful beauty engaged areas linked to negative experiences. Separate regions of the cerebellum were engaged during experience of the two conditions. A functional connectivity analysis indicated that the activity within the mOFC was modulated by the supplementary motor area/middle cingulate cortex, known to be engaged during empathetic experiences provoked by other peoples' sadness. Hum Brain Mapp 38:4185-4200, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The neural basis of responsibility attribution in decision-making.

PubMed

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

The Neural Basis of Responsibility Attribution in Decision-Making

PubMed Central

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID:24224053

Multi-scale radiomic analysis of sub-cortical regions in MRI related to autism, gender and age

NASA Astrophysics Data System (ADS)

Chaddad, Ahmad; Desrosiers, Christian; Toews, Matthew

2017-03-01

We propose using multi-scale image textures to investigate links between neuroanatomical regions and clinical variables in MRI. Texture features are derived at multiple scales of resolution based on the Laplacian-of-Gaussian (LoG) filter. Three quantifier functions (Average, Standard Deviation and Entropy) are used to summarize texture statistics within standard, automatically segmented neuroanatomical regions. Significance tests are performed to identify regional texture differences between ASD vs. TDC and male vs. female groups, as well as correlations with age (corrected p < 0.05). The open-access brain imaging data exchange (ABIDE) brain MRI dataset is used to evaluate texture features derived from 31 brain regions from 1112 subjects including 573 typically developing control (TDC, 99 females, 474 males) and 539 Autism spectrum disorder (ASD, 65 female and 474 male) subjects. Statistically significant texture differences between ASD vs. TDC groups are identified asymmetrically in the right hippocampus, left choroid-plexus and corpus callosum (CC), and symmetrically in the cerebellar white matter. Sex-related texture differences in TDC subjects are found in primarily in the left amygdala, left cerebellar white matter, and brain stem. Correlations between age and texture in TDC subjects are found in the thalamus-proper, caudate and pallidum, most exhibiting bilateral symmetry.

Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress.

PubMed

Chen, Yu-Chen; Chen, Guang-Di; Auerbach, Benjamin D; Manohar, Senthilvelan; Radziwon, Kelly; Salvi, Richard

2017-06-01

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Varieties of semantic cognition revealed through simultaneous decomposition of intrinsic brain connectivity and behaviour.

PubMed

Vatansever, Deniz; Bzdok, Danilo; Wang, Hao-Ting; Mollo, Giovanna; Sormaz, Mladen; Murphy, Charlotte; Karapanagiotidis, Theodoros; Smallwood, Jonathan; Jefferies, Elizabeth

2017-09-01

Contemporary theories assume that semantic cognition emerges from a neural architecture in which different component processes are combined to produce aspects of conceptual thought and behaviour. In addition to the state-level, momentary variation in brain connectivity, individuals may also differ in their propensity to generate particular configurations of such components, and these trait-level differences may relate to individual differences in semantic cognition. We tested this view by exploring how variation in intrinsic brain functional connectivity between semantic nodes in fMRI was related to performance on a battery of semantic tasks in 154 healthy participants. Through simultaneous decomposition of brain functional connectivity and semantic task performance, we identified distinct components of semantic cognition at rest. In a subsequent validation step, these data-driven components demonstrated explanatory power for neural responses in an fMRI-based semantic localiser task and variation in self-generated thoughts during the resting-state scan. Our findings showed that good performance on harder semantic tasks was associated with relative segregation at rest between frontal brain regions implicated in controlled semantic retrieval and the default mode network. Poor performance on easier tasks was linked to greater coupling between the same frontal regions and the anterior temporal lobe; a pattern associated with deliberate, verbal thematic thoughts at rest. We also identified components that related to qualities of semantic cognition: relatively good performance on pictorial semantic tasks was associated with greater separation of angular gyrus from frontal control sites and greater integration with posterior cingulate and anterior temporal cortex. In contrast, good speech production was linked to the separation of angular gyrus, posterior cingulate and temporal lobe regions. Together these data show that quantitative and qualitative variation in semantic cognition across individuals emerges from variations in the interaction of nodes within distinct functional brain networks. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington’s disease

PubMed Central

Seunarine, Kiran K.; Razi, Adeel; Cole, James H.; Gregory, Sarah; Durr, Alexandra; Roos, Raymund A. C.; Stout, Julie C.; Landwehrmeyer, Bernhard; Scahill, Rachael I.; Clark, Chris A.; Rees, Geraint

2015-01-01

Huntington’s disease can be predicted many years before symptom onset, and thus makes an ideal model for studying the earliest mechanisms of neurodegeneration. Diffuse patterns of structural connectivity loss occur in the basal ganglia and cortex early in the disease. However, the organizational principles that underlie these changes are unclear. By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level. The ‘rich club’ is a pattern of organization established in healthy human brains, where specific hub ‘rich club’ brain regions are more highly connected to each other than other brain regions. We hypothesized that selective loss of rich club connectivity might represent an organizing principle underlying the distributed pattern of structural connectivity loss seen in Huntington’s disease. To test this hypothesis we performed diffusion tractography and graph theoretical analysis in a pseudo-longitudinal study of 50 premanifest and 38 manifest Huntington’s disease participants compared with 47 healthy controls. Consistent with our hypothesis we found that structural connectivity loss selectively affected rich club brain regions in premanifest and manifest Huntington’s disease participants compared with controls. We found progressive network changes across controls, premanifest Huntington’s disease and manifest Huntington’s disease characterized by increased network segregation in the premanifest stage and loss of network integration in manifest disease. These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance. We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions. This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions. Our findings highlight the role of the rich club as a substrate for the structural connectivity loss seen in Huntington’s disease and have broader implications for understanding the connection between molecular and systems level pathology in neurodegenerative disease. PMID:26384928

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

What can autism teach us about the role of sensorimotor systems in higher cognition? New clues from studies on language, action semantics, and abstract emotional concept processing.

PubMed

Moseley, Rachel L; Pulvermüller, Friedemann

2018-03-01

Within the neurocognitive literature there is much debate about the role of the motor system in language, social communication and conceptual processing. We suggest, here, that autism spectrum conditions (ASC) may afford an excellent test case for investigating and evaluating contemporary neurocognitive models, most notably a neurobiological theory of action perception integration where widely-distributed cell assemblies linking neurons in action and perceptual brain regions act as the building blocks of many higher cognitive functions. We review a literature of functional motor abnormalities in ASC, following this with discussion of their neural correlates and aberrancies in language development, explaining how these might arise with reference to the typical formation of cell assemblies linking action and perceptual brain regions. This model gives rise to clear hypotheses regarding language comprehension, and we highlight a recent set of studies reporting differences in brain activation and behaviour in the processing of action-related and abstract-emotional concepts in individuals with ASC. At the neuroanatomical level, we discuss structural differences in long-distance frontotemporal and frontoparietal connections in ASC, such as would compromise information transfer between sensory and motor regions. This neurobiological model of action perception integration may shed light on the cognitive and social-interactive symptoms of ASC, building on and extending earlier proposals linking autistic symptomatology to motor disorder and dysfunction in action perception integration. Further investigating the contribution of motor dysfunction to higher cognitive and social impairment, we suggest, is timely and promising as it may advance both neurocognitive theory and the development of new clinical interventions for this population and others characterised by early and pervasive motor disruption. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain structure correlates of emotion-based rash impulsivity

PubMed Central

Muhlert, N.; Lawrence, A.D.

2015-01-01

Negative urgency (the tendency to engage in rash, ill-considered action in response to intense negative emotions), is a personality trait that has been linked to problematic involvement in several risky and impulsive behaviours, and to various forms of disinhibitory psychopathology, but its neurobiological correlates are poorly understood. Here, we explored whether inter-individual variation in levels of trait negative urgency was associated with inter-individual variation in regional grey matter volumes. Using voxel-based morphometry (VBM) in a sample (n = 152) of healthy participants, we found that smaller volumes of the dorsomedial prefrontal cortex and right temporal pole, regions previously linked to emotion appraisal, emotion regulation and emotion-based decision-making, were associated with higher levels of trait negative urgency. When controlling for other impulsivity linked personality traits (sensation seeking, lack of planning/perseverance) and negative emotionality per se (neuroticism), these associations remained, and an additional relationship was found between higher levels of trait negative urgency and smaller volumes of the left ventral striatum. This latter finding mirrors recent VBM findings in an animal model of impulsivity. Our findings offer novel insight into the brain structure correlates of one key source of inter-individual differences in impulsivity. PMID:25957991

Sex differences in associations between spatial ability and corpus callosum morphology.

PubMed

Kurth, Florian; Spencer, Debra; Hines, Melissa; Luders, Eileen

2018-05-10

Rotating mental representations of objects is accompanied by widespread bilateral brain activations. Thus, interhemispheric communication channels may play a relevant part when engaging in mental rotation tasks. Indeed, links between mental rotation and dimensions of the corpus callosum-the brain's main commissure system-have been reported. However, existing findings are sparse and inconsistent across studies. Here we set out to further characterize the nature of any such links, including their exact location across the corpus callosum. For this purpose, we applied an advanced image analysis approach assessing callosal thickness at 100 equidistant points in a sample of 38 healthy adults (19 men, 19 women), aged between 22 and 45 years. We detected a sex interaction, with significant structure-performance relationships in women, but not in men. Specifically, better mental rotation performance was linked to a thicker female corpus callosum within regions of the callosal splenium, posterior midbody, and anterior third. These findings may suggest sex differences in problem solving strategies where in women, more than in men, stronger interhemispheric connectivity-especially between occipitoparietal, frontal, and prefrontal regions-is associated with improved task performance. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

A Role for Brain Stress Systems in Addiction

PubMed Central

Koob, George F.

2009-01-01

Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry. PMID:18614026

Chronic Stress Modulates Regional Cerebral Glucose Transporter Expression in an Age-Specific and Sexually-Dimorphic Manner

PubMed Central

Kelly, Sean D.; Harrell, Constance S.; Neigh, Gretchen N.

2014-01-01

Facilitative glucose transporters (GLUT) mediate glucose uptake across the blood-brain-barrier into neurons and glia. Deficits in specific cerebral GLUT isoforms are linked to developmental and neurological dysfunction, but less is known about the range of variation in cerebral GLUT expression in normal conditions and the effects of environmental influences on cerebral GLUT expression. Knowing that puberty is a time of increased cerebral plasticity, metabolic demand, and shifts in hormonal balance for males and females, we first assessed gene expression of five GLUT subtypes in four brain regions in male and female adolescent and adult Wistar rats. The data indicated that sex differences in GLUT expression were most profound in the hypothalamus, and the transition from adolescence to adulthood had the most profound effect on GLUT expression in the hippocampus. Next, given the substantial energetic demands during adolescence and prior demonstrations of the adverse effects of adolescent stress, we determined the extent to which chronic stress altered GLUT expression in males and females in both adolescence and adulthood. Chronic stress significantly altered cerebral GLUT expression in males and females throughout both developmental stages but in a sexually dimorphic and brain region-specific manner. Collectively, our data demonstrate that cerebral GLUTs are expressed differentially based on brain region, sex, age, and stress exposure. These results suggest that developmental and environmental factors influence GLUT expression in multiple brain regions. Given the importance of appropriate metabolic balance within the brain, further assessment of the functional implications of life stage and environmentally-induced changes in GLUTs are warranted. PMID:24382486

Examining Brain Morphometry Associated with Self-Esteem in Young Adults Using Multilevel-ROI-Features-Based Classification Method

PubMed Central

Peng, Bo; Lu, Jieru; Saxena, Aditya; Zhou, Zhiyong; Zhang, Tao; Wang, Suhong; Dai, Yakang

2017-01-01

Purpose: This study is to exam self-esteem related brain morphometry on brain magnetic resonance (MR) images using multilevel-features-based classification method. Method: The multilevel region of interest (ROI) features consist of two types of features: (i) ROI features, which include gray matter volume, white matter volume, cerebrospinal fluid volume, cortical thickness, and cortical surface area, and (ii) similarity features, which are based on similarity calculation of cortical thickness between ROIs. For each feature type, a hybrid feature selection method, comprising of filter-based and wrapper-based algorithms, is used to select the most discriminating features. ROI features and similarity features are integrated by using multi-kernel support vector machines (SVMs) with appropriate weighting factor. Results: The classification performance is improved by using multilevel ROI features with an accuracy of 96.66%, a specificity of 96.62%, and a sensitivity of 95.67%. The most discriminating ROI features that are related to self-esteem spread over occipital lobe, frontal lobe, parietal lobe, limbic lobe, temporal lobe, and central region, mainly involving white matter and cortical thickness. The most discriminating similarity features are distributed in both the right and left hemisphere, including frontal lobe, occipital lobe, limbic lobe, parietal lobe, and central region, which conveys information of structural connections between different brain regions. Conclusion: By using ROI features and similarity features to exam self-esteem related brain morphometry, this paper provides a pilot evidence that self-esteem is linked to specific ROIs and structural connections between different brain regions. PMID:28588470

Examining Brain Morphometry Associated with Self-Esteem in Young Adults Using Multilevel-ROI-Features-Based Classification Method.

PubMed

Peng, Bo; Lu, Jieru; Saxena, Aditya; Zhou, Zhiyong; Zhang, Tao; Wang, Suhong; Dai, Yakang

2017-01-01

Purpose: This study is to exam self-esteem related brain morphometry on brain magnetic resonance (MR) images using multilevel-features-based classification method. Method: The multilevel region of interest (ROI) features consist of two types of features: (i) ROI features, which include gray matter volume, white matter volume, cerebrospinal fluid volume, cortical thickness, and cortical surface area, and (ii) similarity features, which are based on similarity calculation of cortical thickness between ROIs. For each feature type, a hybrid feature selection method, comprising of filter-based and wrapper-based algorithms, is used to select the most discriminating features. ROI features and similarity features are integrated by using multi-kernel support vector machines (SVMs) with appropriate weighting factor. Results: The classification performance is improved by using multilevel ROI features with an accuracy of 96.66%, a specificity of 96.62%, and a sensitivity of 95.67%. The most discriminating ROI features that are related to self-esteem spread over occipital lobe, frontal lobe, parietal lobe, limbic lobe, temporal lobe, and central region, mainly involving white matter and cortical thickness. The most discriminating similarity features are distributed in both the right and left hemisphere, including frontal lobe, occipital lobe, limbic lobe, parietal lobe, and central region, which conveys information of structural connections between different brain regions. Conclusion: By using ROI features and similarity features to exam self-esteem related brain morphometry, this paper provides a pilot evidence that self-esteem is linked to specific ROIs and structural connections between different brain regions.

On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth

PubMed Central

Wang, Wei-Chun; Brashier, Nadia M.; Wing, Erik A.; Marsh, Elizabeth J.; Cabeza, Roberto

2016-01-01

The “illusory truth” effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency or the subjective ease experienced while processing a statement underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency. PMID:26765947

Decoding the neural mechanisms of human tool use

PubMed Central

Gallivan, Jason P; McLean, D Adam; Valyear, Kenneth F; Culham, Jody C

2013-01-01

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas in parietal and occipitotemporal regions implicated in tool-related processing the coding remained selectively linked to upcoming actions of the tool. The highly specialized and hierarchical nature of this coding suggests that hand- and tool-related actions are represented separately at earlier levels of sensorimotor processing before becoming integrated in frontoparietal cortex. DOI: http://dx.doi.org/10.7554/eLife.00425.001 PMID:23741616

Neural Representation of Subjective Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2016-10-01

Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans.

PubMed

Crézé, Camille; Candal, Laura; Cros, Jérémy; Knebel, Jean-François; Seyssel, Kevin; Stefanoni, Nathalie; Schneiter, Philippe; Murray, Micah M; Tappy, Luc; Toepel, Ulrike

2018-05-15

Whether non-nutritive sweetener (NNS) consumption impacts food intake behavior in humans is still unclear. Discrepant sensory and metabolic signals are proposed to mislead brain regulatory centers, in turn promoting maladaptive food choices favoring weight gain. We aimed to assess whether ingestion of sucrose- and NNS-sweetened drinks would differently alter brain responses to food viewing and food intake. Eighteen normal-weight men were studied in a fasted condition and after consumption of a standardized meal accompanied by either a NNS-sweetened (NNS), or a sucrose-sweetened (SUC) drink, or water (WAT). Their brain responses to visual food cues were assessed by means of electroencephalography (EEG) before and 45 min after meal ingestion. Four hours after meal ingestion, spontaneous food intake was monitored during an ad libitum buffet. With WAT, meal intake led to increased neural activity in the dorsal prefrontal cortex and the insula, areas linked to cognitive control and interoception. With SUC, neural activity in the insula increased as well, but decreased in temporal regions linked to food categorization, and remained unchanged in dorsal prefrontal areas. The latter modulations were associated with a significantly lower total energy intake at buffet (mean kcal ± SEM; 791 ± 62) as compared to WAT (942 ± 71) and NNS (917 ± 70). In contrast to WAT and SUC, NNS consumption did not impact activity in the insula, but led to increased neural activity in ventrolateral prefrontal regions linked to the inhibition of reward. Total energy intake at the buffet was not significantly different between WAT and NNS. Our findings highlight the differential impact of caloric and non-caloric sweeteners on subsequent brain responses to visual food cues and energy intake. These variations may reflect an initial stage of adaptation to taste-calorie uncoupling, and could be indicative of longer-term consequences of repeated NNS consumption on food intake behavior.

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

PubMed

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

2016-06-01

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

Prairie Voles as a Model for Understanding the Genetic and Epigenetic Regulation of Attachment Behaviors.

PubMed

Sadino, Julie M; Donaldson, Zoe R

2018-04-06

Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related but nonmonogamous meadow and montane voles have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species. In particular, diversity in vasopressin 1a receptor (V1aR) distribution has been linked to individual and species differences in monogamy-related behaviors such as partner preference, mate guarding, and space use. Given the importance of differential receptor expression for regulating social behavior, a critical question has emerged: What are the genetic and epigenetic mechanisms that underlie brain-region-specific receptor patterns? This review will summarize what is known about how the vasopressin (AVP)-V1aR axis regulates social behaviors via signaling in discrete brain regions. From this work, we propose that brain-region-specific regulatory mechanisms facilitate robust evolvability of V1aR expression to generate diverse sociobehavioral traits. Translationally, we provide a perspective on how these studies have contributed to our understanding of human social behaviors and how brain-region-specific regulatory mechanisms might be harnessed for targeted therapies to treat social deficits in psychiatric disorders such as depression, complicated grief, and autism spectrum disorder.

Psychosocial Stress and Brain Function in Adolescent Psychopathology.

PubMed

Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

2017-08-01

The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Linking brain-wide multivoxel activation patterns to behaviour: Examples from language and math

PubMed Central

Raizada, Rajeev D.S.; Tsao, Feng-Ming; Liu, Huei-Mei; Holloway, Ian D.; Ansari, Daniel; Kuhl, Patricia K.

2010-01-01

A key goal of cognitive neuroscience is to find simple and direct connections between brain and behaviour. However, fMRI analysis typically involves choices between many possible options, with each choice potentially biasing any brain–behaviour correlations that emerge. Standard methods of fMRI analysis assess each voxel individually, but then face the problem of selection bias when combining those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI analysis methods use classifiers to analyse multiple voxels together, but can also introduce selection bias via data-reduction steps as feature selection of voxels, pre-selecting activated regions, or principal components analysis. We show here that strong brain–behaviour links can be revealed without any voxel selection or data reduction, using just plain linear regression as a classifier applied to the whole brain at once, i.e. treating each entire brain volume as a single multi-voxel pattern. The brain–behaviour correlations emerged despite the fact that the classifier was not provided with any information at all about subjects' behaviour, but instead was given only the neural data and its condition-labels. Surprisingly, more powerful classifiers such as a linear SVM and regularised logistic regression produce very similar results. We discuss some possible reasons why the very simple brain-wide linear regression model is able to find correlations with behaviour that are as strong as those obtained on the one hand from a specific ROI and on the other hand from more complex classifiers. In a manner which is unencumbered by arbitrary choices, our approach offers a method for investigating connections between brain and behaviour which is simple, rigorous and direct. PMID:20132896

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

PubMed

Batista, Andre F; Forny-Germano, Leticia; Clarke, Julia R; Lyra E Silva, Natalia M; Brito-Moreira, Jordano; Boehnke, Susan E; Winterborn, Andrew; Coe, Brian C; Lablans, Ann; Vital, Juliana F; Marques, Suelen A; Martinez, Ana Mb; Gralle, Matthias; Holscher, Christian; Klein, William L; Houzel, Jean-Christophe; Ferreira, Sergio T; Munoz, Douglas P; De Felice, Fernanda G

2018-05-01

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Local activity determines functional connectivity in the resting human brain: a simultaneous FDG-PET/fMRI study.

PubMed

Riedl, Valentin; Bienkowska, Katarzyna; Strobel, Carola; Tahmasian, Masoud; Grimmer, Timo; Förster, Stefan; Friston, Karl J; Sorg, Christian; Drzezga, Alexander

2014-04-30

Over the last decade, synchronized resting-state fluctuations of blood oxygenation level-dependent (BOLD) signals between remote brain areas [so-called BOLD resting-state functional connectivity (rs-FC)] have gained enormous relevance in systems and clinical neuroscience. However, the neural underpinnings of rs-FC are still incompletely understood. Using simultaneous positron emission tomography/magnetic resonance imaging we here directly investigated the relationship between rs-FC and local neuronal activity in humans. Computational models suggest a mechanistic link between the dynamics of local neuronal activity and the functional coupling among distributed brain regions. Therefore, we hypothesized that the local activity (LA) of a region at rest determines its rs-FC. To test this hypothesis, we simultaneously measured both LA (glucose metabolism) and rs-FC (via synchronized BOLD fluctuations) during conditions of eyes closed or eyes open. During eyes open, LA increased in the visual system, and the salience network (i.e., cingulate and insular cortices) and the pattern of elevated LA coincided almost exactly with the spatial pattern of increased rs-FC. Specifically, the voxelwise regional profile of LA in these areas strongly correlated with the regional pattern of rs-FC among the same regions (e.g., LA in primary visual cortex accounts for ∼ 50%, and LA in anterior cingulate accounts for ∼ 20% of rs-FC with the visual system). These data provide the first direct evidence in humans that local neuronal activity determines BOLD FC at rest. Beyond its relevance for the neuronal basis of coherent BOLD signal fluctuations, our procedure may translate into clinical research particularly to investigate potentially aberrant links between local dynamics and remote functional coupling in patients with neuropsychiatric disorders.

Altered hypothalamic response to food in smokers123

PubMed Central

Geha, Paul Y; Aschenbrenner, Katja; Felsted, Jennifer; O'Malley, Stephanie S; Small, Dana M

2013-01-01

Background: Smoking cessation is often followed by weight gain. Eating behaviors and weight change have been linked to the brain response to food, but it is unknown whether smoking influences this response. Objective: We determined the influence of smoking status (smokers compared with nonsmokers) on the brain response to food in regions associated with weight changes in nonsmokers. Design: In study 1, we used functional MRI (fMRI) to identify regions of the brain associated with weight change in nonsmokers. BMI and the brain response to a milk shake, which is a palatable and energy-dense food, were measured in a group of 27 nonsmokers (5 men). Sixteen subjects (3 men) returned 1 y later for BMI reassessment. The change in BMI was regressed against the brain response to isolate regions associated with weight change. In study 2, to determine whether smokers showed altered responses in regions associated with weight change, we assessed the brain response to a milk shake in 11 smokers. The brain response to a milk shake compared with a tasteless control solution was assessed in 11 smokers (5 men) in comparison with a group of age-, sex- and body weight–matched nonsmokers selected from the pool of nonsmokers who participated in study 1. Results: The response in the midbrain, hypothalamus, thalamus, and ventral striatum was positively associated with weight change at the 1-y follow-up in 16 nonsmokers. Compared with nonsmokers, smokers had a greater response to milk shakes in the hypothalamus. Conclusion: Smokers display an altered brain response to food in the hypothalamus, which is an area associated with long-term weight change in nonsmokers. PMID:23235196

Brain mediators of predictive cue effects on perceived pain

PubMed Central

Atlas, Lauren Y.; Bolger, Niall; Lindquist, Martin A.; Wager, Tor D.

2010-01-01

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for low or high painful thermal stimulation, and we assessed how cues influenced human subjects’ pain reports and BOLD fMRI responses to matched levels of noxious heat. We used multi-level mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pre-task expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing. PMID:20881115

Episodic specificity induction impacts activity in a core brain network during construction of imagined future experiences

PubMed Central

Madore, Kevin P.; Szpunar, Karl K.; Addis, Donna Rose; Schacter, Daniel L.

2016-01-01

Recent behavioral work suggests that an episodic specificity induction—brief training in recollecting the details of a past experience—enhances performance on subsequent tasks that rely on episodic retrieval, including imagining future experiences, solving open-ended problems, and thinking creatively. Despite these far-reaching behavioral effects, nothing is known about the neural processes impacted by an episodic specificity induction. Related neuroimaging work has linked episodic retrieval with a core network of brain regions that supports imagining future experiences. We tested the hypothesis that key structures in this network are influenced by the specificity induction. Participants received the specificity induction or one of two control inductions and then generated future events and semantic object comparisons during fMRI scanning. After receiving the specificity induction compared with the control, participants exhibited significantly more activity in several core network regions during the construction of imagined events over object comparisons, including the left anterior hippocampus, right inferior parietal lobule, right posterior cingulate cortex, and right ventral precuneus. Induction-related differences in the episodic detail of imagined events significantly modulated induction-related differences in the construction of imagined events in the left anterior hippocampus and right inferior parietal lobule. Resting-state functional connectivity analyses with hippocampal and inferior parietal lobule seed regions and the rest of the brain also revealed significantly stronger core network coupling following the specificity induction compared with the control. These findings provide evidence that an episodic specificity induction selectively targets episodic processes that are commonly linked to key core network regions, including the hippocampus. PMID:27601666

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

PubMed

Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

2016-12-01

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

Neural Signature of DCD: A Critical Review of MRI Neuroimaging Studies

PubMed Central

Biotteau, Maëlle; Chaix, Yves; Blais, Mélody; Tallet, Jessica; Péran, Patrice; Albaret, Jean-Michel

2016-01-01

The most common neurodevelopmental disorders (e.g., developmental dyslexia (DD), autism, attention-deficit hyperactivity disorder (ADHD)) have been the subject of numerous neuroimaging studies, leading to certain brain regions being identified as neural correlates of these conditions, referring to a neural signature of disorders. Developmental coordination disorder (DCD), however, remains one of the least understood and studied neurodevelopmental disorders. Given the acknowledged link between motor difficulties and brain features, it is surprising that so few research studies have systematically explored the brains of children with DCD. The aim of the present review was to ascertain whether it is currently possible to identify a neural signature for DCD, based on the 14 magnetic resonance imaging neuroimaging studies that have been conducted in DCD to date. Our results indicate that several brain areas are unquestionably linked to DCD: cerebellum, basal ganglia, parietal lobe, and parts of the frontal lobe (medial orbitofrontal cortex and dorsolateral prefrontal cortex). However, research has been too sparse and studies have suffered from several limitations that constitute a serious obstacle to address the question of a well-established neural signature for DCD. PMID:28018285

Brain Structure Linking Delay Discounting and Academic Performance.

PubMed

Wang, Song; Kong, Feng; Zhou, Ming; Chen, Taolin; Yang, Xun; Chen, Guangxiang; Gong, Qiyong

2017-08-01

As a component of self-discipline, delay discounting refers to the ability to wait longer for preferred rewards and plays a pivotal role in shaping students' academic performance. However, the neural basis of the association between delay discounting and academic performance remains largely unknown. Here, we examined the neuroanatomical substrates underlying delay discounting and academic performance in 214 adolescents via voxel-based morphometry (VBM) by performing structural magnetic resonance imaging (S-MRI). Behaviorally, we confirmed the significant correlation between delay discounting and academic performance. Neurally, whole-brain regression analyses indicated that regional gray matter volume (rGMV) of the left dorsolateral prefrontal cortex (DLPFC) was associated with both delay discounting and academic performance. Furthermore, delay discounting partly accounted for the association between academic performance and brain structure. Differences in the rGMV of the left DLPFC related to academic performance explained over one-third of the impact of delay discounting on academic performance. Overall, these results provide the first evidence for the common neural basis linking delay discounting and academic performance. Hum Brain Mapp 38:3917-3926, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

β-Amyloid accumulation in the human brain after one night of sleep deprivation.

PubMed

Shokri-Kojori, Ehsan; Wang, Gene-Jack; Wiers, Corinde E; Demiral, Sukru B; Guo, Min; Kim, Sung Won; Lindgren, Elsa; Ramirez, Veronica; Zehra, Amna; Freeman, Clara; Miller, Gregg; Manza, Peter; Srivastava, Tansha; De Santi, Susan; Tomasi, Dardo; Benveniste, Helene; Volkow, Nora D

2018-04-24

The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18 F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep. Copyright © 2018 the Author(s). Published by PNAS.

The craving stops before you feel it: neural correlates of chocolate craving during cue exposure with response prevention.

PubMed

Frankort, Astrid; Roefs, Anne; Siep, Nicolette; Roebroeck, Alard; Havermans, Remco; Jansen, Anita

2014-06-01

Cue reactivity and craving can be influenced by cue exposure with response prevention (CERP). This study investigated the neural correlates of CERP using functional magnetic resonance imaging, while participants smelled chocolate (17 participants) or a control object (17 participants). CERP was interrupted by 7 scanning sequences measuring the brain response to neutral and chocolate pictures. Chocolate craving was hypothesized to be mirrored by activation in brain reward regions. As expected, control group craving remained similar throughout the session. A short exposure (30 min) increased chocolate craving in the experimental group, which was mirrored by significant group differences in activation in brain reward regions. Unexpectedly, a long exposure (60 min) did not lead to craving extinction in the experimental group, although craving started to decrease at this point. On a neural level, however, activation in regions of interest in the experimental group seemed to have extinguished after the long exposure, as activation levels returned to or fell below control group levels. These results indicate that brain reward activation during CERP is linked to craving, at least for a short exposure. Regarding a longer exposure, the decline in brain reward activation in the experimental group may be a precursor of a decrease in craving.

Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium.

PubMed

Kong, Xiang-Zhen; Mathias, Samuel R; Guadalupe, Tulio; Glahn, David C; Franke, Barbara; Crivello, Fabrice; Tzourio-Mazoyer, Nathalie; Fisher, Simon E; Thompson, Paul M; Francks, Clyde

2018-05-29

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

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.

Influence of long-term social interaction on chirping behavior, steroid levels and neurogenesis in weakly electric fish.

PubMed

Dunlap, Kent D; Chung, Michael; Castellano, James F

2013-07-01

Social interactions dramatically affect the brain and behavior of animals. Studies in birds and mammals indicate that socially induced changes in adult neurogenesis participate in the regulation of social behavior, but little is known about this relationship in fish. Here, we review studies in electric fish (Apteronotus leptorhychus) that link social stimulation, changes in electrocommunication behavior and adult neurogenesis in brain regions associated with electrocommunication. Compared with isolated fish, fish living in pairs have greater production of chirps, an electrocommunication signal, during dyadic interactions and in response to standardized artificial social stimuli. Social interaction also promotes neurogenesis in the periventricular zone, which contributes born cells to the prepacemaker nucleus, the brain region that regulates chirping. Both long-term chirp rate and periventricular cell addition depend on the signal dynamics (amplitude and waveform variation), modulations (chirps) and novelty of the stimuli from the partner fish. Socially elevated cortisol levels and cortisol binding to glucocorticoid receptors mediate, at least in part, the effect of social interaction on chirping behavior and brain cell addition. In a closely related electric fish (Brachyhypopomus gauderio), social interaction enhances cell proliferation specifically in brain regions for electrocommunication and only during the breeding season, when social signaling is most elaborate. Together, these studies demonstrate a consistent correlation between brain cell addition and environmentally regulated chirping behavior across many social and steroidal treatments and suggest a causal relationship.

The neural correlates of maternal and romantic love.

PubMed

Bartels, Andreas; Zeki, Semir

2004-03-01

Romantic and maternal love are highly rewarding experiences. Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance. Yet almost nothing is known about their neural correlates in the human. We therefore used fMRI to measure brain activity in mothers while they viewed pictures of their own and of acquainted children, and of their best friend and of acquainted adults as additional controls. The activity specific to maternal attachment was compared to that associated to romantic love described in our earlier study and to the distribution of attachment-mediating neurohormones established by other studies. Both types of attachment activated regions specific to each, as well as overlapping regions in the brain's reward system that coincide with areas rich in oxytocin and vasopressin receptors. Both deactivated a common set of regions associated with negative emotions, social judgment and 'mentalizing', that is, the assessment of other people's intentions and emotions. We conclude that human attachment employs a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions, while it bonds individuals through the involvement of the reward circuitry, explaining the power of love to motivate and exhilarate.

The neurobiology of love.

PubMed

Zeki, S

2007-06-12

Romantic and maternal love are highly rewarding experiences. Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance. The newly developed ability to study the neural correlates of subjective mental states with brain imaging techniques has allowed neurobiologists to learn something about the neural bases of both romantic and maternal love. Both types of attachment activate regions specific to each, as well as overlapping regions in the brain's reward system that coincide with areas rich in oxytocin and vasopressin receptors. Both deactivate a common set of regions associated with negative emotions, social judgment and 'mentalizing' that is, the assessment of other people's intentions and emotions. Human attachment seems therefore to employ a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions, while it bonds individuals through the involvement of the reward circuitry, explaining the power of love to motivate and exhilarate. Yet the biological study of love, and especially romantic love, must go beyond and look for biological insights that can be derived from studying the world literature of love, and thus bring the output of the humanities into its orbit.

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Neural Correlates of Four Broad Temperament Dimensions: Testing Predictions for a Novel Construct of Personality

PubMed Central

Brown, Lucy L.; Acevedo, Bianca; Fisher, Helen E.

2013-01-01

Four suites of behavioral traits have been associated with four broad neural systems: the 1) dopamine and related norepinephrine system; 2) serotonin; 3) testosterone; 4) and estrogen and oxytocin system. A 56-item questionnaire, the Fisher Temperament Inventory (FTI), was developed to define four temperament dimensions associated with these behavioral traits and neural systems. The questionnaire has been used to suggest romantic partner compatibility. The dimensions were named: Curious/Energetic; Cautious/Social Norm Compliant; Analytical/Tough-minded; and Prosocial/Empathetic. For the present study, the FTI was administered to participants in two functional magnetic resonance imaging studies that elicited feelings of love and attachment, near-universal human experiences. Scores for the Curious/Energetic dimension co-varied with activation in a region of the substantia nigra, consistent with the prediction that this dimension reflects activity in the dopamine system. Scores for the Cautious/Social Norm Compliant dimension correlated with activation in the ventrolateral prefrontal cortex in regions associated with social norm compliance, a trait linked with the serotonin system. Scores on the Analytical/Tough-minded scale co-varied with activity in regions of the occipital and parietal cortices associated with visual acuity and mathematical thinking, traits linked with testosterone. Also, testosterone contributes to brain architecture in these areas. Scores on the Prosocial/Empathetic scale correlated with activity in regions of the inferior frontal gyrus, anterior insula and fusiform gyrus. These are regions associated with mirror neurons or empathy, a trait linked with the estrogen/oxytocin system, and where estrogen contributes to brain architecture. These findings, replicated across two studies, suggest that the FTI measures influences of four broad neural systems, and that these temperament dimensions and neural systems could constitute foundational mechanisms in personality structure and play a role in romantic partnerships. PMID:24236043

Neural correlates of four broad temperament dimensions: testing predictions for a novel construct of personality.

PubMed

Brown, Lucy L; Acevedo, Bianca; Fisher, Helen E

2013-01-01

Four suites of behavioral traits have been associated with four broad neural systems: the 1) dopamine and related norepinephrine system; 2) serotonin; 3) testosterone; 4) and estrogen and oxytocin system. A 56-item questionnaire, the Fisher Temperament Inventory (FTI), was developed to define four temperament dimensions associated with these behavioral traits and neural systems. The questionnaire has been used to suggest romantic partner compatibility. The dimensions were named: Curious/Energetic; Cautious/Social Norm Compliant; Analytical/Tough-minded; and Prosocial/Empathetic. For the present study, the FTI was administered to participants in two functional magnetic resonance imaging studies that elicited feelings of love and attachment, near-universal human experiences. Scores for the Curious/Energetic dimension co-varied with activation in a region of the substantia nigra, consistent with the prediction that this dimension reflects activity in the dopamine system. Scores for the Cautious/Social Norm Compliant dimension correlated with activation in the ventrolateral prefrontal cortex in regions associated with social norm compliance, a trait linked with the serotonin system. Scores on the Analytical/Tough-minded scale co-varied with activity in regions of the occipital and parietal cortices associated with visual acuity and mathematical thinking, traits linked with testosterone. Also, testosterone contributes to brain architecture in these areas. Scores on the Prosocial/Empathetic scale correlated with activity in regions of the inferior frontal gyrus, anterior insula and fusiform gyrus. These are regions associated with mirror neurons or empathy, a trait linked with the estrogen/oxytocin system, and where estrogen contributes to brain architecture. These findings, replicated across two studies, suggest that the FTI measures influences of four broad neural systems, and that these temperament dimensions and neural systems could constitute foundational mechanisms in personality structure and play a role in romantic partnerships.

Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

ERIC Educational Resources Information Center

Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

2008-01-01

Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

The skull roof tracks the brain during the evolution and development of reptiles including birds.

PubMed

Fabbri, Matteo; Mongiardino Koch, Nicolás; Pritchard, Adam C; Hanson, Michael; Hoffman, Eva; Bever, Gabriel S; Balanoff, Amy M; Morris, Zachary S; Field, Daniel J; Camacho, Jasmin; Rowe, Timothy B; Norell, Mark A; Smith, Roger M; Abzhanov, Arhat; Bhullar, Bhart-Anjan S

2017-10-01

Major transformations in brain size and proportions, such as the enlargement of the brain during the evolution of birds, are accompanied by profound modifications to the skull roof. However, the hypothesis of concerted evolution of shape between brain and skull roof over major phylogenetic transitions, and in particular of an ontogenetic relationship between specific regions of the brain and the skull roof, has never been formally tested. We performed 3D morphometric analyses to examine the deep history of brain and skull-roof morphology in Reptilia, focusing on changes during the well-documented transition from early reptiles through archosauromorphs, including nonavian dinosaurs, to birds. Non-avialan taxa cluster tightly together in morphospace, whereas Archaeopteryx and crown birds occupy a separate region. There is a one-to-one correspondence between the forebrain and frontal bone and the midbrain and parietal bone. Furthermore, the position of the forebrain-midbrain boundary correlates significantly with the position of the frontoparietal suture across the phylogenetic breadth of Reptilia and during the ontogeny of individual taxa. Conservation of position and identity in the skull roof is apparent, and there is no support for previous hypotheses that the avian parietal is a transformed postparietal. The correlation and apparent developmental link between regions of the brain and bony skull elements are likely to be ancestral to Tetrapoda and may be fundamental to all of Osteichthyes, coeval with the origin of the dermatocranium.

Brain hyperconnectivity in children with autism and its links to social deficits.

PubMed

Supekar, Kaustubh; Uddin, Lucina Q; Khouzam, Amirah; Phillips, Jennifer; Gaillard, William D; Kenworthy, Lauren E; Yerys, Benjamin E; Vaidya, Chandan J; Menon, Vinod

2013-11-14

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

PubMed

Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

2017-10-05

The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered Brain Dynamics in Patients With Type 1 Diabetes During Working Memory Processing.

PubMed

Embury, Christine M; Wiesman, Alex I; Proskovec, Amy L; Heinrichs-Graham, Elizabeth; McDermott, Timothy J; Lord, Grace H; Brau, Kaitlin L; Drincic, Andjela T; Desouza, Cyrus V; Wilson, Tony W

2018-06-01

It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. A critical problem in linking diabetes to cognitive impairment is that patients often have multiple comorbidities (e.g., obesity, hypertension) that have been independently linked to cognitive deficits. In the study reported here we focused on young adults with and without type 1 diabetes who were virtually free of such comorbidities. The two groups were matched on major health and demographic factors, and all participants completed a verbal working memory task during magnetoencephalographic brain imaging. We hypothesized that patients would have altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures. Accordingly, we found that patients had significantly stronger neural responses in the superior parietal cortices during memory encoding and significantly weaker activity in parietal-occipital regions during maintenance compared with control subjects. Moreover, disease duration and glycemic control were both significantly correlated with neural responses in various brain regions. In conclusion, young healthy adults with type 1 diabetes already have aberrant neural processing relative to their peers without diabetes, using compensatory responses to perform the task, and glucose management and duration may play a central role. © 2018 by the American Diabetes Association.

The brain connectome as a personalized biomarker of seizure outcomes after temporal lobectomy.

PubMed

Bonilha, Leonardo; Jensen, Jens H; Baker, Nathaniel; Breedlove, Jesse; Nesland, Travis; Lin, Jack J; Drane, Daniel L; Saindane, Amit M; Binder, Jeffrey R; Kuzniecky, Ruben I

2015-05-05

We examined whether individual neuronal architecture obtained from the brain connectome can be used to estimate the surgical success of anterior temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE). We retrospectively studied 35 consecutive patients with TLE who underwent ATL. The structural brain connectome was reconstructed from all patients using presurgical diffusion MRI. Network links in patients were standardized as Z scores based on connectomes reconstructed from healthy controls. The topography of abnormalities in linkwise elements of the connectome was assessed on subnetworks linking ipsilateral temporal with extratemporal regions. Predictive models were constructed based on the individual prevalence of linkwise Z scores >2 and based on presurgical clinical data. Patients were more likely to achieve postsurgical seizure freedom if they exhibited fewer abnormalities within a subnetwork composed of the ipsilateral hippocampus, amygdala, thalamus, superior frontal region, lateral temporal gyri, insula, orbitofrontal cortex, cingulate, and lateral occipital gyrus. Seizure-free surgical outcome was predicted by neural architecture alone with 90% specificity (83% accuracy), and by neural architecture combined with clinical data with 94% specificity (88% accuracy). Individual variations in connectome topography, combined with presurgical clinical data, may be used as biomarkers to better estimate surgical outcomes in patients with TLE. © 2015 American Academy of Neurology.

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

PubMed Central

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

2010-01-01

Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL-1β, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699

The emerging link between O-GlcNAcylation and neurological disorders.

PubMed

Ma, Xiaofeng; Li, He; He, Yating; Hao, Junwei

2017-10-01

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain's key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation's physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.

Why the Brain Knows More than We Do: Non-Conscious Representations and Their Role in the Construction of Conscious Experience

PubMed Central

Dresp-Langley, Birgitta

2011-01-01

Scientific studies have shown that non-conscious stimuli and representations influence information processing during conscious experience. In the light of such evidence, questions about potential functional links between non-conscious brain representations and conscious experience arise. This article discusses neural model capable of explaining how statistical learning mechanisms in dedicated resonant circuits could generate specific temporal activity traces of non-conscious representations in the brain. How reentrant signaling, top-down matching, and statistical coincidence of such activity traces may lead to the progressive consolidation of temporal patterns that constitute the neural signatures of conscious experience in networks extending across large distances beyond functionally specialized brain regions is then explained. PMID:24962683

Neural mechanisms of movement planning: motor cortex and beyond.

PubMed

Svoboda, Karel; Li, Nuo

2018-04-01

Neurons in motor cortex and connected brain regions fire in anticipation of specific movements, long before movement occurs. This neural activity reflects internal processes by which the brain plans and executes volitional movements. The study of motor planning offers an opportunity to understand how the structure and dynamics of neural circuits support persistent internal states and how these states influence behavior. Recent advances in large-scale neural recordings are beginning to decipher the relationship of the dynamics of populations of neurons during motor planning and movements. New behavioral tasks in rodents, together with quantified perturbations, link dynamics in specific nodes of neural circuits to behavior. These studies reveal a neural network distributed across multiple brain regions that collectively supports motor planning. We review recent advances and highlight areas where further work is needed to achieve a deeper understanding of the mechanisms underlying motor planning and related cognitive processes. Copyright © 2017. Published by Elsevier Ltd.

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

PubMed Central

Colon-Perez, Luis M; Tran, Kelvin; Thompson, Khalil; Pace, Michael C; Blum, Kenneth; Goldberger, Bruce A; Gold, Mark S; Bruijnzeel, Adriaan W; Setlow, Barry; Febo, Marcelo

2016-01-01

The abuse of ‘bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV. PMID:26997298

Brain structures in the sciences and humanities.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

2015-11-01

The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes.

PubMed

Casanova, Ramon; Espeland, Mark A; Goveas, Joseph S; Davatzikos, Christos; Gaussoin, Sarah A; Maldjian, Joseph A; Brunner, Robert L; Kuller, Lewis H; Johnson, Karen C; Mysiw, W Jerry; Wagner, Benjamin; Resnick, Susan M

2011-05-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers. Copyright © 2011 Elsevier Inc. All rights reserved.

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes

PubMed Central

Casanova, Ramon; Espeland, Mark A.; Goveas, Joseph S.; Davatzikos, Christos; Gaussoin, Sarah A.; Maldjian, Joseph A.; Brunner, Robert L.; Kuller, Lewis H.; Johnson, Karen C.; Mysiw, W. Jerry; Wagner, Benjamin; Resnick, Susan M.

2011-01-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years, however it is unknown whether this results in a broad-based characteristic pattern of effects. Structural MRI was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L1 penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and non-users. PMID:21292420

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

PubMed

Radu, Diana; Tomkinson, Birgitta; Zachrisson, Olof; Weber, Günther; de Belleroche, Jacqueline; Hirsch, Steven; Lindefors, Nils

2006-08-09

Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

2016-07-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Brain Volume Differences Associated With Hearing Impairment in Adults

PubMed Central

Vriend, Chris; Heslenfeld, Dirk J.; Versfeld, Niek J.; Kramer, Sophia E.

2018-01-01

Speech comprehension depends on the successful operation of a network of brain regions. Processing of degraded speech is associated with different patterns of brain activity in comparison with that of high-quality speech. In this exploratory study, we studied whether processing degraded auditory input in daily life because of hearing impairment is associated with differences in brain volume. We compared T1-weighted structural magnetic resonance images of 17 hearing-impaired (HI) adults with those of 17 normal-hearing (NH) controls using a voxel-based morphometry analysis. HI adults were individually matched with NH adults based on age and educational level. Gray and white matter brain volumes were compared between the groups by region-of-interest analyses in structures associated with speech processing, and by whole-brain analyses. The results suggest increased gray matter volume in the right angular gyrus and decreased white matter volume in the left fusiform gyrus in HI listeners as compared with NH ones. In the HI group, there was a significant correlation between hearing acuity and cluster volume of the gray matter cluster in the right angular gyrus. This correlation supports the link between partial hearing loss and altered brain volume. The alterations in volume may reflect the operation of compensatory mechanisms that are related to decoding meaning from degraded auditory input. PMID:29557274

A preliminary study of the effects of working memory training on brain function in Attention-Deficit/Hyperactivity Disorder

PubMed Central

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

2015-01-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (CogmedTM) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts. PMID:26138580

On aerobic exercise and behavioral and neural plasticity.

PubMed

Swain, Rodney A; Berggren, Kiersten L; Kerr, Abigail L; Patel, Ami; Peplinski, Caitlin; Sikorski, Angela M

2012-11-29

Aerobic exercise promotes rapid and profound alterations in the brain. Depending upon the pattern and duration of exercise, these changes in the brain may extend beyond traditional motor areas to regions and structures normally linked to learning, cognition, and emotion. Exercise-induced alterations may include changes in blood flow, hormone and growth factor release, receptor expression, angiogenesis, apoptosis, neurogenesis, and synaptogenesis. Together, we believe that these changes underlie elevations of mood and prompt the heightened behavioral plasticity commonly observed following adoption of a chronic exercise regimen. In the following paper, we will explore both the psychological and psychobiological literatures relating to exercise effects on brain in both human and non-human animals and will attempt to link plastic changes in these neural structures to modifications in learned behavior and emotional expression. In addition, we will explore the therapeutic potential of exercise given recent reports that aerobic exercise may serve as a neuroprotectant and can also slow cognitive decline during normal and pathological aging.

On Aerobic Exercise and Behavioral and Neural Plasticity

PubMed Central

Swain, Rodney A.; Berggren, Kiersten L.; Kerr, Abigail L.; Patel, Ami; Peplinski, Caitlin; Sikorski, Angela M.

2012-01-01

Aerobic exercise promotes rapid and profound alterations in the brain. Depending upon the pattern and duration of exercise, these changes in the brain may extend beyond traditional motor areas to regions and structures normally linked to learning, cognition, and emotion. Exercise-induced alterations may include changes in blood flow, hormone and growth factor release, receptor expression, angiogenesis, apoptosis, neurogenesis, and synaptogenesis. Together, we believe that these changes underlie elevations of mood and prompt the heightened behavioral plasticity commonly observed following adoption of a chronic exercise regimen. In the following paper, we will explore both the psychological and psychobiological literatures relating to exercise effects on brain in both human and non-human animals and will attempt to link plastic changes in these neural structures to modifications in learned behavior and emotional expression. In addition, we will explore the therapeutic potential of exercise given recent reports that aerobic exercise may serve as a neuroprotectant and can also slow cognitive decline during normal and pathological aging. PMID:24961267

Image and emotion: from outcomes to brain behavior.

PubMed

Nanda, Upali; Zhu, Xi; Jansen, Ben H

2012-01-01

A systematic review of neuroscience articles on the emotional states of fear, anxiety, and pain to understand how emotional response is linked to the visual characteristics of an image at the level of brain behavior. A number of outcome studies link exposure to visual images (with nature content) to improvements in stress, anxiety, and pain perception. However, an understanding of the underlying perceptual mechanisms has been lacking. In this article, neuroscience studies that use visual images to induce fear, anxiety, or pain are reviewed to gain an understanding of how the brain processes visual images in this context and to explore whether this processing can be linked to specific visual characteristics. The amygdala was identified as one of the key regions of the brain involved in the processing of fear, anxiety, and pain (induced by visual images). Other key areas included the thalamus, insula, and hippocampus. Characteristics of visual images such as the emotional dimension (valence/arousal), subject matter (familiarity, ambiguity, novelty, realism, and facial expressions), and form (sharp and curved contours) were identified as key factors influencing emotional processing. The broad structural properties of an image and overall content were found to have a more pivotal role in the emotional response than the specific details of an image. Insights on specific visual properties were translated to recommendations for what should be incorporated-and avoided-in healthcare environments.

BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

PubMed

Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

2015-06-12

During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. Copyright © 2015, American Association for the Advancement of Science.

Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

PubMed Central

Driessen, Terri M.; Zhao, Changjiu; Whittlinger, Anna; Williams, Horecia; Gammie, Stephen C.

2014-01-01

Neurotensin (NT) is a neuropeptide identical in mice and humans that is produced and released in many CNS regions associated with maternal behavior. NT has been linked to aspects of maternal care and previous studies have indirectly suggested that endogenous NT signaling is altered in the postpartum period. In the present study, we directly examine whether NT and its receptors exhibit altered gene expression in maternal relative to virgin outbred mice using real time quantitative PCR (qPCR) across multiple brain regions. We also examine NT protein levels using anti-NT antibodies and immunohistochemistry in specific brain regions. In the medial preoptic area (MPOA), which is critical for maternal behaviors, mRNA of NT and NT receptor 3 (Sort1) were significantly up-regulated in postpartum mice compared to virgins. NT mRNA was also elevated in postpartum females in the bed nucleus of the stria terminalis dorsal. However, in the lateral septum, NT mRNA was down-regulated in postpartum females. In the paraventricular nucleus of the hypothalamus (PVN), Ntsr1 expression was down-regulated in postpartum females. Neurotensin receptor 2 (Ntsr2) expression was not altered in any brain region tested. In terms of protein expression, NT immunohistochemistry results indicated that NT labeling was elevated in the postpartum brain in the MPOA, lateral hypothalamus, and two subregions of PVN. Together, these findings indicate that endogenous changes occur in NT and its receptors across multiple brain regions, and these likely support the emergence of some maternal behaviors. PMID:24416154

Vasopressin Proves Es-sense-tial: Vasopressin and the Modulation of Sensory Processing in Mammals

PubMed Central

Bester-Meredith, Janet K.; Fancher, Alexandria P.; Mammarella, Grace E.

2015-01-01

As mammals develop, they encounter increasing social complexity in the surrounding world. In order to survive, mammals must show appropriate behaviors toward their mates, offspring, and same-sex conspecifics. Although the behavioral effects of the neuropeptide arginine vasopressin (AVP) have been studied in a variety of social contexts, the effects of this neuropeptide on multimodal sensory processing have received less attention. AVP is widely distributed through sensory regions of the brain and has been demonstrated to modulate olfactory, auditory, gustatory, and visual processing. Here, we review the evidence linking AVP to the processing of social stimuli in sensory regions of the brain and explore how sensory processing can shape behavioral responses to these stimuli. In addition, we address the interplay between hormonal and neural AVP in regulating sensory processing of social cues. Because AVP pathways show plasticity during development, early life experiences may shape life-long processing of sensory information. Furthermore, disorders of social behavior such as autism and schizophrenia that have been linked with AVP also have been linked with dysfunctions in sensory processing. Together, these studies suggest that AVP’s diversity of effects on social behavior across a variety of mammalian species may result from the effects of this neuropeptide on sensory processing. PMID:25705203

Regional amplitude of the low-frequency fluctuations at rest predicts word-reading skill.

PubMed

Xu, M; De Beuckelaer, A; Wang, X; Liu, L; Song, Y; Liu, J

2015-07-09

Individuals' reading skills are critical for their educational development, but variation in reading skills is known to be large. The present study used functional magnetic resonance imaging (fMRI) to examine the role of spontaneous brain activity at rest in individual differences in reading skills in a large sample of participants (N=263). Specifically, we correlated individuals' word-reading skill with their fractional amplitude of low-frequency fluctuation (fALFF) of the whole brain at rest and found that the fALFFs of both the bilateral precentral gyrus (PCG) and superior temporal plane (STP) were positively associated with reading skills. The fALFF-reading association observed in these two regions remained after controlling for general cognitive abilities and in-scanner head motion. A cross-validation confirmed that the individual differences in word-reading skills were reliably correlated with the fALFF values of the bilateral PCG and STP. A follow-up task-based fMRI experiment revealed that the reading-related regions overlapped with regions showing a higher response to sentences than to pseudo-sentences (strings of pseudo-words), suggesting the resting-state brain activity partly captures the characteristics of task-based brain activity. In short, our study provides one of the first pieces of evidence that links spontaneous brain activity to reading behavior and offers an easy-to-access neural marker for evaluating reading skill. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

PubMed

Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

2014-11-01

The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

PubMed

Greven, Corina U; Bralten, Janita; Mennes, Maarten; O'Dwyer, Laurence; van Hulzen, Kimm J E; Rommelse, Nanda; Schweren, Lizanne J S; Hoekstra, Pieter J; Hartman, Catharina A; Heslenfeld, Dirk; Oosterlaan, Jaap; Faraone, Stephen V; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2015-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (β = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (β = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (β = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P < .001) and putamen (P = .01) volumes (both corrected for total brain volume) in control individuals, whereas age was unrelated to these volumes in participants with ADHD and their unaffected siblings. Attention-deficit/hyperactivity disorder was not significantly related to the other subcortical volumes. Global differences in gray matter volume may be due to alterations in the general mechanisms underlying normal brain development in ADHD. The age-by-diagnosis interaction in the caudate and putamen supports the relevance of different brain developmental trajectories in participants with ADHD vs control individuals and supports the role of subcortical basal ganglia alterations in the pathophysiology of ADHD. Alterations in total gray matter and caudate and putamen volumes in unaffected siblings suggest that these volumes are linked to familial risk for ADHD.

Differential alpha coherence hemispheric patterns in men and women during pleasant and unpleasant musical emotions.

PubMed

Flores-Gutiérrez, Enrique O; Díaz, José-Luis; Barrios, Fernando A; Guevara, Miguel Angel; Del Río-Portilla, Yolanda; Corsi-Cabrera, María; Del Flores-Gutiérrez, Enrique O

2009-01-01

Potential sex differences in EEG coherent activity during pleasant and unpleasant musical emotions were investigated. Musical excerpts by Mahler, Bach, and Prodromidès were played to seven men and seven women and their subjective emotions were evaluated in relation to alpha band intracortical coherence. Different brain links in specific frequencies were associated to pleasant and unpleasant emotions. Pleasant emotions (Mahler, Bach) increased upper alpha couplings linking left anterior and posterior regions. Unpleasant emotions (Prodromidès) were sustained by posterior midline coherence exclusively in the right hemisphere in men and bilateral in women. Combined music induced bilateral oscillations among posterior sensory and predominantly left association areas in women. Consistent with their greater positive attributions to music, the coherent network is larger in women, both for musical emotion and for unspecific musical effects. Musical emotion entails specific coupling among cortical regions and involves coherent upper alpha activity between posterior association areas and frontal regions probably mediating emotional and perceptual integration. Linked regions by combined music suggest more working memory contribution in women and attention in men.

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks

PubMed Central

Kim, Minkyung; Kim, Seunghwan; Mashour, George A.; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are “progressive and earlier” or “abrupt but delayed” account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations. PMID:28713258

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks.

PubMed

Kim, Minkyung; Kim, Seunghwan; Mashour, George A; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are "progressive and earlier" or "abrupt but delayed" account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations.

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

PubMed

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

2017-09-01

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

Tau, amyloid, and cascading network failure across the Alzheimer's disease spectrum.

PubMed

Jones, David T; Graff-Radford, Jonathan; Lowe, Val J; Wiste, Heather J; Gunter, Jeffrey L; Senjem, Matthew L; Botha, Hugo; Kantarci, Kejal; Boeve, Bradley F; Knopman, David S; Petersen, Ronald C; Jack, Clifford R

2017-12-01

Functionally related brain regions are selectively vulnerable to Alzheimer's disease pathophysiology. However, molecular markers of this pathophysiology (i.e., beta-amyloid and tau aggregates) have discrepant spatial and temporal patterns of progression within these selectively vulnerable brain regions. Existing reductionist pathophysiologic models cannot account for these large-scale spatiotemporal inconsistencies. Within the framework of the recently proposed cascading network failure model of Alzheimer's disease, however, these large-scale patterns are to be expected. This model postulates the following: 1) a tau-associated, circumscribed network disruption occurs in brain regions specific to a given phenotype in clinically normal individuals; 2) this disruption can trigger phenotype independent, stereotypic, and amyloid-associated compensatory brain network changes indexed by changes in the default mode network; 3) amyloid deposition marks a saturation of functional compensation and portends an acceleration of the inciting phenotype specific, and tau-associated, network failure. With the advent of in vivo molecular imaging of tau pathology, combined with amyloid and functional network imaging, it is now possible to investigate the relationship between functional brain networks, tau, and amyloid across the disease spectrum within these selectively vulnerable brain regions. In a large cohort (n = 218) spanning the Alzheimer's disease spectrum from young, amyloid negative, cognitively normal subjects to Alzheimer's disease dementia, we found several distinct spatial patterns of tau deposition, including 'Braak-like' and 'non-Braak-like', across functionally related brain regions. Rather than arising focally and spreading sequentially, elevated tau signal seems to occur system-wide based on inferences made from multiple cross-sectional analyses we conducted looking at regional patterns of tau signal. Younger age-of-disease-onset was associated with 'non-Braak-like' patterns of tau, suggesting an association with atypical clinical phenotypes. As predicted by the cascading network failure model of Alzheimer's disease, we found that amyloid is a partial mediator of the relationship between functional network failure and tau deposition in functionally connected brain regions. This study implicates large-scale brain networks in the pathophysiology of tau deposition and offers support to models incorporating large-scale network physiology into disease models linking tau and amyloid, such as the cascading network failure model of Alzheimer's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The experience of beauty derived from sorrow

PubMed Central

2017-01-01

Abstract We studied the neural mechanisms that are engaged during the experience of beauty derived from sorrow and from joy, two experiences that share a common denominator (beauty) but are linked to opposite emotional valences. Twenty subjects viewed and rerated, in a functional magnetic resonance imaging scanner, 120 images which each had classified into the following four categories: beautiful and sad; beautiful and joyful; neutral; ugly. The medial orbito‐frontal cortex (mOFC) was active during the experience of both types of beauty. Otherwise, the two experiences engaged different parts of the brain: joyful beauty engaged areas linked to positive emotions while sorrowful beauty engaged areas linked to negative experiences. Separate regions of the cerebellum were engaged during experience of the two conditions. A functional connectivity analysis indicated that the activity within the mOFC was modulated by the supplementary motor area/middle cingulate cortex, known to be engaged during empathetic experiences provoked by other peoples' sadness. Hum Brain Mapp 38:4185–4200, 2017. © 2017 Wiley Periodicals, Inc. PMID:28544456

Linking Resting-State Networks in the Prefrontal Cortex to Executive Function: A Functional Near Infrared Spectroscopy Study.

PubMed

Zhao, Jia; Liu, Jiangang; Jiang, Xin; Zhou, Guifei; Chen, Guowei; Ding, Xiao P; Fu, Genyue; Lee, Kang

2016-01-01

Executive function (EF) plays vital roles in our everyday adaptation to the ever-changing environment. However, limited existing studies have linked EF to the resting-state brain activity. The functional connectivity in the resting state between the sub-regions of the brain can reveal the intrinsic neural mechanisms involved in cognitive processing of EF without disturbance from external stimuli. The present study investigated the relations between the behavioral executive function (EF) scores and the resting-state functional network topological properties in the Prefrontal Cortex (PFC). We constructed complex brain functional networks in the PFC from 90 healthy young adults using functional near infrared spectroscopy (fNIRS). We calculated the correlations between the typical network topological properties (regional topological properties and global topological properties) and the scores of both the Total EF and components of EF measured by computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB). We found that the Total EF scores were positively correlated with regional properties in the right dorsal superior frontal gyrus (SFG), whereas the opposite pattern was found in the right triangular inferior frontal gyrus (IFG). Different EF components were related to different regional properties in various PFC areas, such as planning in the right middle frontal gyrus (MFG), working memory mainly in the right MFG and triangular IFG, short-term memory in the left dorsal SFG, and task switch in the right MFG. In contrast, there were no significant findings for global topological properties. Our findings suggested that the PFC plays an important role in individuals' behavioral performance in the executive function tasks. Further, the resting-state functional network can reveal the intrinsic neural mechanisms involved in behavioral EF abilities.

A 2.5-D Representation of the Human Hand

ERIC Educational Resources Information Center

Longo, Matthew R.; Haggard, Patrick

2012-01-01

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

Aging and walnut-rich diet supplementation affects the expression of immediate-early genes in critical brain regions

USDA-ARS?s Scientific Manuscript database

Emerging evidence indicates a direct link between age-associated changes in epigenetic mechanisms and onset of neurodegenerative diseases, and that these genomic modulations are directly affected by diet. Diets deficient in folate, choline and methionine, or the trace elements zinc and selenium, are...

Effects of aging and walnut diet on DNA methylation and expression of immediate-early genes in critical brain regions

USDA-ARS?s Scientific Manuscript database

Emerging evidence indicates a direct link between age-associated changes in epigenetic mechanisms and onset of neurodegenerative diseases, and that these genomic modulations are directly affected by the diet. Diets deficient in folate, choline and methionine, or the trace elements zinc and selenium,...

Female hatchling American kestrels have a larger hippocampus than males: A link with sexual size dimorphism?

USGS Publications Warehouse

Guigueno, Melanie F.; Karouna-Renier, Natalie K.; Henry, Paula F. P.; Head, Jessica A.; Peters, Lisa E.; Palace, Vince P.; Letcher, Robert J.; Fernie, Kimberly J.

2018-01-01

The brain and underlying cognition may vary adaptively according to an organism’s ecology. As with all raptor species, adult American kestrels (Falco sparverius) are sexually dimorphic with females being larger than males. Related to this sexual dimorphism, kestrels display sex differences in hunting and migration, with females ranging more widely than males, suggesting possible sex differences in spatial cognition. However, hippocampus volume, the brain region responsible for spatial cognition, has not been investigated in raptors. Here, we measured hippocampus and telencephalon volumes in American kestrel hatchlings. Female hatchlings had a significantly larger hippocampus relative to the telencephalon and brain weight than males (∼12% larger), although telencephalon volume relative to brain weight and body size was similar between the sexes. The magnitude of this hippocampal sex difference is similar to that reported between male and female polygynous Microtus voles and migratory and non-migratory subspecies of Zonotrichia sparrows. Future research should determine if this sex difference in relative hippocampus volume of hatchling kestrels persists into adulthood and if similar patterns exist in other raptor species, thus potentially linking sex differences in the brain to sex differences of space use of adults in the wild.

Resting-state Abnormalities in Heroin-dependent Individuals.

PubMed

Pandria, Niki; Kovatsi, Leda; Vivas, Ana B; Bamidis, Panagiotis D

2018-05-15

Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions

PubMed Central

Muhlert, Nils; Atzori, Matteo; De Vita, Enrico; Thomas, David L; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Geurts, Jeroen J G; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2014-01-01

Objective Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance. Methods Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent 1H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. Regression models investigated the association between glutamate concentration and memory performance independently of magnetisation transfer ratio values and grey matter lesions withint he same regions, and whole-brain grey matter volume. Results Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls. Conclusions The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS. PMID:24431465

Influence of long-term social interaction on chirping behavior, steroid levels and neurogenesis in weakly electric fish

PubMed Central

Dunlap, Kent D.; Chung, Michael; Castellano, James F.

2013-01-01

Summary Social interactions dramatically affect the brain and behavior of animals. Studies in birds and mammals indicate that socially induced changes in adult neurogenesis participate in the regulation of social behavior, but little is known about this relationship in fish. Here, we review studies in electric fish (Apteronotus leptorhychus) that link social stimulation, changes in electrocommunication behavior and adult neurogenesis in brain regions associated with electrocommunication. Compared with isolated fish, fish living in pairs have greater production of chirps, an electrocommunication signal, during dyadic interactions and in response to standardized artificial social stimuli. Social interaction also promotes neurogenesis in the periventricular zone, which contributes born cells to the prepacemaker nucleus, the brain region that regulates chirping. Both long-term chirp rate and periventricular cell addition depend on the signal dynamics (amplitude and waveform variation), modulations (chirps) and novelty of the stimuli from the partner fish. Socially elevated cortisol levels and cortisol binding to glucocorticoid receptors mediate, at least in part, the effect of social interaction on chirping behavior and brain cell addition. In a closely related electric fish (Brachyhypopomus gauderio), social interaction enhances cell proliferation specifically in brain regions for electrocommunication and only during the breeding season, when social signaling is most elaborate. Together, these studies demonstrate a consistent correlation between brain cell addition and environmentally regulated chirping behavior across many social and steroidal treatments and suggest a causal relationship. PMID:23761468

Discrete Neural Signatures of Basic Emotions.

PubMed

Saarimäki, Heini; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P; Lampinen, Jouko; Vuilleumier, Patrik; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

2016-06-01

Categorical models of emotions posit neurally and physiologically distinct human basic emotions. We tested this assumption by using multivariate pattern analysis (MVPA) to classify brain activity patterns of 6 basic emotions (disgust, fear, happiness, sadness, anger, and surprise) in 3 experiments. Emotions were induced with short movies or mental imagery during functional magnetic resonance imaging. MVPA accurately classified emotions induced by both methods, and the classification generalized from one induction condition to another and across individuals. Brain regions contributing most to the classification accuracy included medial and inferior lateral prefrontal cortices, frontal pole, precentral and postcentral gyri, precuneus, and posterior cingulate cortex. Thus, specific neural signatures across these regions hold representations of different emotional states in multimodal fashion, independently of how the emotions are induced. Similarity of subjective experiences between emotions was associated with similarity of neural patterns for the same emotions, suggesting a direct link between activity in these brain regions and the subjective emotional experience. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Testosterone affects language areas of the adult human brain

PubMed Central

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.

2016-01-01

Abstract 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. PMID:26876303

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

PubMed Central

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

2011-01-01

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

Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

PubMed

Cao, Miao; He, Yong; Dai, Zhengjia; Liao, Xuhong; Jeon, Tina; Ouyang, Minhui; Chalak, Lina; Bi, Yanchao; Rollins, Nancy; Dong, Qi; Huang, Hao

2017-03-01

Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The zinc dyshomeostasis hypothesis of Alzheimer's disease.

PubMed

Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline.

A Putative Mechanism of Age-Related Synaptic Dysfunction Based on the Impact of IGF-1 Receptor Signaling on Synaptic CaMKIIα Phosphorylation.

PubMed

Ogundele, Olalekan M; Pardo, Joaquin; Francis, Joseph; Goya, Rodolfo G; Lee, Charles C

2018-01-01

Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca 2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways. These proteins (CaMKIIα and MAPK) regulate Ca 2+ movement and long-term potentiation (LTP). Since IGF-1R controls the synaptic activity of Ca 2+ , CaMKIIα and MAPK signaling, the possible mechanism through which an age-dependent change in IGF-1R can alter the synaptic expression and phosphorylation of these proteins in aging needs to be investigated. In this study, we evaluated the relationship between an age-dependent change in brain IGF-1R and phosphorylation of CaMKIIα/MAPK. Furthermore, we elucidated possible mechanisms through which dysregulated CaMKIIα/MAPK interaction may be linked to a change in neurotransmitter processing and synaptic function. Male C57BL/6 VGAT-Venus mice at postnatal days 80 (P80), 365 and 730 were used to study age-related neural changes in two brain regions associated with cognitive function: hippocampus and prefrontal cortex (PFC). By means of high throughput confocal imaging and quantitative immunoblotting, we evaluated the distribution and expression of IGF-1, IGF-1R, CaMKIIα, p-CaMKIIα, MAPK and p-MAPK in whole brain lysate, hippocampus and cortex. Furthermore, we compared protein expression patterns and regional changes at P80, P365 and P730. Ultimately, we determined the relative phosphorylation pattern of CaMKIIα and MAPK through quantification of neural p-CaMKIIα and p-MAPK/ErK, and IGF-1R expression for P80, P365 and P730 brain samples. In addition to a change in synaptic function, our results show a decrease in neural IGF-1/IGF-1R expression in whole brain, hippocampus and cortex of aged mice. This was associated with a significant upregulation of phosphorylated neural MAPK (p-MAPK) and decrease in total brain CaMKIIα (i.e., CaMKIIα and p-CaMKIIα) in the aged brain. Taken together, we showed that brain aging is associated with a change in neural IGF-1/IGF-1R expression and may be linked to a change in phosphorylation of synaptic kinases (CaMKIIα and MAPK) that are involved in the modulation of LTP.

Double Dissociation in the Anatomy of Socioemotional Disinhibition and Executive Functioning in Dementia

PubMed Central

Krueger, Casey E.; Laluz, Victor; Rosen, Howard J.; Neuhaus, John M.; Miller, Bruce L.; Kramer, Joel H.

2010-01-01

Objective To determine if socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobe, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method Subjects included 157 patients with neurodegenerative disease. A semi-automated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including three tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single factor score to represent EF. Results Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, MMSE, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition and MFG significantly predicted executive functioning performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. Conclusions These results support a specific association between orbitofrontal areas and behavioral management as compared to dorsolateral areas and EF. PMID:21381829

Bilingual experience and resting-state brain connectivity: Impacts of L2 age of acquisition and social diversity of language use on control networks.

PubMed

Gullifer, Jason W; Chai, Xiaoqian J; Whitford, Veronica; Pivneva, Irina; Baum, Shari; Klein, Denise; Titone, Debra

2018-05-01

We investigated the independent contributions of second language (L2) age of acquisition (AoA) and social diversity of language use on intrinsic brain organization using seed-based resting-state functional connectivity among highly proficient French-English bilinguals. There were two key findings. First, earlier L2 AoA related to greater interhemispheric functional connectivity between homologous frontal brain regions, and to decreased reliance on proactive executive control in an AX-Continuous Performance Task completed outside the scanner. Second, greater diversity in social language use in daily life related to greater connectivity between the anterior cingulate cortex and the putamen bilaterally, and to increased reliance on proactive control in the same task. These findings suggest that early vs. late L2 AoA links to a specialized neural framework for processing two languages that may engage a specific type of executive control (e.g., reactive control). In contrast, higher vs. lower degrees of diversity in social language use link to a broadly distributed set of brain networks implicated in proactive control and context monitoring. Copyright © 2018 Elsevier Ltd. All rights reserved.

CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.

PubMed

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L; Precht, Patricia; Mughal, Mohamed R; Wood, William H; Zhang, Yonqing; Becker, Kevin G; Mattson, Mark P; Pazin, Michael J

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease.

CHD5, a Brain-Specific Paralog of Mi2 Chromatin Remodeling Enzymes, Regulates Expression of Neuronal Genes

PubMed Central

Potts, Rebecca Casaday; Zhang, Peisu; Wurster, Andrea L.; Precht, Patricia; Mughal, Mohamed R.; Wood, William H.; Zhang, Yonqing; Becker, Kevin G.; Mattson, Mark P.; Pazin, Michael J.

2011-01-01

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease. PMID:21931736

Neuroanatomical and Cognitive Mediators of Age-Related Differences in Episodic Memory

PubMed Central

Head, Denise; Rodrigue, Karen M.; Kennedy, Kristen M.; Raz, Naftali

2009-01-01

Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. PMID:18590361

Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities.

PubMed

Geier, Christian; Lehnertz, Klaus

2017-02-01

Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics.

Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

PubMed

Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2017-05-09

Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study.

PubMed

Dores, A R; Almeida, I; Barbosa, F; Castelo-Branco, M; Monteiro, L; Reis, M; de Sousa, L; Caldas, A Castro

2013-01-01

Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed. The effect of emotional valence and visualization types and their interaction were analyzed through a 3 × 2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios' valence) and their interaction with three-dimensionality.

Ex vivo MR volumetry of human brain hemispheres.

PubMed

Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

2014-01-01

The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

Ex-vivo MR Volumetry of Human Brain Hemispheres

PubMed Central

Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

2013-01-01

Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

PubMed

Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Words in Context: The Effects of Length, Frequency, and Predictability on Brain Responses During Natural Reading

PubMed Central

Schuster, Sarah; Hawelka, Stefan; Hutzler, Florian; Kronbichler, Martin; Richlan, Fabio

2016-01-01

Word length, frequency, and predictability count among the most influential variables during reading. Their effects are well-documented in eye movement studies, but pertinent evidence from neuroimaging primarily stem from single-word presentations. We investigated the effects of these variables during reading of whole sentences with simultaneous eye-tracking and functional magnetic resonance imaging (fixation-related fMRI). Increasing word length was associated with increasing activation in occipital areas linked to visual analysis. Additionally, length elicited a U-shaped modulation (i.e., least activation for medium-length words) within a brain stem region presumably linked to eye movement control. These effects, however, were diminished when accounting for multiple fixation cases. Increasing frequency was associated with decreasing activation within left inferior frontal, superior parietal, and occipito-temporal regions. The function of the latter region—hosting the putative visual word form area—was originally considered as limited to sublexical processing. An exploratory analysis revealed that increasing predictability was associated with decreasing activation within middle temporal and inferior frontal regions previously implicated in memory access and unification. The findings are discussed with regard to their correspondence with findings from single-word presentations and with regard to neurocognitive models of visual word recognition, semantic processing, and eye movement control during reading. PMID:27365297

Seasonal changes and sexual dimorphism in gene expression of StAR protein, steroidogenic enzymes and sex hormone receptors in the frog brain.

PubMed

Santillo, Alessandra; Falvo, Sara; Di Fiore, Maria Maddalena; Chieffi Baccari, Gabriella

2017-05-15

The brain of amphibians contains all the key enzymes of steroidogenesis and has a high steroidogenic activity. In seasonally-breeding amphibian species brain steroid levels fluctuate synchronously with the reproductive cycle. Here we report a study of gene expression of StAR protein, key steroidogenic enzymes and sex hormone receptors in the telencephalon (T) and diencephalon-mesencephalon (D-M) of male and female reproductive and post-reproductive Pelophylax esculentus, a seasonally breeding anuran amphibian. Significant differences in gene expression were observed between (a) the reproductive and post-reproductive phase, (b) the two brain regions and (c) male and female frogs. During the reproductive phase, star gene expression increased in the male (both T and D-M) but not in the female brain. Seasonal fluctuations in expression levels of hsd3b1, hsd17b1, srd5a1 and cyp19a1 genes for neurosteroidogenic enzymes occurred in D-M region of both sexes, with the higher levels in reproductive period. Moreover, the D-M region generally showed higher levels of gene expression than the T region in both sexes. Gene expression was higher in females than males for most genes, suggesting higher neurosteroid production in female brain. Seasonal and sex-linked changes were also observed in gene expression for androgen (ar) and estrogen (esr1, esr2) receptors, with the males showing the highest ar levels in reproductive phase and the highest esr1 and esr2 levels in post-reproductive phase; in contrast, females showed the maximum expression for all three genes in reproductive phase. The results are the first evidence for seasonal changes and sexual dimorphism of gene expression of the neurosteroidogenic pathway in amphibians. Copyright © 2016 Elsevier Inc. All rights reserved.

Graph Theory at the Service of Electroencephalograms.

PubMed

Iakovidou, Nantia D

2017-04-01

The brain is one of the largest and most complex organs in the human body and EEG is a noninvasive electrophysiological monitoring method that is used to record the electrical activity of the brain. Lately, the functional connectivity in human brain has been regarded and studied as a complex network using EEG signals. This means that the brain is studied as a connected system where nodes, or units, represent different specialized brain regions and links, or connections, represent communication pathways between the nodes. Graph theory and theory of complex networks provide a variety of measures, methods, and tools that can be useful to efficiently model, analyze, and study EEG networks. This article is addressed to computer scientists who wish to be acquainted and deal with the study of EEG data and also to neuroscientists who would like to become familiar with graph theoretic approaches and tools to analyze EEG data.

Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

PubMed

Kolla, Nathan J; Dunlop, Katharine; Meyer, Jeffrey H; Downar, Jonathan

2018-05-09

The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

V. Multi-level analysis of cortical neuroanatomy in Williams syndrome.

PubMed

Galaburda, A M; Bellugi, U

2000-01-01

The purpose of a neuroanatomical analysis of Williams Syndrome (WMS) brains is to help bridge the knowledge of the genetics of this disorder with the knowledge on behavior. Here, we outline findings of cortical neuroanatomy at multiple levels. We describe the gross anatomy with respect to brain shape, cortical folding, and asymmetry. This, as with most neuroanatomical information available in the literature on anatomical-functional correlations, links up best to the behavioral profile. Then, we describe the cytoarchitectonic appearance of the cortex. Further, we report on some histometric results. Finally, we present findings of immunocytochemistry that attempt to link up to the genomic deletion. The gross anatomical findings consist mainly of a small brain that shows curtailment in the posterior-parietal and occipital regions. There is also subtle dysmorphism of cortical folding. A consistent finding is a short central sulcus that does not become opercularized in the interhemispheric fissure, bringing attention to a possible developmental anomaly affecting the dorsal half of the hemispheres. There is also lack of asymmetry in the planum temporale. The cortical cytoarchitecture is relatively normal, with all sampled areas showing features typical of the region from which they are taken. Measurements in area 17 show increased cell size and decreased cell-packing density, which address the issue of possible abnormal connectivity. Immunostaining shows absence of elastin but normal staining for Lim-1 kinase, both of which are products of genes that are part of the deletion. Finally, one serially sectioned brain shows a fair amount of acquired pathology of microvascular origin related most likely to underlying hypertension and heart disease.

Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

PubMed

Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

2017-08-15

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance

PubMed Central

Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C.

2015-01-01

Objective To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Materials and methods Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. Results The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9–14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. Conclusions The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer’s disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted. PMID:26650926

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

PubMed

Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

2015-01-01

To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Drawing Inspiration from Human Brain Networks: Construction of Interconnected Virtual Networks

PubMed Central

Kominami, Daichi; Leibnitz, Kenji; Murata, Masayuki

2018-01-01

Virtualization of wireless sensor networks (WSN) is widely considered as a foundational block of edge/fog computing, which is a key technology that can help realize next-generation Internet of things (IoT) networks. In such scenarios, multiple IoT devices and service modules will be virtually deployed and interconnected over the Internet. Moreover, application services are expected to be more sophisticated and complex, thereby increasing the number of modifications required for the construction of network topologies. Therefore, it is imperative to establish a method for constructing a virtualized WSN (VWSN) topology that achieves low latency on information transmission and high resilience against network failures, while keeping the topological construction cost low. In this study, we draw inspiration from inter-modular connectivity in human brain networks, which achieves high performance when dealing with large-scale networks composed of a large number of modules (i.e., regions) and nodes (i.e., neurons). We propose a method for assigning inter-modular links based on a connectivity model observed in the cerebral cortex of the brain, known as the exponential distance rule (EDR) model. We then choose endpoint nodes of these links by controlling inter-modular assortativity, which characterizes the topological connectivity of brain networks. We test our proposed methods using simulation experiments. The results show that the proposed method based on the EDR model can construct a VWSN topology with an optimal combination of communication efficiency, robustness, and construction cost. Regarding the selection of endpoint nodes for the inter-modular links, the results also show that high assortativity enhances the robustness and communication efficiency because of the existence of inter-modular links of two high-degree nodes. PMID:29642483

Drawing Inspiration from Human Brain Networks: Construction of Interconnected Virtual Networks.

PubMed

Murakami, Masaya; Kominami, Daichi; Leibnitz, Kenji; Murata, Masayuki

2018-04-08

Virtualization of wireless sensor networks (WSN) is widely considered as a foundational block of edge/fog computing, which is a key technology that can help realize next-generation Internet of things (IoT) networks. In such scenarios, multiple IoT devices and service modules will be virtually deployed and interconnected over the Internet. Moreover, application services are expected to be more sophisticated and complex, thereby increasing the number of modifications required for the construction of network topologies. Therefore, it is imperative to establish a method for constructing a virtualized WSN (VWSN) topology that achieves low latency on information transmission and high resilience against network failures, while keeping the topological construction cost low. In this study, we draw inspiration from inter-modular connectivity in human brain networks, which achieves high performance when dealing with large-scale networks composed of a large number of modules (i.e., regions) and nodes (i.e., neurons). We propose a method for assigning inter-modular links based on a connectivity model observed in the cerebral cortex of the brain, known as the exponential distance rule (EDR) model. We then choose endpoint nodes of these links by controlling inter-modular assortativity, which characterizes the topological connectivity of brain networks. We test our proposed methods using simulation experiments. The results show that the proposed method based on the EDR model can construct a VWSN topology with an optimal combination of communication efficiency, robustness, and construction cost. Regarding the selection of endpoint nodes for the inter-modular links, the results also show that high assortativity enhances the robustness and communication efficiency because of the existence of inter-modular links of two high-degree nodes.

Neuronal correlates of the five factor model (FFM) of human personality: Multimodal imaging in a large healthy sample.

PubMed

Bjørnebekk, Astrid; Fjell, Anders M; Walhovd, Kristine B; Grydeland, Håkon; Torgersen, Svenn; Westlye, Lars T

2013-01-15

Advances in neuroimaging techniques have recently provided glimpse into the neurobiology of complex traits of human personality. Whereas some intriguing findings have connected aspects of personality to variations in brain morphology, the relations are complex and our current understanding is incomplete. Therefore, we aimed to provide a comprehensive investigation of brain-personality relations using a multimodal neuroimaging approach in a large sample comprising 265 healthy individuals. The NEO Personality Inventory was used to provide measures of core aspects of human personality, and imaging phenotypes included measures of total and regional brain volumes, regional cortical thickness and arealization, and diffusion tensor imaging indices of white matter (WM) microstructure. Neuroticism was the trait most clearly linked to brain structure. Higher neuroticism including facets reflecting anxiety, depression and vulnerability to stress was associated with smaller total brain volume, widespread decrease in WM microstructure, and smaller frontotemporal surface area. Higher scores on extraversion were associated with thinner inferior frontal gyrus, and conscientiousness was negatively associated with arealization of the temporoparietal junction. No reliable associations between brain structure and agreeableness and openness, respectively, were found. The results provide novel evidence of the associations between brain structure and variations in human personality, and corroborate previous findings of a consistent neuroanatomical basis of negative emotionality. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Adolescent binge drinking linked to abnormal spatial working memory brain activation: differential gender effects.

PubMed

Squeglia, Lindsay M; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F

2011-10-01

Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Forty binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males), aged 16 to 19 years, completed neuropsychological testing, substance use interviews, and an SWM task during functional magnetic resonance imaging. Significant binge drinking status × gender interactions were found (p < 0.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (p < 0.025). For male binge drinkers, greater activation was linked to better spatial performance (p < 0.025). Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during an SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that blood oxygen level-dependent activation is affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive marker of alcohol impact to the brain on future behaviors, such as driving safety, academic performance, and neuropsychological performance. Copyright © 2011 by the Research Society on Alcoholism.

Positive Association between Cognitive Ability and Cortical Thickness in a Representative US Sample of Healthy 6 to 18 Year-Olds

ERIC Educational Resources Information Center

Karama, S.; Ad-Dab'bagh, Y.; Haier, R. J.; Deary, I. J.; Lyttelton, O. C.; Lepage, C.; Evans, A. C.

2009-01-01

Neuroimaging studies, using various modalities, have evidenced a link between the general intelligence factor (g) and regional brain function and structure in several multimodal association areas. While in the last few years, developments in computational neuroanatomy have made possible the "in vivo" quantification of cortical thickness, the…

Neurocircuitry of drug reward

PubMed Central

Ikemoto, Satoshi; Bonci, Antonello

2013-01-01

In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

PubMed

Rätsep, M T; Paolozza, A; Hickman, A F; Maser, B; Kay, V R; Mohammad, S; Pudwell, J; Smith, G N; Brien, D; Stroman, P W; Adams, M A; Reynolds, J N; Croy, B A; Forkert, N D

2016-05-01

Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies. © 2016 by American Journal of Neuroradiology.

Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome.

PubMed

Woodcock, Kate A; Humphreys, Glyn W; Oliver, Chris; Hansen, Peter C

2010-12-02

We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS). PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning. The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure, and brain activity was contrasted on switching and non-switching blocks using fMRI. Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices. We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task-set reconfiguration. In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex. One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network, which has been linked to attentional control. The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes, cognition and behaviour. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

PubMed Central

2018-01-01

To understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells from Drosophila midbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes. PMID:29671739

Quantification of Transporter and Receptor Proteins in Dog Brain Capillaries and Choroid Plexus: Relevance for the Distribution in Brain and CSF of Selected BCRP and P-gp Substrates.

PubMed

Braun, Clemens; Sakamoto, Atsushi; Fuchs, Holger; Ishiguro, Naoki; Suzuki, Shinobu; Cui, Yunhai; Klinder, Klaus; Watanabe, Michitoshi; Terasaki, Tetsuya; Sauer, Achim

2017-10-02

Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, nonhuman primates, and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study was to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF. We used QTAP to examine the protein expression of 17 selected transporters and receptors at the dog BBB and BCSFB. For the first time, we directly linked the expression of two efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), to regional brain and CSF distribution using specific substrates. Two cocktails, each containing one P-gp substrate (quinidine or apafant) and one BCRP substrate (dantrolene or daidzein) were infused intravenously prior to collection of the brain. Transporter expression varied only slightly between the capillaries of different brain regions and did not result in region-specific distribution of the investigated substrates. There were, however, distinct differences between brain capillaries and choroid plexus. Largest differences were observed for BCRP and P-gp: both were highly expressed in brain capillaries, but no BCRP and only low amounts of P-gp were detected in the choroid plexus. K p,uu,brain and K p,uu,CSF of both P-gp substrates were indicative of drug efflux. Also, K p,uu,brain for the BCRP substrates was low. In contrast, K p,uu,CSF for both BCRP substrates was close to unity, resulting in K p,uu,CSF /K p,uu,brain ratios of 7 and 8, respectively. We conclude that the drug transporter expression profiles differ between the BBB and BCSFB in dogs, that there are species differences in the expression profiles, and that CSF is not a suitable surrogate for unbound brain concentrations of BCRP substrates in dogs.

On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review

PubMed Central

Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo

2013-01-01

Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579

Social connectedness, mental health and the adolescent brain.

PubMed

Lamblin, M; Murawski, C; Whittle, S; Fornito, A

2017-09-01

Social relationships promote health and wellbeing. Brain regions regulating social behavior continue to develop throughout adolescence, as teens learn to navigate their social environment with increasing sophistication. Adolescence is also a time of increased risk for the development of psychiatric disorders, many of which are characteristically associated with social dysfunction. In this review, we consider the links between adolescent brain development and the broader social environment. We examine evidence that individual differences in social ability, partly determined by genetic influences on brain structure and function, impact the quality and quantity of social ties during adolescence and that, conversely, the structure of one's social network exerts complex yet profound influences on individual behavior and mental health. In this way, the brain and social environment sculpt each other throughout the teenage years to influence one's social standing amongst peers. Reciprocal interactions between brain maturation and the social environment at this critical developmental stage may augment risk or promote resilience for mental illness and other health outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2015-11-01

Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with psychopathy. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Structure of Cognition: Attentional Episodes in Mind and Brain

PubMed Central

Duncan, John

2013-01-01

Cognition is organized in a structured series of attentional episodes, allowing complex problems to be addressed through solution of simpler subproblems. A “multiple-demand” (MD) system of frontal and parietal cortex is active in many different kinds of tasks, and using data from neuroimaging, electrophysiology, neuropsychology, and cognitive studies of intelligence, I propose a core role for MD regions in assembly of the attentional episode. Monkey and human data show dynamic neural coding of attended information across multiple MD regions, with rapid communication within and between regions. Neuropsychological and imaging data link MD function to fluid intelligence, explaining some but not all “executive” deficits after frontal lobe lesions. Cognitive studies link fluid intelligence to goal neglect, and the problem of dividing complex task requirements into focused parts. Like the innate releasing mechanism of ethology, I suggest that construction of the attentional episode provides a core organizational principle for complex, adaptive cognition. PMID:24094101

Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled-4.

PubMed

Luhmann, Ulrich F O; Neidhardt, John; Kloeckener-Gruissem, Barbara; Schäfer, Nikolaus F; Glaus, Esther; Feil, Silke; Berger, Wolfgang

2008-05-01

X-linked Norrie disease, familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity are severe human eye diseases and can all be caused by mutations in the Norrie disease pseudoglioma gene. They all show vascular defects and characteristic features of retinal hypoxia. Only Norrie disease displays additional neurological symptoms, which are sensorineural hearing loss and mental retardation. In the present study, we analysed transcript levels of the ligand Norrin (Ndph) and its two receptors Frizzled-4 (Fzd4) and LDL-related protein receptor 5 (Lrp5) in six different brain regions (cerebellum, cortex, hippocampus, olfactory bulb, pituitary and brain stem) of 6- to 8-month-old wild-type and Ndph knockout mice by quantitative real-time PCR. No effect of the Ndph knockout allele on Fzd4 or Lrp5 receptor expression was found. Furthermore, no alterations of the transcript levels of three hypoxia-regulated angiogenic factors (Vegfa, Itgrb3 and Tie1) were observed in the absence of Norrin. Interestingly, we identified significant differences in Ndph, Fzd4 and Lrp5 transcript levels in brain regions of wild-type mice and observed highest expression of Norrin and frizzled-4 in cerebellum. Transcript analyses were correlated with morphological data obtained from cerebellum and immunohistochemical studies of blood vessels in different brain regions. Vessel density was reduced in the cerebellum of Ndph knockout mice but the number of Purkinje and granular cells was not altered. This provides the first description of a brain phenotype in Ndph knockout mice, which will help to elucidate the role of Norrin in the brain.

Neuroanatomical substrates of action perception and understanding: an anatomic likelihood estimation meta-analysis of lesion-symptom mapping studies in brain injured patients

PubMed Central

Urgesi, Cosimo; Candidi, Matteo; Avenanti, Alessio

2014-01-01

Several neurophysiologic and neuroimaging studies suggested that motor and perceptual systems are tightly linked along a continuum rather than providing segregated mechanisms supporting different functions. Using correlational approaches, these studies demonstrated that action observation activates not only visual but also motor brain regions. On the other hand, brain stimulation and brain lesion evidence allows tackling the critical question of whether our action representations are necessary to perceive and understand others’ actions. In particular, recent neuropsychological studies have shown that patients with temporal, parietal, and frontal lesions exhibit a number of possible deficits in the visual perception and the understanding of others’ actions. The specific anatomical substrates of such neuropsychological deficits however, are still a matter of debate. Here we review the existing literature on this issue and perform an anatomic likelihood estimation meta-analysis of studies using lesion-symptom mapping methods on the causal relation between brain lesions and non-linguistic action perception and understanding deficits. The meta-analysis encompassed data from 361 patients tested in 11 studies and identified regions in the inferior frontal cortex, the inferior parietal cortex and the middle/superior temporal cortex, whose damage is consistently associated with poor performance in action perception and understanding tasks across studies. Interestingly, these areas correspond to the three nodes of the action observation network that are strongly activated in response to visual action perception in neuroimaging research and that have been targeted in previous brain stimulation studies. Thus, brain lesion mapping research provides converging causal evidence that premotor, parietal and temporal regions play a crucial role in action recognition and understanding. PMID:24910603

Gene expression links functional networks across cortex and striatum.

PubMed

Anderson, Kevin M; Krienen, Fenna M; Choi, Eun Young; Reinen, Jenna M; Yeo, B T Thomas; Holmes, Avram J

2018-04-12

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.

Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.

PubMed

Haddad, Leila; Schäfer, Axel; Streit, Fabian; Lederbogen, Florian; Grimm, Oliver; Wüst, Stefan; Deuschle, Michael; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas

2015-01-01

Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Identifying disease-related subnetwork connectome biomarkers by sparse hypergraph learning.

PubMed

Zu, Chen; Gao, Yue; Munsell, Brent; Kim, Minjeong; Peng, Ziwen; Cohen, Jessica R; Zhang, Daoqiang; Wu, Guorong

2018-06-14

The functional brain network has gained increased attention in the neuroscience community because of its ability to reveal the underlying architecture of human brain. In general, majority work of functional network connectivity is built based on the correlations between discrete-time-series signals that link only two different brain regions. However, these simple region-to-region connectivity models do not capture complex connectivity patterns between three or more brain regions that form a connectivity subnetwork, or subnetwork for short. To overcome this current limitation, a hypergraph learning-based method is proposed to identify subnetwork differences between two different cohorts. To achieve our goal, a hypergraph is constructed, where each vertex represents a subject and also a hyperedge encodes a subnetwork with similar functional connectivity patterns between different subjects. Unlike previous learning-based methods, our approach is designed to jointly optimize the weights for all hyperedges such that the learned representation is in consensus with the distribution of phenotype data, i.e. clinical labels. In order to suppress the spurious subnetwork biomarkers, we further enforce a sparsity constraint on the hyperedge weights, where a larger hyperedge weight indicates the subnetwork with the capability of identifying the disorder condition. We apply our hypergraph learning-based method to identify subnetwork biomarkers in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). A comprehensive quantitative and qualitative analysis is performed, and the results show that our approach can correctly classify ASD and ADHD subjects from normal controls with 87.65 and 65.08% accuracies, respectively.

Network localization of neurological symptoms from focal brain lesions

PubMed Central

Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D.

2015-01-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10−5) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10−4). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. PMID:26264514

Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease.

PubMed

Parra, Mario A; Mikulan, Ezequiel; Trujillo, Natalia; Sala, Sergio Della; Lopera, Francisco; Manes, Facundo; Starr, John; Ibanez, Agustin

2017-01-01

Alzheimer's disease (AD) as a disconnection syndrome which disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions share pathophysiological mechanisms remains unknown. To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the Visual Short-Term Memory binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mood-dependent integration in discourse comprehension: happy and sad moods affect consistency processing via different brain networks.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2014-12-01

According to recent research on language comprehension, the semantic features of a text are not the only determinants of whether incoming information is understood as consistent. Listeners' pre-existing affective states play a crucial role as well. The current fMRI experiment examines the effects of happy and sad moods during comprehension of consistent and inconsistent story endings, focusing on brain regions previously linked to two integration processes: inconsistency detection, evident in stronger responses to inconsistent endings, and fluent processing (accumulation), evident in stronger responses to consistent endings. The analysis evaluated whether differences in the BOLD response for consistent and inconsistent story endings correlated with self-reported mood scores after a mood induction procedure. Mood strongly affected regions previously associated with inconsistency detection. Happy mood increased sensitivity to inconsistency in regions specific for inconsistency detection (e.g., left IFG, left STS), whereas sad mood increased sensitivity to inconsistency in regions less specific for language processing (e.g., right med FG, right SFG). Mood affected more weakly regions involved in accumulation of information. These results show that mood can influence activity in areas mediating well-defined language processes, and highlight that integration is the result of context-dependent mechanisms. The finding that language comprehension can involve different networks depending on people's mood highlights the brain's ability to reorganize its functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Episodic reinstatement in the medial temporal lobe.

PubMed

Staresina, Bernhard P; Henson, Richard N A; Kriegeskorte, Nikolaus; Alink, Arjen

2012-12-12

The essence of episodic memory is our ability to reexperience past events in great detail, even in the absence of external stimulus cues. Does the phenomenological reinstatement of past experiences go along with reinstating unique neural representations in the brain? And if so, how is this accomplished by the medial temporal lobe (MTL), a brain region intimately linked to episodic memory? Computational models suggest that such reinstatement (also termed "pattern completion") in cortical regions is mediated by the hippocampus, a key region of the MTL. Although recent functional magnetic resonance imaging studies demonstrated reinstatement of coarse item properties like stimulus category or task context across different brain regions, it has not yet been shown whether reinstatement can be observed at the level of individual, discrete events-arguably the defining feature of episodic memory-nor whether MTL structures like the hippocampus support this "true episodic" reinstatement. Here we show that neural activity patterns for unique word-scene combinations encountered during encoding are reinstated in human parahippocampal cortex (PhC) during retrieval. Critically, this reinstatement occurs when word-scene combinations are successfully recollected (even though the original scene is not visually presented) and does not encompass other stimulus domains (such as word-color associations). Finally, the degree of PhC reinstatement across retrieval events correlated with hippocampal activity, consistent with a role of the hippocampus in coordinating pattern completion in cortical regions.

Relationships between extraction and metabolism of glucose, blood flow, and tissue blood volume in regions of rat brain.

PubMed

Cremer, J E; Cunningham, V J; Seville, M P

1983-09-01

Studies were made on the relationships between the rate of glucose metabolism, the transport of glucose between plasma and brain, cerebral blood flow, and blood content. Conscious control rats were compared with rats with intense tremors induced with cismethrin. The influence of plasma glucose concentration was studied by fasting some animals overnight prior to the induction of tremors. Mean plasma glucose was 8.83 mM in controls, 12.57 mM in fed rats with tremors, and 4.94 mM in rats fasted overnight prior to induction of tremors. Of 12 brain regions studied, nine showed an increased rate of glucose utilization in both fed and fasted trembling rats. Cerebellum had the highest percentage increase (200%). Rates of unidirectional glucose influx in fed trembling rats were significantly greater than those in controls in eight regions. In fasted animals, rates were the same as in controls, except in cerebellum, where it was 1.6 times higher. These high rates of glucose influx at low plasma glucose concentrations were indicative of a change in kinetic parameters of glucose transport. Unidirectional glucose influx rates were transformed to estimates of maximal transport rates (Tmax), based on the Michaelis-Menten equation. Average plasma glucose concentrations in regional capillaries (c) were calculated and shown to be maintained at values close to arterial plasma glucose concentrations (Ca), in all brain regions of each group. In trembling rats, Tmax for each brain region was higher than that in controls. In fasted rats with tremors, Tmax was higher in several brain regions than in fed rats. Tmax in cerebellum was 3.37, 4.71, and 7.89 mumol g-1 min-1 in control, fed trembling, and fasted trembling rats, respectively. Blood flow increased significantly in all regions in rats with tremors and was higher in fasted than in fed animals. There was only a weak correlation between blood flow and Tmax. Blood content of several regions increased in rats with tremors, and there was a strong correlation between Tmax and tissue blood volume. Results are consistent with localized regulatory links between blood flow, capillary surface area, and glucose transport in response to metabolic demand and hypoglycaemia. These involve changes in the linear velocity of blood through capillaries and in the extent of capillary recruitment.

Characterisation of Cdkl5 transcript isoforms in rat.

PubMed

Hector, Ralph D; Dando, Owen; Ritakari, Tuula E; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

2017-03-01

CDKL5 deficiency is a severe neurological disorder caused by mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5). The predominant human CDKL5 brain isoform is a 9.7kb transcript comprised of 18 exons with a large 6.6kb 3'-untranslated region (UTR). Mammalian models of CDKL5 disorder are currently limited to mouse, and little is known about Cdkl5 in other organisms used to model neurodevelopmental disorders, such as rat. In this study we characterise, both bioinformatically and experimentally, the rat Cdkl5 gene structure and its associated transcript isoforms. New exonic regions, splice sites and UTRs are described, confirming the presence of four distinct transcript isoforms. The predominant isoform in the brain, which we name rCdkl5_1, is orthologous to the human hCDKL5_1 and mouse mCdkl5_1 isoforms and is the most highly expressed isoform across all brain regions tested. This updated gene model of Cdkl5 in rat provides a framework for studies into its protein products and provides a reference for the development of molecular therapies for testing in rat models of CDKL5 disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking.

PubMed

Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

2017-01-16

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations.

Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking

PubMed Central

Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

2017-01-01

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations. PMID:28091559

The neuroscience of musical improvisation.

PubMed

Beaty, Roger E

2015-04-01

Researchers have recently begun to examine the neural basis of musical improvisation, one of the most complex forms of creative behavior. The emerging field of improvisation neuroscience has implications not only for the study of artistic expertise, but also for understanding the neural underpinnings of domain-general processes such as motor control and language production. This review synthesizes functional magnetic resonance imagining (fMRI) studies of musical improvisation, including vocal and instrumental improvisation, with samples of jazz pianists, classical musicians, freestyle rap artists, and non-musicians. A network of prefrontal brain regions commonly linked to improvisatory behavior is highlighted, including the pre-supplementary motor area, medial prefrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex, and dorsal premotor cortex. Activation of premotor and lateral prefrontal regions suggests that a seemingly unconstrained behavior may actually benefit from motor planning and cognitive control. Yet activation of cortical midline regions points to a role of spontaneous cognition characteristic of the default network. Together, such results may reflect cooperation between large-scale brain networks associated with cognitive control and spontaneous thought. The improvisation literature is integrated with Pressing's theoretical model, and discussed within the broader context of research on the brain basis of creative cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes.

PubMed

Del Piero, Larissa B; Saxbe, Darby E; Margolin, Gayla

2016-06-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and non-linear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Basic emotion processing and the adolescent brain: Task demands, analytic approaches, and trajectories of changes

PubMed Central

Del Piero, Larissa B.; Saxbe, Darby E.; Margolin, Gayla

2016-01-01

Early neuroimaging studies suggested that adolescents show initial development in brain regions linked with emotional reactivity, but slower development in brain structures linked with emotion regulation. However, the increased sophistication of adolescent brain research has made this picture more complex. This review examines functional neuroimaging studies that test for differences in basic emotion processing (reactivity and regulation) between adolescents and either children or adults. We delineated different emotional processing demands across the experimental paradigms in the reviewed studies to synthesize the diverse results. The methods for assessing change (i.e., analytical approach) and cohort characteristics (e.g., age range) were also explored as potential factors influencing study results. Few unifying dimensions were found to successfully distill the results of the reviewed studies. However, this review highlights the potential impact of subtle methodological and analytic differences between studies, need for standardized and theory-driven experimental paradigms, and necessity of analytic approaches that are can adequately test the trajectories of developmental change that have recently been proposed. Recommendations for future research highlight connectivity analyses and nonlinear developmental trajectories, which appear to be promising approaches for measuring change across adolescence. Recommendations are made for evaluating gender and biological markers of development beyond chronological age. PMID:27038840

Linked 4-Way Multimodal Brain Differences in Schizophrenia in a Large Chinese Han Population.

PubMed

Liu, Shengfeng; Wang, Haiying; Song, Ming; Lv, Luxian; Cui, Yue; Liu, Yong; Fan, Lingzhong; Zuo, Nianming; Xu, Kaibin; Du, Yuhui; Yu, Qingbao; Luo, Na; Qi, Shile; Yang, Jian; Xie, Sangma; Li, Jian; Chen, Jun; Chen, Yunchun; Wang, Huaning; Guo, Hua; Wan, Ping; Yang, Yongfeng; Li, Peng; Lu, Lin; Yan, Hao; Yan, Jun; Wang, Huiling; Zhang, Hongxing; Zhang, Dai; Calhoun, Vince D; Jiang, Tianzi; Sui, Jing

2018-04-20

Multimodal fusion has been regarded as a promising tool to discover covarying patterns of multiple imaging types impaired in brain diseases, such as schizophrenia (SZ). In this article, we aim to investigate the covarying abnormalities underlying SZ in a large Chinese Han population (307 SZs, 298 healthy controls [HCs]). Four types of magnetic resonance imaging (MRI) features, including regional homogeneity (ReHo) from resting-state functional MRI, gray matter volume (GM) from structural MRI, fractional anisotropy (FA) from diffusion MRI, and functional network connectivity (FNC) resulted from group independent component analysis, were jointly analyzed by a data-driven multivariate fusion method. Results suggest that a widely distributed network disruption appears in SZ patients, with synchronous changes in both functional and structural regions, especially the basal ganglia network, salience network (SAN), and the frontoparietal network. Such a multimodal coalteration was also replicated in another independent Chinese sample (40 SZs, 66 HCs). Our results on auditory verbal hallucination (AVH) also provide evidence for the hypothesis that prefrontal hypoactivation and temporal hyperactivation in SZ may lead to failure of executive control and inhibition, which is relevant to AVH. In addition, impaired working memory performance was found associated with GM reduction and FA decrease in SZ in prefrontal and superior temporal area, in both discovery and replication datasets. In summary, by leveraging multiple imaging and clinical information into one framework to observe brain in multiple views, we can integrate multiple inferences about SZ from large-scale population and offer unique perspectives regarding the missing links between the brain function and structure that may not be achieved by separate unimodal analyses.

CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail.

PubMed

Rusconi, Laura; Salvatoni, Lisa; Giudici, Laura; Bertani, Ilaria; Kilstrup-Nielsen, Charlotte; Broccoli, Vania; Landsberger, Nicoletta

2008-10-31

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome (RTT), West syndrome, and X-linked infantile spasms, sharing the common feature of mental retardation and early seizures. CDKL5 is a rather uncharacterized kinase, but its involvement in RTT seems to be explained by the fact that it works upstream of MeCP2, the main cause of Rett syndrome. To understand the role of this kinase for nervous system functions and to address if molecular mechanisms are involved in regulating its distribution and activity, we studied the ontogeny of CDKL5 expression in developing mouse brains by immunostaining and Western blotting. The expression profile of CDKL5 was compared with that of MeCP2. The two proteins share a general expression profile in the adult mouse brain, but CDKL5 levels appear to be highly modulated at the regional level. Its expression is strongly induced in early postnatal stages, and in the adult brain CDKL5 is present in mature neurons, but not in astroglia. Interestingly, the presence of CDKL5 in the cell nucleus varies at the regional level of the adult brain and is developmentally regulated. CDKL5 shuttles between the cytoplasm and the nucleus and the C-terminal tail is involved in localizing the protein to the cytoplasm in a mechanism depending on active nuclear export. Accordingly, Rett derivatives containing disease-causing truncations of the C terminus are constitutively nuclear, suggesting that they might act as gain of function mutations in this cellular compartment.

Region specific changes in nonapeptide levels during client fish interactions with allopatric and sympatric cleaner fish

PubMed Central

Soares, Marta C.; Cardoso, Sónia C.; Mazzei, Renata; André, Gonçalo I.; Morais, Marta; Gozdowska, Magdalena; Kalamarz-Kubiak, Hanna; Kulczykowska, Ewa

2017-01-01

Social relationships are crucially dependent on individual ability to learn and remember ecologically relevant cues. However, the way animals recognize cues before engaging in any social interaction and how their response is regulated by brain neuromodulators remains unclear. We examined the putative involvement of arginine vasotocin (AVT) and isotocin (IT), acting at different brain regions, during fish decision-making in the context of cooperation, by trying to identify how fish distinguish and recognize the value of other social partners or species. We hypothesized that the behavioural responses of cleaner fish clients to different social contexts would be underlain by changes in brain AVT and IT levels. We have found that changes in AVT at the level of forebrain and optic tectum are linked with a response to allopatric cleaners (novel or unfamiliar stimuli) while those at cerebellum are associated with the willingness to be cleaned (in response to sympatric cleaners). On the other hand, higher brain IT levels that were solely found in the diencephalon, also in response to allopatric cleaners. Our results are the first to implicate these nonapeptides, AVT in particular, in the assessment of social cues which enable fish to engage in mutualistic activities. PMID:28683143

Variation in brain anatomy in frogs and its possible bearing on their locomotor ecology.

PubMed

Manzano, Adriana S; Herrel, Anthony; Fabre, Anne-Claire; Abdala, Virginia

2017-07-01

Despite the long-standing interest in the evolution of the brain, relatively little is known about variation in brain anatomy in frogs. Yet, frogs are ecologically diverse and, as such, variation in brain anatomy linked to differences in lifestyle or locomotor behavior can be expected. Here we present a comparative morphological study focusing on the macro- and micro-anatomy of the six regions of the brain and its choroid plexus: the olfactory bulbs, the telencephalon, the diencephalon, the mesencephalon, the rhombencephalon, and the cerebellum. We also report on the comparative anatomy of the plexus brachialis responsible for the innervation of the forelimbs. It is commonly thought that amphibians have a simplified brain organization, associated with their supposedly limited behavioral complexity and reduced motor skills. We compare frogs with different ecologies that also use their limbs in different contexts and for other functions. Our results show that brain morphology is more complex and more variable than typically assumed. Moreover, variation in brain morphology among species appears related to locomotor behavior as suggested by our quantitative analyses. Thus we propose that brain morphology may be related to the locomotor mode, at least in the frogs included in our analysis. © 2017 Anatomical Society.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

PubMed Central

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

Functional hypergraph uncovers novel covariant structures over neurodevelopment.

PubMed

Gu, Shi; Yang, Muzhi; Medaglia, John D; Gur, Ruben C; Gur, Raquel E; Satterthwaite, Theodore D; Bassett, Danielle S

2017-08-01

Brain development during adolescence is marked by substantial changes in brain structure and function, leading to a stable network topology in adulthood. However, most prior work has examined the data through the lens of brain areas connected to one another in large-scale functional networks. Here, we apply a recently developed hypergraph approach that treats network connections (edges) rather than brain regions as the unit of interest, allowing us to describe functional network topology from a fundamentally different perspective. Capitalizing on a sample of 780 youth imaged as part of the Philadelphia Neurodevelopmental Cohort, this hypergraph representation of resting-state functional MRI data reveals three distinct classes of subnetworks (hyperedges): clusters, bridges, and stars, which respectively represent homogeneously connected, bipartite, and focal architectures. Cluster hyperedges show a strong resemblance to previously-described functional modules of the brain including somatomotor, visual, default mode, and salience systems. In contrast, star hyperedges represent highly localized subnetworks centered on a small set of regions, and are distributed across the entire cortex. Finally, bridge hyperedges link clusters and stars in a core-periphery organization. Notably, developmental changes within hyperedges are ordered in a similar core-periphery fashion, with the greatest developmental effects occurring in networked hyperedges within the functional core. Taken together, these results reveal a novel decomposition of the network organization of human brain, and further provide a new perspective on the role of local structures that emerge across neurodevelopment. Hum Brain Mapp 38:3823-3835, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

PubMed

Madathil, Sindhu K; Carlson, Shaun W; Brelsfoard, Jennifer M; Ye, Ping; D'Ercole, A Joseph; Saatman, Kathryn E

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms

PubMed Central

Levi, Sonia; Finazzi, Dario

2014-01-01

Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism. PMID:24847269

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Critical dynamics on a large human Open Connectome network

NASA Astrophysics Data System (ADS)

Ódor, Géza

2016-12-01

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

Diabetes dietary management alters responses to food pictures in brain regions associated with motivation and emotion: a functional magnetic resonance imaging study.

PubMed

Chechlacz, M; Rotshtein, P; Klamer, S; Porubská, K; Higgs, S; Booth, D; Fritsche, A; Preissl, H; Abele, H; Birbaumer, N; Nouwen, A

2009-03-01

We hypothesised that living with type 2 diabetes would enhance responses to pictures of foods in brain regions known to be involved in learnt food sensory motivation and that these stronger activations would relate to scores for dietary adherence in diabetes and to measures of potential difficulties in adherence. We compared brain responses to food images of 11 people with type 2 diabetes and 12 healthy control participants, matched for age and weight, using functional magnetic resonance imaging (fMRI). Having type 2 diabetes increased responses to pictured foods in the insula, orbitofrontal cortex (OFC) and basal ganglia and, within these regions, the effect of the fat content of the foods was larger in participants with type 2 diabetes than in healthy controls. Furthermore, increased activation to food within the insula and OFC positively correlated with external eating, dietary self-efficacy and dietary self-care. In contrast, responses within subcortical structures (amygdala and basal ganglia) were positively correlated with emotional eating and rated appetite for the food stimuli and negatively correlated with dietary self-care. Type 2 diabetes is associated with changes in brain responses to food that are modulated by dietary self-care. We propose that this is linked to the need to follow a life-long restrictive diet.

Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

PubMed

Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

2018-07-04

Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

Diffeomorphic functional brain surface alignment: Functional demons.

PubMed

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

2017-08-01

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

Visual navigation in adolescents with early periventricular lesions: knowing where, but not getting there.

PubMed

Pavlova, Marina; Sokolov, Alexander; Krägeloh-Mann, Ingeborg

2007-02-01

Visual navigation in familiar and unfamiliar surroundings is an essential ingredient of adaptive daily life behavior. Recent brain imaging work helps to recognize that establishing connectivity between brain regions is of importance for successful navigation. Here, we ask whether the ability to navigate is impaired in adolescents who were born premature and suffer congenital bilateral periventricular brain damage that might affect the pathways interconnecting subcortical structures with cortex. Performance on a set of visual labyrinth tasks was significantly worse in patients with periventricular leukomalacia (PVL) as compared with premature-born controls without lesions and term-born adolescents. The ability for visual navigation inversely relates to the severity of motor disability, leg-dominated bilateral spastic cerebral palsy. This agrees with the view that navigation ability substantially improves with practice and might be compromised in individuals with restrictions in active spatial exploration. Visual navigation is negatively linked to the volumetric extent of lesions over the right parietal and frontal periventricular regions. Whereas impairments of visual processing of point-light biological motion are associated in patients with PVL with bilateral parietal periventricular lesions, navigation ability is specifically linked to the frontal lesions in the right hemisphere. We suggest that more anterior periventricular lesions impair the interrelations between the right hippocampus and cortical areas leading to disintegration of neural networks engaged in visual navigation. For the first time, we show that the severity of right frontal periventricular damage and leg-dominated motor disorders can serve as independent predictors of the visual navigation disability.

The role of insulin receptor signaling in the brain.

PubMed

Plum, Leona; Schubert, Markus; Brüning, Jens C

2005-03-01

The insulin receptor (IR) is expressed in various regions of the developing and adult brain, and its functions have become the focus of recent research. Insulin enters the central nervous system (CNS) through the blood-brain barrier by receptor-mediated transport to regulate food intake, sympathetic activity and peripheral insulin action through the inhibition of hepatic gluconeogenesis and reproductive endocrinology. On a molecular level, some of the effects of insulin converge with those of the leptin signaling machinery at the point of activation of phosphatidylinositol 3-kinase (PI3K), resulting in the regulation of ATP-dependent potassium channels. Furthermore, insulin inhibits neuronal apoptosis via activation of protein kinase B in vitro, and it regulates phosphorylation of tau, metabolism of the amyloid precursor protein and clearance of beta-amyloid from the brain in vivo. These findings indicate that neuronal IR signaling has a direct role in the link between energy homeostasis, reproduction and the development of neurodegenerative diseases.

Metabolic profiling of Alzheimer's disease brains

NASA Astrophysics Data System (ADS)

Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

2013-08-01

Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

Network localization of neurological symptoms from focal brain lesions.

PubMed

Boes, Aaron D; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S; Fox, Michael D

2015-10-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

White matter network alterations in patients with depersonalization/derealization disorder.

PubMed

Sierk, Anika; Daniels, Judith K; Manthey, Antje; Kok, Jelmer G; Leemans, Alexander; Gaebler, Michael; Lamke, Jan-Peter; Kruschwitz, Johann; Walter, Henrik

2018-06-06

Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

Brain Functional Changes before, during, and after Clinical Pain.

PubMed

Hu, X; Racek, A J; Bellile, E; Nascimento, T D; Bender, M C; Toback, R L; Burnett, D; Khatib, L; McMahan, R; Kovelman, I; Ellwood, R P; DaSilva, A F

2018-05-01

This study used an emerging brain imaging technique, functional near-infrared spectroscopy (fNIRS), to investigate functional brain activation and connectivity that modulates sometimes traumatic pain experience in a clinical setting. Hemodynamic responses were recorded at bilateral somatosensory (S1) and prefrontal cortices (PFCs) from 12 patients with dentin hypersensitivity in a dental chair before, during, and after clinical pain. Clinical dental pain was triggered with 20 consecutive descending cold stimulations (32° to 0°C) to the affected teeth. We used a partial least squares path modeling framework to link patients' clinical pain experience with recorded hemodynamic responses at sequential stages and baseline resting-state functional connectivity (RSFC). Hemodynamic responses at PFC/S1 were sequentially elicited by expectation, cold detection, and pain perception at a high-level coefficient (coefficients: 0.92, 0.98, and 0.99, P < 0.05). We found that the pain ratings were positively affected only at a moderate level of coefficients by such sequence of functional activation (coefficient: 0.52, P < 0.05) and the baseline PFC-S1 RSFC (coefficient: 0.59, P < 0.05). Furthermore, when the dental pain had finally subsided, the PFC increased its functional connection with the affected S1 orofacial region contralateral to the pain stimulus and, in contrast, decreased with the ipsilateral homuncular S1 regions ( P < 0.05). Our study indicated for the first time that patients' clinical pain experience in the dental chair can be predicted concomitantly by their baseline functional connectivity between S1 and PFC, as well as their sequence of ongoing hemodynamic responses. In addition, this linked cascade of events had immediate after-effects on the patients' brain connectivity, even when clinical pain had already ceased. Our findings offer a better understating of the ongoing impact of affective and sensory experience in the brain before, during, and after clinical dental pain.

Structure and function of complex brain networks

PubMed Central

Sporns, Olaf

2013-01-01

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

Large-brained frogs mature later and live longer.

PubMed

Yu, Xin; Zhong, Mao Jun; Li, Da Yong; Jin, Long; Liao, Wen Bo; Kotrschal, Alexander

2018-05-01

Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long-lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Social in, social out: How the brain responds to social language with more social language.

PubMed

O'Donnell, Matthew Brook; Falk, Emily B; Lieberman, Matthew D

Social connection is a fundamental human need. As such, people's brains are sensitized to social cues, such as those carried by language, and to promoting social communication. The neural mechanisms of certain key building blocks in this process, such as receptivity to and reproduction of social language, however, are not known. We combined quantitative linguistic analysis and neuroimaging to connect neural activity in brain regions used to simulate the mental states of others with exposure to, and re-transmission of, social language. Our results link findings on successful idea transmission from communication science, sociolinguistics and cognitive neuroscience to prospectively predict the degree of social language that participants utilize when re-transmitting ideas as a function of 1) initial language inputs and 2) neural activity during idea exposure.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur

PubMed Central

Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

2015-01-01

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months’ supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze.jlr Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. PMID:26063461

The Elsevier trophoblast research award lecture: Impacts of placental growth factor and preeclampsia on brain development, behaviour, and cognition.

PubMed

Rätsep, Matthew T; Hickman, Andrew F; Croy, B Anne

2016-12-01

Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf -/- brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuregulin 1 Deficiency Modulates Adolescent Stress-Induced Dendritic Spine Loss in a Brain Region-Specific Manner and Increases Complement 4 Expression in the Hippocampus.

PubMed

Clarke, David J; Chohan, Tariq W; Kassem, Mustafa S; Smith, Kristie L; Chesworth, Rose; Karl, Tim; Kuligowski, Michael P; Fok, Sandra Y; Bennett, Maxwell R; Arnold, Jonathon C

2018-03-16

One neuropathological feature of schizophrenia is a diminished number of dendritic spines in the prefrontal cortex and hippocampus. The neuregulin 1 (Nrg1) system is involved in the plasticity of dendritic spines, and chronic stress decreases dendritic spine densities in the prefrontal cortex and hippocampus. Here, we aimed to assess whether Nrg1 deficiency confers vulnerability to the effects of adolescent stress on dendritic spine plasticity. We also assessed other schizophrenia-relevant neurobiological changes such as microglial cell activation, loss of parvalbumin (PV) interneurons, and induction of complement factor 4 (C4). Adolescent male wild-type (WT) and Nrg1 heterozygous mice were subjected to chronic restraint stress before their brains underwent Golgi impregnation or immunofluorescent staining of PV interneurons, microglial cells, and C4. Stress in WT mice promoted dendritic spine loss and microglial cell activation in the prefrontal cortex and the hippocampus. However, Nrg1 deficiency rendered mice resilient to stress-induced dendritic spine loss in the infralimbic cortex and the CA3 region of the hippocampus without affecting stress-induced microglial cell activation in these brain regions. Nrg1 deficiency and adolescent stress combined to trigger increased dendritic spine densities in the prelimbic cortex. In the hippocampal CA1 region, Nrg1 deficiency accentuated stress-induced dendritic spine loss. Nrg1 deficiency increased C4 protein and decreased C4 mRNA expression in the hippocampus, and the number of PV interneurons in the basolateral amygdala. This study demonstrates that Nrg1 modulates the impact of stress on the adolescent brain in a region-specific manner. It also provides first evidence of a link between Nrg1 and C4 systems in the hippocampus.

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

PubMed

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Brain anatomical networks in world class gymnasts: a DTI tractography study.

PubMed

Wang, Bin; Fan, Yuanyuan; Lu, Min; Li, Shumei; Song, Zheng; Peng, Xiaoling; Zhang, Ruibin; Lin, Qixiang; He, Yong; Wang, Jun; Huang, Ruiwang

2013-01-15

The excellent motor skills of world class gymnasts amaze everyone. People marvel at the way they precisely control their movements and wonder how the brain structure and function of these elite athletes differ from those of non-athletes. In this study, we acquired diffusion images from thirteen world class gymnasts and fourteen matched controls, constructed their anatomical networks, and calculated the topological properties of each network based on graph theory. From a connectivity-based analysis, we found that most of the edges with increased connection density in the champions were linked to brain regions that are located in the sensorimotor, attentional, and default-mode systems. From graph-based metrics, we detected significantly greater global and local efficiency but shorter characteristic path length in the anatomical networks of the champions compared with the controls. Moreover, in the champions we found a significantly higher nodal degree and greater regional efficiency in several brain regions that correspond to motor and attention functions. These included the left precentral gyrus, left postcentral gyrus, right anterior cingulate gyrus and temporal lobes. In addition, we revealed an increase in the mean fractional anisotropy of the corticospinal tract in the champions, possibly in response to long-term gymnastic training. Our study indicates that neuroanatomical adaptations and plastic changes occur in gymnasts' brain anatomical networks either in response to long-term intensive gymnastic training or as an innate predisposition or both. Our findings may help to explain gymnastic skills at the highest levels of performance and aid in understanding the neural mechanisms that distinguish expert gymnasts from novices. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of Gestational Exposure of Cypermethrin on Postnatal Development of Brain Cytochrome P450 2D1 and 3A1 and Neurotransmitter Receptors.

PubMed

Singh, Anshuman; Mudawal, Anubha; Shukla, Rajendra K; Yadav, Sanjay; Khanna, Vinay K; Sethumadhavan, Rao; Parmar, Devendra

2015-08-01

Oral administration of low doses (1.25, 2.5, or 5 mg/kg) of cypermethrin to pregnant Wistar rats from gestation days 5 to 21 led to dose-dependent differences in the induction of cytochrome P450 2D1 (CYP2D1) and 3A1 messenger RNA (mRNA) and protein in brain regions isolated from the offsprings postnatally at 3 weeks that persisted up to adulthood (12 weeks). Similar alterations were observed in the expression of GABAergic, muscarinic, dopaminergic, and serotonergic neurotransmitter receptors in brain regions of rat offsprings. Rechallenge of the prenatally exposed offsprings at adulthood (12 weeks old) with cypermethrin (p.o., 10 mg/kg for 6 days) led to a greater magnitude of alterations in the expression of CYPs, neurotransmitter receptors, and neurotransmitter receptor binding in the brain regions when compared to the control offsprings treated at adulthood with cypermethrin or prenatally exposed offsprings. A greater magnitude of decrease was also observed in the spontaneous locomotor activity (SLA) in prenatally exposed offsprings rechallenged with cypermethrin. The present data indicating similarities in the alterations in the expression of CYPs (2D1 and 3A1) and neurotransmitter receptors in brain has led us to suggest that endogenous function regulating CYPs is possibly associated with neurotransmission processes. A greater magnitude of alterations in CYP2D1, 3A1, neurotransmitter receptors, and SLA in rechallenged animals has further provided evidence that alterations in CYPs are possibly linked with neurotransmission processes.

Local Use-Dependent Sleep in Wakefulness Links Performance Errors to Learning

PubMed Central

Quercia, Angelica; Zappasodi, Filippo; Committeri, Giorgia; Ferrara, Michele

2018-01-01

Sleep and wakefulness are no longer to be considered as discrete states. During wakefulness brain regions can enter a sleep-like state (off-periods) in response to a prolonged period of activity (local use-dependent sleep). Similarly, during nonREM sleep the slow-wave activity, the hallmark of sleep plasticity, increases locally in brain regions previously involved in a learning task. Recent studies have demonstrated that behavioral performance may be impaired by off-periods in wake in task-related regions. However, the relation between off-periods in wake, related performance errors and learning is still untested in humans. Here, by employing high density electroencephalographic (hd-EEG) recordings, we investigated local use-dependent sleep in wake, asking participants to repeat continuously two intensive spatial navigation tasks. Critically, one task relied on previous map learning (Wayfinding) while the other did not (Control). Behaviorally awake participants, who were not sleep deprived, showed progressive increments of delta activity only during the learning-based spatial navigation task. As shown by source localization, delta activity was mainly localized in the left parietal and bilateral frontal cortices, all regions known to be engaged in spatial navigation tasks. Moreover, during the Wayfinding task, these increments of delta power were specifically associated with errors, whose probability of occurrence was significantly higher compared to the Control task. Unlike the Wayfinding task, during the Control task neither delta activity nor the number of errors increased progressively. Furthermore, during the Wayfinding task, both the number and the amplitude of individual delta waves, as indexes of neuronal silence in wake (off-periods), were significantly higher during errors than hits. Finally, a path analysis linked the use of the spatial navigation circuits undergone to learning plasticity to off periods in wake. In conclusion, local sleep regulation in wakefulness, associated with performance failures, could be functionally linked to learning-related cortical plasticity. PMID:29666574

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

PubMed

Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

2018-04-16

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

Prefrontal and medial temporal contributions to episodic memory-based reasoning.

PubMed

Suzuki, Chisato; Tsukiura, Takashi; Mochizuki-Kawai, Hiroko; Shigemune, Yayoi; Iijima, Toshio

2009-03-01

Episodic memory retrieval and reasoning are fundamental psychological components of our daily lives. Although previous studies have investigated the brain regions associated with these processes separately, the neural mechanisms of reasoning based on episodic memory retrieval are largely unknown. Here, we investigated the neural correlates underlying episodic memory-based reasoning using functional magnetic resonance imaging (fMRI). During fMRI scanning, subjects performed three tasks: reasoning, episodic memory retrieval, and episodic memory-based reasoning. We identified dissociable activations related to reasoning, episodic memory retrieval, and linking processes between the two. Regions related to reasoning were identified in the left ventral prefrontal cortices (PFC), and those related to episodic memory retrieval were found in the right medial temporal lobe (MTL) regions. In addition, activations predominant in the linking process between the two were found in the left dorsal and right ventral PFC. These findings suggest that episodic memory-based reasoning is composed of at least three processes, i.e., reasoning, episodic memory retrieval, and linking processes between the two, and that activation of both the PFC and MTL is crucial in episodic memory-based reasoning. These findings are the first to demonstrate that PFC and MTL regions contribute differentially to each process in episodic memory-based reasoning.

Structural basis for serotonergic regulation of neural circuits in the mouse olfactory bulb.

PubMed

Suzuki, Yoshinori; Kiyokage, Emi; Sohn, Jaerin; Hioki, Hiroyuki; Toida, Kazunori

2015-02-01

Olfactory processing is well known to be regulated by centrifugal afferents from other brain regions, such as noradrenergic, acetylcholinergic, and serotonergic neurons. Serotonergic neurons widely innervate and regulate the functions of various brain regions. In the present study, we focused on serotonergic regulation of the olfactory bulb (OB), one of the most structurally and functionally well-defined brain regions. Visualization of a single neuron among abundant and dense fibers is essential to characterize and understand neuronal circuits. We accomplished this visualization by successfully labeling and reconstructing serotonin (5-hydroxytryptamine: 5-HT) neurons by infection with sindbis and adeno-associated virus into dorsal raphe nuclei (DRN) of mice. 5-HT synapses were analyzed by correlative confocal laser microscopy and serial-electron microscopy (EM) study. To further characterize 5-HT neuronal and network function, we analyzed whether glutamate was released from 5-HT synaptic terminals using immuno-EM. Our results are the first visualizations of complete 5-HT neurons and fibers projecting from DRN to the OB with bifurcations. We found that a single 5-HT axon can form synaptic contacts to both type 1 and 2 periglomerular cells within a single glomerulus. Through immunolabeling, we also identified vesicular glutamate transporter 3 in 5-HT neurons terminals, indicating possible glutamatergic transmission. Our present study strongly implicates the involvement of brain regions such as the DRN in regulation of the elaborate mechanisms of olfactory processing. We further provide a structure basis of the network for coordinating or linking olfactory encoding with other neural systems, with special attention to serotonergic regulation. © 2014 Wiley Periodicals, Inc.

General and specialized brain correlates for analogical reasoning: A meta-analysis of functional imaging studies.

PubMed

Hobeika, Lucie; Diard-Detoeuf, Capucine; Garcin, Béatrice; Levy, Richard; Volle, Emmanuelle

2016-05-01

Reasoning by analogy allows us to link distinct domains of knowledge and to transfer solutions from one domain to another. Analogical reasoning has been studied using various tasks that have generally required the consideration of the relationships between objects and their integration to infer an analogy schema. However, these tasks varied in terms of the level and the nature of the relationships to consider (e.g., semantic, visuospatial). The aim of this study was to identify the cerebral network involved in analogical reasoning and its specialization based on the domains of information and task specificity. We conducted a coordinate-based meta-analysis of 27 experiments that used analogical reasoning tasks. The left rostrolateral prefrontal cortex was one of the regions most consistently activated across the studies. A comparison between semantic and visuospatial analogy tasks showed both domain-oriented regions in the inferior and middle frontal gyri and a domain-general region, the left rostrolateral prefrontal cortex, which was specialized for analogy tasks. A comparison of visuospatial analogy to matrix problem tasks revealed that these two relational reasoning tasks engage, at least in part, distinct right and left cerebral networks, particularly separate areas within the left rostrolateral prefrontal cortex. These findings highlight several cognitive and cerebral differences between relational reasoning tasks that can allow us to make predictions about the respective roles of distinct brain regions or networks. These results also provide new, testable anatomical hypotheses about reasoning disorders that are induced by brain damage. Hum Brain Mapp 37:1953-1969, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Structural and resting-state MRI detects regional brain differences in young and mid-age healthy APOE-e4 carriers compared with non-APOE-e4 carriers.

PubMed

Dowell, Nicholas G; Evans, Simon L; Tofts, Paul S; King, Sarah L; Tabet, Naji; Rusted, Jennifer M

2016-05-01

The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1 -weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. Copyright © 2016 John Wiley & Sons, Ltd.

Brain structure links everyday creativity to creative achievement.

PubMed

Zhu, Wenfeng; Chen, Qunlin; Tang, Chaoying; Cao, Guikang; Hou, Yuling; Qiu, Jiang

2016-03-01

Although creativity is commonly considered to be a cornerstone of human progress and vital to all realms of our lives, its neural basis remains elusive, partly due to the different tasks and measurement methods applied in research. In particular, the neural correlates of everyday creativity that can be experienced by everyone, to some extent, are still unexplored. The present study was designed to investigate the brain structure underlying individual differences in everyday creativity, as measured by the Creative Behavioral Inventory (CBI) (N=163). The results revealed that more creative activities were significantly and positively associated with larger gray matter volume (GMV) in the regional premotor cortex (PMC), which is a motor planning area involved in the creation and selection of novel actions and inhibition. In addition, the gray volume of the PMC had a significant positive relationship with creative achievement and Art scores, which supports the notion that training and practice may induce changes in brain structures. These results indicate that everyday creativity is linked to the PMC and that PMC volume can predict creative achievement, supporting the view that motor planning may play a crucial role in creative behavior. Published by Elsevier Inc.

Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

PubMed

Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

2016-10-01

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

Modelling Cerebral Blood Flow and Temperature Using a Vascular Porous Model

NASA Astrophysics Data System (ADS)

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

2016-11-01

Macro-modelling of cerebral blood flow can assist in determining the impact of temperature intervention to reduce permanent tissue damage during instances of brain trauma. Here we present a 3D two phase fluid-porous model for simulating blood flow through the capillary region linked to intersecting 1D arterial and venous vessel trees. This combined vasculature porous (VaPor) model simulates both flow and energy balances, including heat from metabolism, using a vasculature extracted from MRI data which are expanded upon using a tree generation algorithm. Validation of temperature balance has been achieved using rodent brain data. Direct flow validation is not as straight forward due to the method used in determining regional cerebral blood flow (rCBF). In-vivo measurements are achieved using a tracer, which disagree with direct measurements of simulated flow. However, by modelling a virtual tracer, rCBF values are obtained that agree with those found in literature. Temperature profiles generated with the VaPor model show a reduction in core brain temperature after cooling the scalp not seen previously in other models.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

The neuropsychology of first impressions: Evidence from Huntington's disease.

PubMed

Sprengelmeyer, Reiner; Young, Andrew W; Baldas, Eva-Maria; Ratheiser, Iris; Sutherland, Clare A M; Müller, Hans-Peter; Grön, Georg; Süssmuth, Sigurd D; Landwehrmeyer, G Bernhard; Orth, Michael

2016-12-01

Impairments of emotion recognition have been widely documented in Huntington's disease (HD), but little is known concerning how these relate to other aspects of social cognition, including first impressions of traits such as trustworthiness and dominance. Here, we introduce a novel and sensitive method to investigate the ability to evaluate trustworthiness and dominance from facial appearance, with control tasks measuring ability to perceive differences between comparable stimuli. We used this new method together with standard tests of face perception to investigate social cognition in HD. We found that a subgroup of people with HD was impaired at perceiving trustworthiness and dominance, and that perceiving trustworthiness and dominance were correlated with impaired facial expression recognition. In addition, we used diffusion tensor imaging (DTI) to provisionally identify candidate brain regions associated with social cognition by contrasting regional functional anisotropy (FA) measures between subgroups of HD participants showing normal or impaired perception of trustworthiness and dominance, and by correlating these regional brain abnormalities with behavioural performance on tests of emotion recognition. In this way we show for the first time alterations in perception of trustworthiness and dominance in people with HD and link these to regions which may map the boundaries of the social brain. The pattern of breakdown seen in this neurodegenerative disease can thus be used to explore potential inter-relationships between different components of social cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional Neuroanatomical Evidence for the Double-Deficit Hypothesis of Developmental Dyslexia

PubMed Central

Norton, Elizabeth S.; Black, Jessica M.; Stanley, Leanne M.; Tanaka, Hiroko; Gabrieli, John D. E.; Sawyer, Carolyn; Hoeft, Fumiko

2015-01-01

The double-deficit hypothesis of dyslexia posits that both rapid naming and phonological impairments can cause reading difficulties, and that individuals who have both of these deficits show greater reading impairments compared to those with a single deficit. Despite extensive behavioral research, the brain basis of poor reading with a double-deficit has never been investigated. The goal of the study was to evaluate the double-deficit hypothesis using functional MRI. Activation patterns during a printed word rhyme judgment task in 90 children with a wide range of reading abilities showed dissociation between brain regions that were sensitive to phonological awareness (left inferior frontal and inferior parietal regions) and rapid naming (right cerebellar lobule VI). More specifically, the double-deficit group showed less activation in the fronto-parietal reading network compared to children with only a deficit in phonological awareness, who in turn showed less activation than the typically-reading group. On the other hand, the double-deficit group showed less cerebellar activation compared to children with only a rapid naming deficit, who in turn showed less activation than the typically-reading children. Functional connectivity analyses revealed that bilateral prefrontal regions were key for linking brain regions associated with phonological awareness and rapid naming, with the double-deficit group being the most aberrant in their connectivity. Our study provides the first functional neuroanatomical evidence for the double-deficit hypothesis of developmental dyslexia. PMID:24953957

Comparison of large-scale human brain functional and anatomical networks in schizophrenia.

PubMed

Nelson, Brent G; Bassett, Danielle S; Camchong, Jazmin; Bullmore, Edward T; Lim, Kelvin O

2017-01-01

Schizophrenia is a disease with disruptions in thought, emotion, and behavior. The dysconnectivity hypothesis suggests these disruptions are due to aberrant brain connectivity. Many studies have identified connectivity differences but few have been able to unify gray and white matter findings into one model. Here we develop an extension of the Network-Based Statistic (NBS) called NBSm (Multimodal Network-based statistic) to compare functional and anatomical networks in schizophrenia. Structural, resting functional, and diffusion magnetic resonance imaging data were collected from 29 chronic patients with schizophrenia and 29 healthy controls. Images were preprocessed, and average time courses were extracted for 90 regions of interest (ROI). Functional connectivity matrices were estimated by pairwise correlations between wavelet coefficients of ROI time series. Following diffusion tractography, anatomical connectivity matrices were estimated by white matter streamline counts between each pair of ROIs. Global and regional strength were calculated for each modality. NBSm was used to find significant overlap between functional and anatomical components that distinguished health from schizophrenia. Global strength was decreased in patients in both functional and anatomical networks. Regional strength was decreased in all regions in functional networks and only one region in anatomical networks. NBSm identified a distinguishing functional component consisting of 46 nodes with 113 links (p < 0.001), a distinguishing anatomical component with 47 nodes and 50 links (p = 0.002), and a distinguishing intermodal component with 26 nodes (p < 0.001). NBSm is a powerful technique for understanding network-based group differences present in both anatomical and functional data. In light of the dysconnectivity hypothesis, these results provide compelling evidence for the presence of significant overlapping anatomical and functional disruption in people with schizophrenia.

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain.

PubMed

Creeley, Catherine E; Dikranian, Krikor T; Johnson, Stephen A; Farber, Nuri B; Olney, John W

2013-06-12

In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm3) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes.

Vocal parameters that indicate threat level correlate with FOS immunolabeling in social and vocal control brain regions.

PubMed

Ellis, Jesse M S; Riters, Lauren V

2012-01-01

Transmitting information via communicative signals is integral to interacting with conspecifics, and some species achieve this task by varying vocalizations to reflect context. Although signal variation is critical to social interactions, the underlying neural control has not been studied. In response to a predator, black-capped chickadees (Poecile atricapilla) produce mobbing calls (chick-a-dee calls) with various parameters, some of which convey information about the threat stimulus. We predicted that vocal parameters indicative of threat would be associated with distinct patterns of neuronal activity within brain areas involved in social behavior and those involved in the sensorimotor control of vocal production. To test this prediction, we measured the syntax and structural aspects of chick-a-dee call production in response to a hawk model and assessed the protein product of the immediate early gene FOS in brain regions implicated in context-specific vocal and social behavior. These regions include the medial preoptic area (POM) and lateral septum (LS), as well as regions involved in vocal motor control, including the dorsomedial nucleus of the intercollicular complex and the HVC. We found correlations linking call rate (previously demonstrated to reflect threat) to labeling in the POM and LS. Labeling in the HVC correlated with the number of D notes per call, which may also signal threat level. Labeling in the call control region dorsomedial nucleus was associated with the structure of D notes and the overall number of notes, but not call rate or type of notes produced. These results suggest that the POM and LS may influence attributes of vocalizations produced in response to predators and that the brain region implicated in song control, the HVC, also influences call production. Because variation in chick-a-dee call rate indicates predator threat, we speculate that these areas could integrate with motor control regions to imbue mobbing signals with additional information about threat level. Copyright © 2011 S. Karger AG, Basel.

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Information processing in the vertebrate habenula.

PubMed

Fore, Stephanie; Palumbo, Fabrizio; Pelgrims, Robbrecht; Yaksi, Emre

2018-06-01

The habenula is a brain region that has gained increasing popularity over the recent years due to its role in processing value-related and experience-dependent information with a strong link to depression, addiction, sleep and social interactions. This small diencephalic nucleus is proposed to act as a multimodal hub or a switchboard, where inputs from different brain regions converge. These diverse inputs to the habenula carry information about the sensory world and the animal's internal state, such as reward expectation or mood. However, it is not clear how these diverse habenular inputs interact with each other and how such interactions contribute to the function of habenular circuits in regulating behavioral responses in various tasks and contexts. In this review, we aim to discuss how information processing in habenular circuits, can contribute to specific behavioral programs that are attributed to the habenula. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors.

PubMed

Heller, Elizabeth A; Cates, Hannah M; Peña, Catherine J; Sun, Haosheng; Shao, Ningyi; Feng, Jian; Golden, Sam A; Herman, James P; Walsh, Jessica J; Mazei-Robison, Michelle; Ferguson, Deveroux; Knight, Scott; Gerber, Mark A; Nievera, Christian; Han, Ming-Hu; Russo, Scott J; Tamminga, Carol S; Neve, Rachael L; Shen, Li; Zhang, H Steve; Zhang, Feng; Nestler, Eric J

2014-12-01

Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior.

Structural brain imaging correlates of ASD and ADHD across the lifespan: a hypothesis-generating review on developmental ASD-ADHD subtypes.

PubMed

Rommelse, Nanda; Buitelaar, Jan K; Hartman, Catharina A

2017-02-01

We hypothesize that it is plausible that biologically distinct developmental ASD-ADHD subtypes are present, each characterized by a distinct time of onset of symptoms, progression and combination of symptoms. The aim of the present narrative review was to explore if structural brain imaging studies may shed light on key brain areas that are linked to both ASD and ADHD symptoms and undergo significant changes during development. These findings may possibly pinpoint to brain mechanisms underlying differential developmental ASD-ADHD subtypes. To this end we brought together the literature on ASD and ADHD structural brain imaging symptoms and particularly highlight the adolescent years and beyond. Findings indicate that the vast majority of existing MRI studies has been cross-sectional and conducted in children, and sometimes did include adolescents as well, but without explicitly documenting on this age group. MRI studies documenting on age effects in adults with ASD and/or ADHD are rare, and if age is taken into account, only linear effects are examined. Data from various studies suggest that a crucial distinctive feature underlying different developmental ASD-ADHD subtypes may be the differential developmental thinning patterns of the anterior cingulate cortex and related connections towards other prefrontal regions. These regions are crucial for the development of cognitive/effortful control and socio-emotional functioning, with impairments in these features as key to both ASD and ADHD.

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

PubMed

Dezhina, Zalina; Ranlund, Siri; Kyriakopoulos, Marinos; Williams, Steve C R; Dima, Danai

2018-05-10

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.

Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR.

PubMed

Igata, Natsuki; Kakeda, Shingo; Watanabe, Keita; Ide, Satoru; Kishi, Taro; Abe, Osamu; Igata, Ryouhei; Katsuki, Asuka; Iwata, Nakao; Yoshimura, Reiji; Korogi, Yukunori

2017-06-21

Individuals with s/s genotype of serotonin transporter gene-linked promotor region (5-HTTLPR), which appear with a high frequency in Japanese, exhibit more diagnosable depression in relation to stressful life events than those with the s/l or l/l genotype. We prospectively investigated the brain volume changes in first-episode and medication naïve major depression disorder patients (MDD) with the s/s genotype in Japanese. We assessed the differences between 27 MDD with the s/s genotype and 44 healthy subjects (HS) with the same genotype using a whole-brain voxel-by-voxel statistical analysis of MRI. Gray matter volume in a brain region with significant clusters obtained via voxel-based morphometry analysis were measured and, as an exploratory analysis, evaluated for relationships to the subcategory scores (core, sleep, activity, psychic, somatic anxiety, delusion) of the Hamilton Depression Rating Scale (HAM-D) and the Social Readjustment Rating Scale (SRRS). The brain volume in the left insula lobe was significantly smaller in the MDD than in the HS. The left insula lobe volume correlated negatively with the "psychic" score of HAM-D and the SRRS. In a Japanese population with the s/s genotype, we found an atrophy of the insula in the MDD, which might be associated with "psychic" symptom and stress events.

Brain Structural Networks in Mouse Exposed to Chronic Maternal Undernutrition.

PubMed

Barbeito-Andrés, Jimena; Gleiser, Pablo M; Bernal, Valeria; Hallgrímsson, Benedikt; Gonzalez, Paula N

2018-06-01

Brain structural connectivity is known to be altered in cases of intrauterine growth restriction and premature birth, although the specific effect of maternal nutritional restriction, a common burden in human populations, has not been assessed yet. Here we analyze the effects of maternal undernutrition during pregnancy and lactation by establishing three experimental groups of female mice divided according to their diet: control (Co), moderate calorie-protein restriction (MCP) and severe protein restriction (SP). Nutritionally restricted dams gained relatively less weight during pregnancy and the body weight of the offspring was also affected by maternal undernutrition, showing global growth restriction. We performed magnetic resonance imaging (MRI) of the offspring's brains after weaning and analyzed their connectivity patterns using complex graph theory. In general, changes observed in the MCP group were more subtle than in SP. Results indicated that brain structures were not homogeneously affected by early nutritional stress. In particular, the growth of central brain regions, such as the temporo-parietal cortex, and long integrative myelinated tracts were relatively preserved, while the frequency of short tracts was relatively reduced. We also found a differential effect on network parameters: network degree, clustering, characteristic path length and small-worldness remained mainly unchanged, while the rich-club index was lower in nutritionally restricted animals. Rich-club decrease reflects an impairment in the structure by which brain regions with large number of connections tend to be more densely linked among themselves. Overall, the findings presented here support the hypothesis that chronic nutritional stress produces long-term changes in brain structural connectivity. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain Metabolic Changes in Rats following Acoustic Trauma

PubMed Central

He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

2017-01-01

Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine metabolic pathway. Our results provide the first metabolomics evidence that acoustic trauma can induce changes in multiple metabolic pathways. This pilot study also suggests that the metabolomic approach has the potential to identify acoustic trauma-specific metabolic shifts in future studies where metabolic changes are correlated with the animal's tinnitus status. PMID:28392756

A Brain Network Processing the Age of Faces

PubMed Central

Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

Specific cerebral perfusion patterns in three schizophrenia symptom dimensions.

PubMed

Stegmayer, Katharina; Strik, Werner; Federspiel, Andrea; Wiest, Roland; Bohlhalter, Stephan; Walther, Sebastian

2017-12-01

Dimensional concepts such as the Research Domain Criteria initiative have been proposed to disentangle the heterogeneity of schizophrenia. One model introduced three neurobiologically informed behavioral dimensions: language, affectivity and motor behavior. To study the brain-behavior associations of these three dimensions, we investigated whether current behavioral alterations were linked to resting state perfusion in distinct brain circuits in schizophrenia. In total, 47 patients with schizophrenia spectrum disorders and 44 healthy controls were included. Psychopathology was assessed with the Positive And Negative Syndrome Scale and the Bern Psychopathology scale (BPS). The BPS provides severity ratings of three behavioral dimensions (language, affectivity and motor). Patients were classified according to the severity of alterations (severe, mild, no) in each dimension. Whole brain resting state cerebral blood flow (CBF) was compared between patient subgroups and controls. Two symptom dimensions were associated with distinct CBF changes. Behavioral alterations in the language dimension were linked to increased CBF in Heschl's gyrus. Altered affectivity was related to increased CBF in amygdala. The ratings of motor behavior instead were not specifically associated with CBF. Investigating behavioral alterations in three schizophrenia symptom dimensions identified distinct regional CBF changes in the language and limbic brain circuits. The results demonstrate a hitherto unknown segregation of pathophysiological pathways underlying a limited number of specific symptom dimensions in schizophrenia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Changes in functional connectivity dynamics associated with vigilance network in taxi drivers.

PubMed

Shen, Hui; Li, Zhenfeng; Qin, Jian; Liu, Qiang; Wang, Lubin; Zeng, Ling-Li; Li, Hong; Hu, Dewen

2016-01-01

An increasing number of neuroimaging studies have suggested that the fluctuations of low-frequency resting-state functional connectivity (FC) are not noise but are instead linked to the shift between distinct cognitive states. However, there is very limited knowledge about whether and how the fluctuations of FC at rest are influenced by long-term training and experience. Here, we investigated how the dynamics of resting-state FC are linked to driving behavior by comparing 20 licensed taxi drivers with 20 healthy non-drivers using a sliding window approach. We found that the driving experience could be effectively decoded with 90% (p<0.001) accuracy by the amplitude of low-frequency fluctuations in some specific connections, based on a multivariate pattern analysis technique. Interestingly, the majority of these connections fell within a set of distributed regions named "the vigilance network". Moreover, the decreased amplitude of the FC fluctuations within the vigilance network in the drivers was negatively correlated with the number of years that they had driven a taxi. Furthermore, temporally quasi-stable functional connectivity segmentation revealed significant differences between the drivers and non-drivers in the dwell time of specific vigilance-related transient brain states, although the brain's repertoire of functional states was preserved. Overall, these results suggested a significant link between the changes in the time-dependent aspects of resting-state FC within the vigilance network and long-term driving experiences. The results not only improve our understanding of how the brain supports driving behavior but also shed new light on the relationship between the dynamics of functional brain networks and individual behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

PubMed

Walton, E; Hibar, D P; van Erp, T G M; Potkin, S G; Roiz-Santiañez, R; Crespo-Facorro, B; Suarez-Pinilla, P; van Haren, N E M; de Zwarte, S M C; Kahn, R S; Cahn, W; Doan, N T; Jørgensen, K N; Gurholt, T P; Agartz, I; Andreassen, O A; Westlye, L T; Melle, I; Berg, A O; Morch-Johnsen, L; Færden, A; Flyckt, L; Fatouros-Bergman, H; Jönsson, E G; Hashimoto, R; Yamamori, H; Fukunaga, M; Jahanshad, N; De Rossi, P; Piras, F; Banaj, N; Spalletta, G; Gur, R E; Gur, R C; Wolf, D H; Satterthwaite, T D; Beard, L M; Sommer, I E; Koops, S; Gruber, O; Richter, A; Krämer, B; Kelly, S; Donohoe, G; McDonald, C; Cannon, D M; Corvin, A; Gill, M; Di Giorgio, A; Bertolino, A; Lawrie, S; Nickson, T; Whalley, H C; Neilson, E; Calhoun, V D; Thompson, P M; Turner, J A; Ehrlich, S

2018-01-01

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Early Life Stress and the Anxious Brain: Evidence for A Neural Mechanism Linking Childhood Emotional Maltreatment to Anxiety in Adulthood

PubMed Central

Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Simmons, Alan N.; Sullivan, Sarah G.; Allard, Carolyn B.; Paulus, Martin P.; Stein, Murray B.

2016-01-01

Background Childhood emotional maltreatment (CEM) increases likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. Methods One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. Results During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray matter volumes also partially mediated the CEM-anxiety relationship. Conclusions Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes. PMID:26670947

Changes in visual and sensory-motor resting-state functional connectivity support motor learning by observing.

PubMed

McGregor, Heather R; Gribble, Paul L

2015-07-01

Motor learning occurs not only through direct first-hand experience but also through observation (Mattar AA, Gribble PL. Neuron 46: 153-160, 2005). When observing the actions of others, we activate many of the same brain regions involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC, Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493-1503, 2010). Links between neural systems for vision and action have been reported in neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289-2292, 2000; Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989-994, 2003), brain imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K, Rizzolatti G, Freund HJ. Eur J Neurosci 13: 400-404, 2001; Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G. Science 286: 2526-2528, 1999), and eye tracking (Flanagan JR, Johansson RS. Nature 424: 769-771, 2003) studies. Here we used a force field learning paradigm coupled with resting-state fMRI to investigate the brain areas involved in motor learning by observing. We examined changes in resting-state functional connectivity (FC) after an observational learning task and found a network consisting of V5/MT, cerebellum, and primary motor and somatosensory cortices in which changes in FC were correlated with the amount of motor learning achieved through observation, as assessed behaviorally after resting-state fMRI scans. The observed FC changes in this network are not due to visual attention to motion or observation of movement errors but rather are specifically linked to motor learning. These results support the idea that brain networks linking action observation and motor control also facilitate motor learning. Copyright © 2015 the American Physiological Society.

Changes in visual and sensory-motor resting-state functional connectivity support motor learning by observing

PubMed Central

McGregor, Heather R.

2015-01-01

Motor learning occurs not only through direct first-hand experience but also through observation (Mattar AA, Gribble PL. Neuron 46: 153–160, 2005). When observing the actions of others, we activate many of the same brain regions involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC, Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493–1503, 2010). Links between neural systems for vision and action have been reported in neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289–2292, 2000; Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989–994, 2003), brain imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K, Rizzolatti G, Freund HJ. Eur J Neurosci 13: 400–404, 2001; Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC, Rizzolatti G. Science 286: 2526–2528, 1999), and eye tracking (Flanagan JR, Johansson RS. Nature 424: 769–771, 2003) studies. Here we used a force field learning paradigm coupled with resting-state fMRI to investigate the brain areas involved in motor learning by observing. We examined changes in resting-state functional connectivity (FC) after an observational learning task and found a network consisting of V5/MT, cerebellum, and primary motor and somatosensory cortices in which changes in FC were correlated with the amount of motor learning achieved through observation, as assessed behaviorally after resting-state fMRI scans. The observed FC changes in this network are not due to visual attention to motion or observation of movement errors but rather are specifically linked to motor learning. These results support the idea that brain networks linking action observation and motor control also facilitate motor learning. PMID:25995349

Mesolimbic effects of the antidepressant fluoxetine in Holtzman rats, a genetic strain with increased vulnerability to stress

PubMed Central

Padilla, Eimeira; Shumake, Jason; Barrett, Douglas W.; Sheridan, Eva C.; Gonzalez-Lima, F.

2011-01-01

This is the first metabolic mapping study of the effects of fluoxetine after learned helplessness training. Antidepressants are the most commonly prescribed medications, but the regions underlying treatment effects in affectively disordered brains are poorly understood. We hypothesized the antidepressant action of fluoxetine would produce adaptations in mesolimbic regions after two weeks of treatment. We used Holtzman rats, a genetic strain showing susceptibility to novelty-evoked hyperactivity and stress-evoked helplessness, to map regional brain metabolic effects caused by fluoxetine treatment. Animals underwent learned helplessness, and subsequently immobility time was scored in the forced swim test (FST). On the next day, animals began receiving two weeks of fluoxetine (5 mg/kg/day) or vehicle and were retested in the FST at the end of drug treatment. Antidepressant behavioral effects of fluoxetine were analyzed using a ratio of immobility during pre- and post-treatment FST sessions. Brains were analyzed for regional metabolic activity using quantitative cytochrome oxidase histochemistry as in our previous study using congenitally helpless rats. Fluoxetine exerted a protective effect against FST-induced immobility behavior in Holtzman rats. Fluoxetine also caused a significant reduction in the mean regional metabolism of the nucleus accumbens shell and the ventral hippocampus as compared to vehicle-treated subjects. Additional networks affected by fluoxetine treatment included the prefrontal-cingulate cortex and brainstem nuclei linked to depression (e.g. habenula, dorsal raphe and interpeduncular nucleus). We concluded that corticolimbic regions such as the prefrontal-cingulate cortex, nucleus accumbens, ventral hippocampus and key brainstem nuclei represent important contributors to the neural network mediating fluoxetine antidepressant action. PMID:21376019

A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee

PubMed Central

Li, Li; MaBouDi, HaDi; Egertová, Michaela; Elphick, Maurice R.

2017-01-01

Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee (Bombus terrestris) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory. PMID:28978727

A possible structural correlate of learning performance on a colour discrimination task in the brain of the bumblebee.

PubMed

Li, Li; MaBouDi, HaDi; Egertová, Michaela; Elphick, Maurice R; Chittka, Lars; Perry, Clint J

2017-10-11

Synaptic plasticity is considered to be a basis for learning and memory. However, the relationship between synaptic arrangements and individual differences in learning and memory is poorly understood. Here, we explored how the density of microglomeruli (synaptic complexes) within specific regions of the bumblebee ( Bombus terrestris ) brain relates to both visual learning and inter-individual differences in learning and memory performance on a visual discrimination task. Using whole-brain immunolabelling, we measured the density of microglomeruli in the collar region (visual association areas) of the mushroom bodies of the bumblebee brain. We found that bumblebees which made fewer errors during training in a visual discrimination task had higher microglomerular density. Similarly, bumblebees that had better retention of the learned colour-reward associations two days after training had higher microglomerular density. Further experiments indicated experience-dependent changes in neural circuitry: learning a colour-reward contingency with 10 colours (but not two colours) does result, and exposure to many different colours may result, in changes to microglomerular density in the collar region of the mushroom bodies. These results reveal the varying roles that visual experience, visual learning and foraging activity have on neural structure. Although our study does not provide a causal link between microglomerular density and performance, the observed positive correlations provide new insights for future studies into how neural structure may relate to inter-individual differences in learning and memory. © 2017 The Authors.

The Structural Connectome of the Human Central Homeostatic Network.

PubMed

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

2016-04-01

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

Iron, transferrin and myelinogenesis

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Baron, B.; Guillou, F.

2003-09-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits.

PubMed

Tryon, Matthew S; Carter, Cameron S; Decant, Rashel; Laugero, Kevin D

2013-08-15

Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need. Chronic stress, which can induce palatable "comfort" food consumption, may trigger or reinforce neural pathways leading to stronger reactions to highly rewarding foods. We implemented functional magnetic resonance imaging (fMRI) to assess whether chronic stress influences activation in reward, motivation and executive brain regions in response to pictures of high calorie and low calorie foods in thirty women. On separate lab visits, we also assessed food intake from a snack food buffet and circulating cortisol. In women reporting higher chronic stress (HCS), pictures of high calorie foods elicited exaggerated activity in regions of the brain involving reward, motivation, and habitual decision-making. In response to pictures of high calorie food, higher chronic stress was also associated with significant deactivation in frontal regions (BA10; BA46) linked to strategic planning and emotional control. In functional connectivity analysis, HCS strengthened connectivity between amygdala and the putamen, while LCS enhanced connectivity between amygdala and the anterior cingulate and anterior prefrontal cortex (BA10). A hypocortisolemic signature and more consumption of high calorie foods from the snack buffet were observed in the HCS group. These results suggest that persistent stress exposure may alter the brain's response to food in ways that predispose individuals to poor eating habits which, if sustained, may increase risk for obesity. © 2013.

When the future becomes the past: Differences in brain activation patterns for episodic memory and episodic future thinking.

PubMed

Weiler, Julia A; Suchan, Boris; Daum, Irene

2010-10-15

Episodic memory and episodic future thinking activate a network of overlapping brain regions, but little is known about the mechanism with which the brain separates the two processes. It was recently suggested that differential activity for memory and future thinking may be linked to differences in the phenomenal properties (e.g., richness of detail). Using functional magnetic resonance imaging in healthy subjects and a novel experimental design, we investigated the networks involved in the imagery of future and the recall of past events for the same target occasion, i.e. the Christmas and New Year's holidays, thereby keeping temporal distance and content similar across conditions. Although ratings of phenomenal characteristics were comparable for future thoughts and memories, differential activation patterns emerged. The right posterior hippocampus exhibited stronger memory-related activity during early event recall, and stronger future thought-related activity during late event imagination. Other regions, e.g., the precuneus and lateral prefrontal cortex, showed the reverse activation pattern with early future-associated and late past-associated activation. Memories compared to future thoughts were further related to stronger activation in several visual processing regions, which accords with a reactivation of the original perceptual experience. In conclusion, the results showed for the first time unique neural signatures for both memory and future thinking even in the absence of differences in phenomenal properties and suggested different time courses of brain activation for episodic memory and future thinking. Copyright 2010 Elsevier B.V. All rights reserved.

Social in, social out: How the brain responds to social language with more social language

PubMed Central

O’Donnell, Matthew Brook; Falk, Emily B.; Lieberman, Matthew D.

2014-01-01

Social connection is a fundamental human need. As such, people’s brains are sensitized to social cues, such as those carried by language, and to promoting social communication. The neural mechanisms of certain key building blocks in this process, such as receptivity to and reproduction of social language, however, are not known. We combined quantitative linguistic analysis and neuroimaging to connect neural activity in brain regions used to simulate the mental states of others with exposure to, and re-transmission of, social language. Our results link findings on successful idea transmission from communication science, sociolinguistics and cognitive neuroscience to prospectively predict the degree of social language that participants utilize when re-transmitting ideas as a function of 1) initial language inputs and 2) neural activity during idea exposure. PMID:27642220

Contributions of episodic retrieval and mentalizing to autobiographical thought: evidence from functional neuroimaging, resting-state connectivity, and fMRI meta-analyses.

PubMed

Andrews-Hanna, Jessica R; Saxe, Rebecca; Yarkoni, Tal

2014-05-01

A growing number of studies suggest the brain's "default network" becomes engaged when individuals recall their personal past or simulate their future. Recent reports of heterogeneity within the network raise the possibility that these autobiographical processes comprised of multiple component processes, each supported by distinct functional-anatomic subsystems. We previously hypothesized that a medial temporal subsystem contributes to autobiographical memory and future thought by enabling individuals to retrieve prior information and bind this information into a mental scene. Conversely, a dorsal medial subsystem was proposed to support social-reflective aspects of autobiographical thought, allowing individuals to reflect on the mental states of one's self and others (i.e. "mentalizing"). To test these hypotheses, we first examined activity in the default network subsystems as participants performed two commonly employed tasks of episodic retrieval and mentalizing. In a subset of participants, relationships among task-evoked regions were examined at rest, in the absence of an overt task. Finally, large-scale fMRI meta-analyses were conducted to identify brain regions that most strongly predicted the presence of episodic retrieval and mentalizing, and these results were compared to meta-analyses of autobiographical tasks. Across studies, laboratory-based episodic retrieval tasks were preferentially linked to the medial temporal subsystem, while mentalizing tasks were preferentially linked to the dorsal medial subsystem. In turn, autobiographical tasks engaged aspects of both subsystems. These results suggest the default network is a heterogeneous brain system whose subsystems support distinct component processes of autobiographical thought. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

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

PubMed

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

2016-01-01

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

Critical brain circuits at the intersection between stress and learning.

PubMed

Bangasser, Debra A; Shors, Tracey J

2010-07-01

The effects of stressful life experience on learning are pervasive and vary greatly both within and between individuals. It is therefore unlikely that any one mechanism will underlie these complicated processes. Nonetheless, without identifying the necessary and sufficient circuitry, no complete mechanism or set of mechanisms can be identified. In this review, we provide two anatomical frameworks through which stressful life experience can influence processes related to learning and memory. In the first, stressful experience releases stress hormones, primarily from the adrenals, which directly impact brain areas engaged in learning. In the second, stressful experience indirectly alters the circuits used in learning via intermediary brain regions. Importantly, these intermediary brain regions are not integral to the stress response or learning itself, but rather link the consequences of a stressful experience with circuits used to learn associations. As reviewed, the existing literature provides support for both frameworks, with somewhat more support for the first but sufficient evidence for the latter which involves intermediary structures. Once we determine the circumstances that engage each framework and identify which one is most predominant, we can begin to focus our efforts on describing the neuronal and hormonal mechanisms that operate within these circuits to influence cognitive processes after stressful life experience.

Salience network and olanzapine in schizophrenia: implications for treatment in anorexia nervosa.

PubMed

Stip, Emmanuel; Lungu, Ovidiu V

2015-03-01

The salience network (SN), a set of brain regions composed of the anterior fronto-insular cortex (aFI) and the anterior cingulate cortex (ACC), is usually involved in interoception, self-regulating, and action selection. Accumulating evidence indicates that dysfunctions in this network are associated with various pathophysiological deficits in both schizophrenia and eating disorders, stemming mainly from dysfunctional information processing of internal or external stimuli. In addition, the metabolic side effects of some antipsychotics (APs), as well as their pharmacological mechanisms of action, also suggest a link between the functional and neurophysiological changes in the brain in both schizophrenia and in eating disorders. Nevertheless, there is still a knowledge gap in explicitly and directly linking the metabolic side effects associated with AP treatment with the dysfunction in SN associated with processing of food-related information in schizophrenia. Here we provide neuroimaging evidence for such a link, by presenting data on a group of schizophrenia patients who followed 16 weeks of olanzapine treatment and undertook a passive viewing task while their brain activity was recorded. In response to food-related dynamic stimuli (video clips), we observed a decreased activity in SN (aFI and ACC) after the treatment, which also correlated with ghrelin plasma concentration and a measure of dietary restraint. Taken together with past findings regarding the role of SN in both schizophrenia and eating disorders, our results suggest that enhancing the reactivity in the SN has the potential to be a treatment strategy in people with anorexia nervosa. NCT 00290121.

Age-dependent and -independent changes in attention-deficit/hyperactivity disorder (ADHD) during spatial working memory performance.

PubMed

Bollmann, Steffen; Ghisleni, Carmen; Poil, Simon-Shlomo; Martin, Ernst; Ball, Juliane; Eich-Höchli, Dominique; Klaver, Peter; O'Gorman, Ruth L; Michels, Lars; Brandeis, Daniel

2017-06-01

Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.

Neuronal Correlates of Individual Differences in the Big Five Personality Traits: Evidences from Cortical Morphology and Functional Homogeneity.

PubMed

Li, Ting; Yan, Xu; Li, Yuan; Wang, Junjie; Li, Qiang; Li, Hong; Li, Junfeng

2017-01-01

There have been many neuroimaging studies of human personality traits, and it have already provided glimpse into the neurobiology of complex traits. And most of previous studies adopt voxel-based morphology (VBM) analysis to explore the brain-personality mechanism from two levels (vertex and regional based), the findings are mixed with great inconsistencies and the brain-personality relations are far from a full understanding. Here, we used a new method of surface-based morphology (SBM) analysis, which provides better alignment of cortical landmarks to generate about the associations between cortical morphology and the personality traits across 120 healthy individuals at both vertex and regional levels. While to further reveal local functional correlates of the morphology-personality relationships, we related surface-based functional homogeneity measures to the regions identified in the regional-based SBM correlation. Vertex-wise analysis revealed that people with high agreeableness exhibited larger areas in the left superior temporal gyrus. Based on regional parcellation we found that extroversion was negatively related with the volume of the left lateral occipito-temporal gyrus and agreeableness was negatively associated with the sulcus depth of the left superior parietal lobule. Moreover, increased regional homogeneity in the left lateral occipito-temporal gyrus is related to the scores of extroversion, and increased regional homogeneity in the left superior parietal lobule is related to the scores of agreeableness. These findings provide supporting evidence of a link between personality and brain structural mysteries with a method of SBM, and further suggest that local functional homogeneity of personality traits has neurobiological relevance that is likely based on anatomical substrates.

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue.

PubMed

Devall, Matthew; Smith, Rebecca G; Jeffries, Aaron; Hannon, Eilis; Davies, Matthew N; Schalkwyk, Leonard; Mill, Jonathan; Weedon, Michael; Lunnon, Katie

2017-01-01

DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions ( p  < 0.05) in the mitochondrial genome, between anatomically separate cortical regions and the cerebellum in matched samples ( N  = 3 matched donors). Further analysis identified eight significant differentially methylated regions between the total cortex and cerebellum after correcting for multiple testing. Using unsupervised hierarchical clustering analysis of the mitochondrial DNA methylome, we were able to identify tissue-specific patterns of mitochondrial DNA methylation between blood, cerebellum and cortex. Our study represents a comprehensive analysis of the mitochondrial methylome using pre-existing Methylated DNA Immunoprecipitation Sequencing data to identify brain region-specific patterns of mitochondrial DNA methylation.

Genetics of Cerebellar and Neocortical Expansion in Anthropoid Primates: A Comparative Approach

PubMed Central

Harrison, Peter W.; Montgomery, Stephen H.

2017-01-01

What adaptive changes in brain structure and function underpin the evolution of increased cognitive performance in humans and our close relatives? Identifying the genetic basis of brain evolution has become a major tool in answering this question. Numerous cases of positive selection, altered gene expression or gene duplication have been identified that may contribute to the evolution of the neocortex, which is widely assumed to play a predominant role in cognitive evolution. However, the components of the neocortex co-evolve with other functionally interdependent regions of the brain, most notably in the cerebellum. The cerebellum is linked to a range of cognitive tasks and expanded rapidly during hominoid evolution. Here we present data that suggest that, across anthropoid primates, protein-coding genes with known roles in cerebellum development were just as likely to be targeted by selection as genes linked to cortical development. Indeed, based on currently available gene ontology data, protein-coding genes with known roles in cerebellum development are more likely to have evolved adaptively during hominoid evolution. This is consistent with phenotypic data suggesting an accelerated rate of cerebellar expansion in apes that is beyond that predicted from scaling with the neocortex in other primates. Finally, we present evidence that the strength of selection on specific genes is associated with variation in the volume of either the neocortex or the cerebellum, but not both. This result provides preliminary evidence that co-variation between these brain components during anthropoid evolution may be at least partly regulated by selection on independent loci, a conclusion that is consistent with recent intraspecific genetic analyses and a mosaic model of brain evolution that predicts adaptive evolution of brain structure. PMID:28683440

Hybrid ICA-Bayesian network approach reveals distinct effective connectivity differences in schizophrenia.

PubMed

Kim, D; Burge, J; Lane, T; Pearlson, G D; Kiehl, K A; Calhoun, V D

2008-10-01

We utilized a discrete dynamic Bayesian network (dDBN) approach (Burge, J., Lane, T., Link, H., Qiu, S., Clark, V.P., 2007. Discrete dynamic Bayesian network analysis of fMRI data. Hum Brain Mapp.) to determine differences in brain regions between patients with schizophrenia and healthy controls on a measure of effective connectivity, termed the approximate conditional likelihood score (ACL) (Burge, J., Lane, T., 2005. Learning Class-Discriminative Dynamic Bayesian Networks. Proceedings of the International Conference on Machine Learning, Bonn, Germany, pp. 97-104.). The ACL score represents a class-discriminative measure of effective connectivity by measuring the relative likelihood of the correlation between brain regions in one group versus another. The algorithm is capable of finding non-linear relationships between brain regions because it uses discrete rather than continuous values and attempts to model temporal relationships with a first-order Markov and stationary assumption constraint (Papoulis, A., 1991. Probability, random variables, and stochastic processes. McGraw-Hill, New York.). Since Bayesian networks are overly sensitive to noisy data, we introduced an independent component analysis (ICA) filtering approach that attempted to reduce the noise found in fMRI data by unmixing the raw datasets into a set of independent spatial component maps. Components that represented noise were removed and the remaining components reconstructed into the dimensions of the original fMRI datasets. We applied the dDBN algorithm to a group of 35 patients with schizophrenia and 35 matched healthy controls using an ICA filtered and unfiltered approach. We determined that filtering the data significantly improved the magnitude of the ACL score. Patients showed the greatest ACL scores in several regions, most markedly the cerebellar vermis and hemispheres. Our findings suggest that schizophrenia patients exhibit weaker connectivity than healthy controls in multiple regions, including bilateral temporal, frontal, and cerebellar regions during an auditory paradigm.

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

The role of the posterior cingulate cortex in cognition and disease

PubMed Central

Sharp, David J.

2014-01-01

The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time. PMID:23869106

Neuropathology of alcoholism.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

Chronic alcohol consumption results in structural changes to the brain. In alcoholics without coexisting thiamine deficiency or liver disease this is largely restricted to a loss of white-matter volume. When it occurs, neuronal loss is limited in anatomic distribution and only detected with quantitative techniques. This relative paucity of neurodegeneration is reflected in studies of gene and protein expression in postmortem brain where findings are subtle and discordant between studies. In alcoholics with coexisting pathologies, neuronal loss is more marked and affects a wider range of anatomic regions, especially subcortical nuclei. Although this more widespread damage may reflect a more severe drinking history, there is evidence linking thiamine deficiency and the consequences of liver disease to the pathogenesis of alcohol-related brain damage. Furthermore, a range of other factors, such as cigarette smoking and mood disorders, that are common in alcoholics, have the potential to influence studies of brain pathology and should be considered in further studies of the neuropathology of alcoholism. © 2014 Elsevier B.V. All rights reserved.

Can a few non‐coding mutations make a human brain?

PubMed Central

Franchini, Lucía F.

2015-01-01

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. Also watch the Video Abstract. PMID:26350501

Perceived quality of maternal care in childhood and structure and function of mothers’ brain

PubMed Central

Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Newman, Michal-Ann; Feldman, Ruth; Swain, James E.

2014-01-01

Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers. PMID:20590729

Mapping higher-order relations between brain structure and function with embedded vector representations of connectomes.

PubMed

Rosenthal, Gideon; Váša, František; Griffa, Alessandra; Hagmann, Patric; Amico, Enrico; Goñi, Joaquín; Avidan, Galia; Sporns, Olaf

2018-06-05

Connectomics generates comprehensive maps of brain networks, represented as nodes and their pairwise connections. The functional roles of nodes are defined by their direct and indirect connectivity with the rest of the network. However, the network context is not directly accessible at the level of individual nodes. Similar problems in language processing have been addressed with algorithms such as word2vec that create embeddings of words and their relations in a meaningful low-dimensional vector space. Here we apply this approach to create embedded vector representations of brain networks or connectome embeddings (CE). CE can characterize correspondence relations among brain regions, and can be used to infer links that are lacking from the original structural diffusion imaging, e.g., inter-hemispheric homotopic connections. Moreover, we construct predictive deep models of functional and structural connectivity, and simulate network-wide lesion effects using the face processing system as our application domain. We suggest that CE offers a novel approach to revealing relations between connectome structure and function.

Longitudinal brain MRI study in a mouse model of Rett Syndrome and the effects of choline.

PubMed

Ward, B C; Agarwal, S; Wang, K; Berger-Sweeney, J; Kolodny, N H

2008-07-01

Rett Syndrome (RTT), the second most common cause of mental retardation in girls, is associated with mutations of an X-linked gene encoding the transcriptional repressor protein MeCP2. Mecp2(1lox) mutant mice express no functional MeCP2 protein and exhibit behavioral abnormalities similar to those seen in RTT patients. Here we monitor the development of both whole brain and regional volumes between 21 and 42 days of age in this model of RTT using MRI. We see decreases in whole brain volumes in both male and female mutant mice. Cerebellar and ventricular volumes are also decreased in RTT males. Previous work has suggested that perinatal choline supplementation alleviates some of the behavioral deficits in both male and female Mecp2(1lox) mutant mice. Here we show that perinatal choline supplementation also positively affects whole brain volume in heterozygous females, and cerebellar volume in male RTT mice.

Increased Sleep Depth in Developing Neural Networks: New Insights from Sleep Restriction in Children

PubMed Central

Kurth, Salome; Dean, Douglas C.; Achermann, Peter; O’Muircheartaigh, Jonathan; Huber, Reto; Deoni, Sean C. L.; LeBourgeois, Monique K.

2016-01-01

Brain networks respond to sleep deprivation or restriction with increased sleep depth, which is quantified as slow-wave activity (SWA) in the sleep electroencephalogram (EEG). When adults are sleep deprived, this homeostatic response is most pronounced over prefrontal brain regions. However, it is unknown how children’s developing brain networks respond to acute sleep restriction, and whether this response is linked to myelination, an ongoing process in childhood that is critical for brain development and cortical integration. We implemented a bedtime delay protocol in 5- to 12-year-old children to obtain partial sleep restriction (1-night; 50% of their habitual sleep). High-density sleep EEG was assessed during habitual and restricted sleep and brain myelin content was obtained using mcDESPOT magnetic resonance imaging. The effect of sleep restriction was analyzed using statistical non-parametric mapping with supra-threshold cluster analysis. We observed a localized homeostatic SWA response following sleep restriction in a specific parieto-occipital region. The restricted/habitual SWA ratio was negatively associated with myelin water fraction in the optic radiation, a developing fiber bundle. This relationship occurred bilaterally over parieto-temporal areas and was adjacent to, but did not overlap with the parieto-occipital region showing the most pronounced homeostatic SWA response. These results provide evidence for increased sleep need in posterior neural networks in children. Sleep need in parieto-temporal areas is related to myelin content, yet it remains speculative whether age-related myelin growth drives the fading of the posterior homeostatic SWA response during the transition to adulthood. Whether chronic insufficient sleep in the sensitive period of early life alters the anatomical generators of deep sleep slow-waves is an important unanswered question. PMID:27708567

Multifaceted Genomic Risk for Brain Function in Schizophrenia

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Pearlson, Godfrey D.; Ehrlich, Stefan; Turner, Jessica A.; Ho, Beng-Choon; Wassink, Thomas H.; Michael, Andrew M; Liu, Jingyu

2012-01-01

Recently, deriving candidate endophenotypes from brain imaging data has become a valuable approach to study genetic influences on schizophrenia (SZ), whose pathophysiology remains unclear. In this work we utilized a multivariate approach, parallel independent component analysis, to identify genomic risk components associated with brain function abnormalities in SZ. 5157 candidate single nucleotide polymorphisms (SNPs) were derived from genome-wide array based on their possible connections with SZ and further investigated for their associations with brain activations captured with functional magnetic resonance imaging (fMRI) during a sensorimotor task. Using data from 92 SZ patients and 116 healthy controls, we detected a significant correlation (r= 0.29; p= 2.41×10−5) between one fMRI component and one SNP component, both of which significantly differentiated patients from controls. The fMRI component mainly consisted of precentral and postcentral gyri, the major activated regions in the motor task. On average, higher activation in these regions was observed in participants with higher loadings of the linked SNP component, predominantly contributed to by 253 SNPs. 138 identified SNPs were from known coding regions of 100 unique genes. 31 identified SNPs did not differ between groups, but moderately correlated with some other group-discriminating SNPs, indicating interactions among alleles contributing towards elevated SZ susceptibility. The genes associated with the identified SNPs participated in four neurotransmitter pathways: GABA receptor signaling, dopamine receptor signaling, neuregulin signaling and glutamate receptor signaling. In summary, our work provides further evidence for the complexity of genomic risk to the functional brain abnormality in SZ and suggests a pathological role of interactions between SNPs, genes and multiple neurotransmitter pathways. PMID:22440650

Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

PubMed

Plessow, Franziska; Marengi, Dean A; Perry, Sylvia K; Felicione, Julia M; Franklin, Rachel; Holmes, Tara M; Holsen, Laura M; Makris, Nikolaos; Deckersbach, Thilo; Lawson, Elizabeth A

2018-02-01

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

Preserved Haptic Shape Processing after Bilateral LOC Lesions.

PubMed

Snow, Jacqueline C; Goodale, Melvyn A; Culham, Jody C

2015-10-07

The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.'s psychophysical response profile to haptically explored shapes was also indistinguishable from controls. Using fMRI, M.C. showed no object-selective visual or haptic responses in LOC, but her pattern of haptic activation in other brain regions was remarkably similar to healthy controls. Although LOC is routinely active during visual and haptic shape recognition tasks, it is not essential for haptic recognition of object shape. The lateral occipital complex (LOC) is a brain region regarded to be critical for recognizing object shape, both in vision and in touch. However, causal evidence linking LOC with haptic shape processing is lacking. We studied recognition performance, psychophysical sensitivity, and brain response to touched objects, in a patient (M.C.) with extensive lesions involving LOC bilaterally. Despite being severely impaired in visual shape recognition, M.C. was able to identify objects via touch and she showed normal sensitivity to a haptic shape illusion. M.C.'s brain response to touched objects in areas of undamaged cortex was also very similar to that observed in neurologically healthy controls. These results demonstrate that LOC is not necessary for recognizing objects via touch. Copyright © 2015 the authors 0270-6474/15/3513745-16$15.00/0.

HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy.

PubMed

Kallianpur, Kalpana J; Valcour, Victor G; Lerdlum, Sukalaya; Busovaca, Edgar; Agsalda, Melissa; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L K; Tipsuk, Somporn; Shikuma, Cecilia M; Shiramizu, Bruce T; Ananworanich, Jintanat

2014-07-17

To examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART). A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion. CD14 cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA). We studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/μl and log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells for this cohort, a threshold value above which CD14 HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14 HIV DNA  ≥ 45 copies/10 cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4 cell count and intracranial volume. HIV DNA burden in CD14 monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells.

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

PubMed

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

2018-06-01

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

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

PubMed

Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

2015-08-01

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Regional Homogeneity

PubMed Central

Jiang, Lili; Zuo, Xi-Nian

2015-01-01

Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004

Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring.

PubMed

Rudolph, Marc D; Graham, Alice M; Feczko, Eric; Miranda-Dominguez, Oscar; Rasmussen, Jerod M; Nardos, Rahel; Entringer, Sonja; Wadhwa, Pathik D; Buss, Claudia; Fair, Damien A

2018-05-01

Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma interleukin-6 (IL-6) concentrations, for large-scale brain system development and emerging executive function skills in offspring. We assessed maternal IL-6 during pregnancy, functional magnetic resonance imaging acquired in neonates, and working memory (an important component of executive function) at 2 years of age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap substantially with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at 2 years of age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function.

Apollo’s gift: new aspects of neurologic music therapy

PubMed Central

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

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.

Spectral mapping of brain functional connectivity from diffusion imaging.

PubMed

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

2018-01-23

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

Apollo's gift: new aspects of neurologic music therapy.

PubMed

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

PubMed

Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

2016-04-01

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Association of ventral striatum monoamine oxidase-A binding and functional connectivity in antisocial personality disorder with high impulsivity: A positron emission tomography and functional magnetic resonance imaging study.

PubMed

Kolla, Nathan J; Dunlop, Katharine; Downar, Jonathan; Links, Paul; Bagby, R Michael; Wilson, Alan A; Houle, Sylvain; Rasquinha, Fawn; Simpson, Alexander I; Meyer, Jeffrey H

2016-04-01

Impulsivity is a core feature of antisocial personality disorder (ASPD) associated with abnormal brain function and neurochemical alterations. The ventral striatum (VS) is a key region of the neural circuitry mediating impulsive behavior, and low monoamine oxidase-A (MAO-A) level in the VS has shown a specific relationship to the impulsivity of ASPD. Because it is currently unknown whether phenotypic MAO-A markers can influence brain function in ASPD, we investigated VS MAO-A level and the functional connectivity (FC) of two seed regions, superior and inferior VS (VSs, VSi). Nineteen impulsive ASPD males underwent [(11)C] harmine positron emission tomography scanning to measure VS MAO-A VT, an index of MAO-A density, and resting-state functional magnetic resonance imaging that assessed the FC of bilateral seed regions in the VSi and VSs. Subjects also completed self-report impulsivity measures. Results revealed functional coupling of the VSs with bilateral dorsomedial prefrontal cortex (DMPFC) that was correlated with VS MAO-A VT (r=0.47, p=0.04), and functional coupling of the VSi with right hippocampus that was anti-correlated with VS MAO-A VT (r=-0.55, p=0.01). Additionally, VSs-DMPFC FC was negatively correlated with NEO Personality Inventory-Revised impulsivity (r=-0.49, p=0.03), as was VSi-hippocampus FC with Barratt Impulsiveness Scale-11 motor impulsiveness (r=-0.50, p=0.03). These preliminary results highlight an association of VS MAO-A level with the FC of striatal regions linked to impulsive behavior in ASPD and suggest that phenotype-based brain markers of ASPD have relevance to understanding brain function. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

PubMed Central

Ryan, Nicholas P.; Catroppa, Cathy; Beare, Richard; Silk, Timothy J.; Crossley, Louise; Beauchamp, Miriam H.; Yeates, Keith Owen; Anderson, Vicki A.

2016-01-01

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the ‘social brain network’ (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2–8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.

PubMed

Lutkenhoff, Evan S; Chiang, Jeffrey; Tshibanda, Luaba; Kamau, Evelyn; Kirsch, Murielle; Pickard, John D; Laureys, Steven; Owen, Adrian M; Monti, Martin M

2015-07-01

What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal. © 2015 American Neurological Association.

Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.

PubMed

Shahid, Hinna; Sebastian, Rajani; Tippett, Donna C; Saxena, Sadhvi; Wright, Amy; Hanayik, Taylor; Breining, Bonnie; Bonilha, Leonardo; Fridriksson, Julius; Rorden, Chris; Hillis, Argye E

2018-02-01

Here we illustrate how investigation of individuals acutely after stroke, before structure/function reorganization through recovery or rehabilitation, can be helpful in answering questions about the role of specific brain regions in language functions. Although there is converging evidence from a variety of sources that the left posterior-superior temporal gyrus plays some role in spoken word comprehension, its precise role in this function has not been established. We hypothesized that this region is essential for distinguishing between semantically related words, because it is critical for linking the spoken word to the complete semantic representation. We tested this hypothesis in 127 individuals with 48 hours of acute ischemic stroke, before the opportunity for reorganization or recovery. We identified tissue dysfunction (acute infarct and/or hypoperfusion) in gray and white matter parcels of the left hemisphere, and we evaluated the association between rate of semantic errors in a word-picture verification tasks and extent of tissue dysfunction in each region. We found that after correcting for lesion volume and multiple comparisons, the rate of semantic errors correlated with the extent of tissue dysfunction in left posterior-superior temporal gyrus and retrolenticular white matter. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Emotion Awareness Predicts Body Mass Index Percentile Trajectories in Youth.

PubMed

Whalen, Diana J; Belden, Andy C; Barch, Deanna; Luby, Joan

2015-10-01

To examine the rate of change in body mass index (BMI) percentile across 3 years in relation to emotion identification ability and brain-based reactivity in emotional processing regions. A longitudinal sample of 202 youths completed 3 functional magnetic resonance imaging-based facial processing tasks and behavioral emotion differentiation tasks. We examined the rate of change in the youth's BMI percentile as a function of reactivity in emotional processing brain regions and behavioral emotion identification tasks using multilevel modeling. Lower correct identification of both happiness and sadness measured behaviorally predicted increases in BMI percentile across development, whereas higher correct identification of both happiness and sadness predicted decreases in BMI percentile, while controlling for children's pubertal status, sex, ethnicity, IQ score, exposure to antipsychotic medication, family income-to-needs ratio, and externalizing, internalizing, and depressive symptoms. Greater neural activation in emotional reactivity regions to sad faces also predicted increases in BMI percentile during development, also controlling for the aforementioned covariates. Our findings provide longitudinal developmental data demonstrating links between both emotion identification ability and greater neural reactivity in emotional processing regions with trajectories of BMI percentiles across childhood. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional overlap between regions involved in speech perception and in monitoring one's own voice during speech production.

PubMed

Zheng, Zane Z; Munhall, Kevin G; Johnsrude, Ingrid S

2010-08-01

The fluency and the reliability of speech production suggest a mechanism that links motor commands and sensory feedback. Here, we examined the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or not and by examining the overlap with the network recruited during passive listening to speech sounds. We used real-time signal processing to compare brain activity when participants whispered a consonant-vowel-consonant word ("Ted") and either heard this clearly or heard voice-gated masking noise. We compared this to when they listened to yoked stimuli (identical recordings of "Ted" or noise) without speaking. Activity along the STS and superior temporal gyrus bilaterally was significantly greater if the auditory stimulus was (a) processed as the auditory concomitant of speaking and (b) did not match the predicted outcome (noise). The network exhibiting this Feedback Type x Production/Perception interaction includes a superior temporal gyrus/middle temporal gyrus region that is activated more when listening to speech than to noise. This is consistent with speech production and speech perception being linked in a control system that predicts the sensory outcome of speech acts and that processes an error signal in speech-sensitive regions when this and the sensory data do not match.

Functional overlap between regions involved in speech perception and in monitoring one’s own voice during speech production

PubMed Central

Zheng, Zane Z.; Munhall, Kevin G; Johnsrude, Ingrid S

2009-01-01

The fluency and reliability of speech production suggests a mechanism that links motor commands and sensory feedback. Here, we examine the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or not, and examining the overlap with the network recruited during passive listening to speech sounds. We use real-time signal processing to compare brain activity when participants whispered a consonant-vowel-consonant word (‘Ted’) and either heard this clearly, or heard voice-gated masking noise. We compare this to when they listened to yoked stimuli (identical recordings of ‘Ted’ or noise) without speaking. Activity along the superior temporal sulcus (STS) and superior temporal gyrus (STG) bilaterally was significantly greater if the auditory stimulus was a) processed as the auditory concomitant of speaking and b) did not match the predicted outcome (noise). The network exhibiting this Feedback type by Production/Perception interaction includes an STG/MTG region that is activated more when listening to speech than to noise. This is consistent with speech production and speech perception being linked in a control system that predicts the sensory outcome of speech acts, and that processes an error signal in speech-sensitive regions when this and the sensory data do not match. PMID:19642886

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

PubMed

Piwecka, Monika; Glažar, Petar; Hernandez-Miranda, Luis R; Memczak, Sebastian; Wolf, Susanne A; Rybak-Wolf, Agnieszka; Filipchyk, Andrei; Klironomos, Filippos; Cerda Jara, Cledi Alicia; Fenske, Pascal; Trimbuch, Thorsten; Zywitza, Vera; Plass, Mireya; Schreyer, Luisa; Ayoub, Salah; Kocks, Christine; Kühn, Ralf; Rosenmund, Christian; Birchmeier, Carmen; Rajewsky, Nikolaus

2017-09-22

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos , a direct miR-7 target, was enhanced in Cdr1as -deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Event-Related Oscillations in Alcoholism Research: A Review

PubMed Central

Pandey, Ashwini K; Kamarajan, Chella; Rangaswamy, Madhavi; Porjesz, Bernice

2013-01-01

Alcohol dependence is characterized as a multi-factorial disorder caused by a complex interaction between genetic and environmental liabilities across development. A variety of neurocognitive deficits/dysfunctions involving impairments in different brain regions and/or neural circuitries have been associated with chronic alcoholism, as well as with a predisposition to develop alcoholism. Several neurobiological and neurobehavioral approaches and methods of analyses have been used to understand the nature of these neurocognitive impairments/deficits in alcoholism. In the present review, we have examined relatively novel methods of analyses of the brain signals that are collectively referred to as event-related oscillations (EROs) and show promise to further our understanding of human brain dynamics while performing various tasks. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying responses to sensory and cognitive events, thus providing a closer link to the physiology underlying them. Here, we have reviewed EROs in the study of alcoholism, their usefulness in understanding dynamical brain functions/dysfunctions associated with alcoholism as well as their utility as effective endophenotypes to identify and understand genes associated with both brain oscillations and alcoholism. PMID:24273686

Age-Related Impairments in Object-Place Associations Are Not Due to Hippocampal Dysfunction

PubMed Central

Hernandez, Abigail R.; Maurer, Andrew P.; Reasor, Jordan E.; Turner, Sean M.; Barthle, Sarah E.; Johnson, Sarah A.; Burke, Sara N.

2016-01-01

Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly. PMID:26413723

Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

PubMed Central

Slotkin, Theodore A.; Seidler, Frederic J.; Fumagalli, Fabio

2007-01-01

Background The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. Objectives We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1–4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon. Methods Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem. Results Chlorpyrifos and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgf22. However, they differed in that the effects on fgf2 and fgfr4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1. Conclusions The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoxicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcomes. PMID:17589599

Subcortical shape and volume abnormalities in an elderly HIV+ cohort

NASA Astrophysics Data System (ADS)

Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

2015-03-01

Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

PubMed

Lambert, Christian; Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

2016-04-01

Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Identification of neural circuits involved in female genital responses in the rat: A dual virus and anterograde tracing study

PubMed Central

Marson, L.; Murphy, A Z

2010-01-01

The spinal and peripheral innervation of the clitoris and vagina are fairly well understood. However, little is known regarding supraspinal control of these pelvic structures. The multisynaptic tracer pseudorabies virus (PRV) was used to map the brain neurons that innervate the clitoris and vagina. In order to delineate forebrain input onto PRV labeled cells, the anterograde tracer biotinylated dextran amine (BDA) was injected into the medial preoptic nucleus (MPO), ventromedial nucleus of the hypothalamus (VMN) or the midbrain periaqueductal gray (PAG) 10 days prior to viral injections. These brain regions have been intimately linked to various aspects of female reproductive behavior. Four days after viral injections, into the vagina and clitoris PRV labeled cells were observed in the paraventricular nucleus, Barrington’s nucleus, the A5 region, and the nucleus paragigantocellularis. At 5 days post-viral administration, additional PRV labeled cells were observed within the preoptic region, VMN, PAG and lateral hypothalamus. Anterograde labeling from the MPO terminated among PRV positive cells primarily within the dorsal paraventricular nucleus of the hypothalamus (PVN), ventrolateral VMN (VMNvl), caudal PAG and nucleus paragigantocellularis (nPGi). Anterograde labeling from the VMN terminated among PRV positive cells in the MPO and lateral/ventrolateral PAG. Anterograde labeling from the PAG terminated among PRV positive cells in the PVN, ventral hypothalamus and nPGi. Transynaptically labeled cells in the lateral hypothalamus, Barrington's nucleus and ventromedial medulla received innervation from all three sources. These studies, together, identify several CNS sites participating in the neural control of female sexual responses. They also provide the first data demonstrating a link between the MPO, VMNvl and PAG and CNS regions innervating the clitoris and vagina, providing support that these areas play a major role in female genital responses. PMID:16914428

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed Central

Čeko, Marta; Gracely, John L.; Fitzcharles, Mary-Ann; Seminowicz, David A.; Schweinhardt, Petra

2015-01-01

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or “negative” [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. SIGNIFICANCE STATEMENT We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks [“external-task positive” and “default-mode network” (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. PMID:26290236

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed

Čeko, Marta; Gracely, John L; Fitzcharles, Mary-Ann; Seminowicz, David A; Schweinhardt, Petra; Bushnell, M Catherine

2015-08-19

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or "negative" [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks ["external-task positive" and "default-mode network" (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. Copyright © 2015 the authors 0270-6474/15/3511596-11$15.00/0.

Sex-specific effects of cytotoxic chemotherapy agents cyclophospha-mide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus – an aging connection

PubMed Central

Kovalchuk, Anna; Rodriguez-Juarez, Rocio; Ilnytskyy, Yaroslav; Byeon, Boseon; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis. PMID:27032448

Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease: a meta-analysis of 75 fMRI studies.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; He, Yong; Zuo, Xi-Nian

2015-03-01

Most of the previous task functional magnetic resonance imaging (fMRI) studies found abnormalities in distributed brain regions in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and few studies investigated the brain network dysfunction from the system level. In this meta-analysis, we aimed to examine brain network dysfunction in MCI and AD. We systematically searched task-based fMRI studies in MCI and AD published between January 1990 and January 2014. Activation likelihood estimation meta-analyses were conducted to compare the significant group differences in brain activation, the significant voxels were overlaid onto seven referenced neuronal cortical networks derived from the resting-state fMRI data of 1,000 healthy participants. Thirty-nine task-based fMRI studies (697 MCI patients and 628 healthy controls) were included in MCI-related meta-analysis while 36 task-based fMRI studies (421 AD patients and 512 healthy controls) were included in AD-related meta-analysis. The meta-analytic results revealed that MCI and AD showed abnormal regional brain activation as well as large-scale brain networks. MCI patients showed hypoactivation in default, frontoparietal, and visual networks relative to healthy controls, whereas AD-related hypoactivation mainly located in visual, default, and ventral attention networks relative to healthy controls. Both MCI-related and AD-related hyperactivation fell in frontoparietal, ventral attention, default, and somatomotor networks relative to healthy controls. MCI and AD presented different pathological while shared similar compensatory large-scale networks in fulfilling the cognitive tasks. These system-level findings are helpful to link the fundamental declines of cognitive tasks to brain networks in MCI and AD. © 2014 Wiley Periodicals, Inc.

Distribution of cellular HSV-1 receptor expression in human brain.

PubMed

Lathe, Richard; Haas, Juergen G

2017-06-01

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.

The Anatomical and Evolutionary Relationship between Self-awareness and Theory of Mind.

PubMed

Guise, Kevin; Kelly, Karen; Romanowski, Jennifer; Vogeley, Kai; Platek, Steven M; Murray, Elizabeth; Keenan, Julian Paul

2007-06-01

Although theories that examine direct links between behavior and brain remain incomplete, it is known that brain expansion significantly correlates with caloric and oxygen demands. Therefore, one of the principles governing evolutionary cognitive neuroscience is that cognitive abilities that require significant brain function (and/or structural support) must be accompanied by significant fitness benefit to offset the increased metabolic demands. One such capacity is self-awareness (SA), which (1) is found only in the greater apes and (2) remains unclear in terms of both cortical underpinning and possible fitness benefit. In the current experiment, transcranial magnetic stimulation (TMS) was applied to the prefrontal cortex during a spatial perspective-taking task involving self and other viewpoints. It was found that delivery of TMS to the right prefrontal region disrupted self-, but not other-, perspective. These data suggest that self-awareness may have evolved in concert with other right hemisphere cognitive abilities.

The role of symmetry in the regulation of brain dynamics

NASA Astrophysics Data System (ADS)

Tang, Evelyn; Giusti, Chad; Cieslak, Matthew; Grafton, Scott; Bassett, Danielle

Synchronous neural processes regulate a wide range of behaviors from attention to learning. Yet structural constraints on these processes are far from understood. We draw on new theoretical links between structural symmetries and the control of synchronous function, to offer a reconceptualization of the relationships between brain structure and function in human and non-human primates. By classifying 3-node motifs in macaque connectivity data, we find the most prevalent motifs can theoretically ensure a diversity of function including strict synchrony as well as control to arbitrary states. The least prevalent motifs are theoretically controllable to arbitrary states, which may not be desirable in a biological system. In humans, regions with high topological similarity of connections (a continuous notion related to symmetry) are most commonly found in fronto-parietal systems, which may account for their critical role in cognitive control. Collectively, our work underscores the role of symmetry and topological similarity in regulating dynamics of brain function.

Functional brain imaging predicts public health campaign success

PubMed Central

O’Donnell, Matthew Brook; Tompson, Steven; Gonzalez, Richard; Dal Cin, Sonya; Strecher, Victor; Cummings, Kenneth Michael; An, Lawrence

2016-01-01

Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a ‘self-localizer’ defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400 000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R2 up to 0.65) and (ii) this relationship depends on message content—self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns. PMID:26400858

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

PubMed

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

2018-06-01

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

Gene regulatory network analysis reveals differences in site-specific cell fate determination in mammalian brain

PubMed Central

Ertaylan, Gökhan; Okawa, Satoshi; Schwamborn, Jens C.; del Sol, Antonio

2014-01-01

Neurogenesis—the generation of new neurons—is an ongoing process that persists in the adult mammalian brain of several species, including humans. In this work we analyze two discrete brain regions: the subventricular zone (SVZ) lining the walls of the lateral ventricles; and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus in mice and shed light on the SVZ and SGZ specific neurogenesis. We propose a computational model that relies on the construction and analysis of region specific gene regulatory networks (GRNs) from the publicly available data on these two regions. Using this model a number of putative factors involved in neuronal stem cell (NSC) identity and maintenance were identified. We also demonstrate potential gender and niche-derived differences based on cell surface and nuclear receptors via Ar, Hif1a, and Nr3c1. We have also conducted cell fate determinant analysis for SVZ NSC populations to Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the Granular Cell Layer. We report 31 candidate cell fate determinant gene pairs, ready to be validated. We focus on Ar—Pax6 in SVZ and Sox2—Ncor1 in SGZ. Both pairs are expressed and localized in the suggested anatomical structures as shown by in situ hybridization and found to physically interact. Finally, we conclude that there are fundamental differences between SGZ and SVZ neurogenesis. We argue that these regulatory mechanisms are linked to the observed differential neurogenic potential of these regions. The presence of nuclear and cell surface receptors in the region specific regulatory circuits indicate the significance of niche derived extracellular factors, hormones and region specific factors such as the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis. PMID:25565969

Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

PubMed Central

McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

2013-01-01

Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

Fear extinction in the human brain: A meta-analysis of fMRI studies in healthy participants.

PubMed

Fullana, Miquel A; Albajes-Eizagirre, Anton; Soriano-Mas, Carles; Vervliet, Bram; Cardoner, Narcís; Benet, Olívia; Radua, Joaquim; Harrison, Ben J

2018-05-01

The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices. An overlapping anatomical result was obtained from the meta-analysis of extinction recall studies, except when studies directly compared an extinguished threat stimulus to an unextinguished threat stimulus (instead of a safety stimulus). In this latter instance, more consistent activation was observed in dorsolateral and ventromedial prefrontal cortex regions, together with other areas including the hippocampus. While our results partially support the notion of a shared neuroanatomy between human and rodent models of extinction processes, they also encourage an expanded account of the neural basis of human fear extinction. Copyright © 2018 Elsevier Ltd. All rights reserved.

What Can the Organization of the Brain’s Default Mode Network Tell us About Self-Knowledge?

PubMed Central

Moran, Joseph M.; Kelley, William M.; Heatherton, Todd F.

2013-01-01

Understanding ourselves has been a fundamental topic for psychologists and philosophers alike. In this paper we review the evidence linking specific brain structures to self-reflection. The brain regions most associated with self-reflection are the posterior cingulate and medial prefrontal (mPFC) cortices, together known as the cortical midline structures (CMSs). We review evidence arguing that self-reflection is special in memory, while noting that these brain regions are often engaged when we think about others in our social worlds. Based on the CMSs’ patterns of connectivity and activity, we speculate about three possible interpretations of their role in supporting self-reflection that are somewhat overlapping, and not intended to be mutually exclusive. First, self may be a powerful, but ordinary case for a cognitive system specialized for thinking about people. Second, mPFC may serve as a processing “hub,” binding together information from all sensory modalities with internally generated information. Third, mPFC may serve as a cortical director of thought, helping to guide moment-by-moment conscious processing. Suggestions are made for future research avenues aimed at testing such possibilities. PMID:23882210

Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality

PubMed Central

Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio

2017-01-01

Abstract The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project. Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders. PMID:28122961

Genomics studies on musical aptitude, music perception, and practice.

PubMed

Järvelä, Irma

2018-03-23

When searching for genetic markers inherited together with musical aptitude, genes affecting inner ear development and brain function were identified. The alpha-synuclein gene (SNCA), located in the most significant linkage region of musical aptitude, was overexpressed when listening and performing music. The GATA-binding protein 2 gene (GATA2) was located in the best associated region of musical aptitude and regulates SNCA in dopaminergic neurons, thus linking DNA- and RNA-based studies of music-related traits together. In addition to SNCA, several other genes were linked to dopamine metabolism. Mutations in SNCA predispose to Lewy-body dementia and cause Parkinson disease in humans and affect song production in songbirds. Several other birdsong genes were found in transcriptome analysis, suggesting a common evolutionary background of sound perception and production in humans and songbirds. Regions of positive selection with musical aptitude contained genes affecting auditory perception, cognitive performance, memory, human language development, and song perception and production of songbirds. The data support the role of dopaminergic pathway and their link to the reward mechanism as a molecular determinant in positive selection of music. Integration of gene-level data from the literature across multiple species prioritized activity-dependent immediate early genes as candidate genes in musical aptitude and listening to and performing music. © 2018 New York Academy of Sciences.

The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

PubMed

Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

2014-08-01

Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition

PubMed Central

Pu, Weidan; Rolls, Edmund T.; Guo, Shuixia; Liu, Haihong; Yu, Yun; Xue, Zhimin; Feng, Jianfeng; Liu, Zhening

2014-01-01

In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity. PMID:25389520

Emotion processing in joint hypermobility: A potential link to the neural bases of anxiety and related somatic symptoms in collagen anomalies.

PubMed

Mallorquí-Bagué, N; Bulbena, A; Roé-Vellvé, N; Hoekzema, E; Carmona, S; Barba-Müller, E; Fauquet, J; Pailhez, G; Vilarroya, O

2015-06-01

Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility. Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging. Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis. Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Neural Mechanisms of Episodic Retrieval Support Divergent Creative Thinking.

PubMed

Madore, Kevin P; Thakral, Preston P; Beaty, Roger E; Addis, Donna Rose; Schacter, Daniel L

2017-11-17

Prior research has indicated that brain regions and networks that support semantic memory, top-down and bottom-up attention, and cognitive control are all involved in divergent creative thinking. Kernels of evidence suggest that neural processes supporting episodic memory-the retrieval of particular elements of prior experiences-may also be involved in divergent thinking, but such processes have typically been characterized as not very relevant for, or even a hindrance to, creative output. In the present study, we combine functional magnetic resonance imaging with an experimental manipulation to test formally, for the first time, episodic memory's involvement in divergent thinking. Following a manipulation that facilitates detailed episodic retrieval, we observed greater neural activity in the hippocampus and stronger connectivity between a core brain network linked to episodic processing and a frontoparietal brain network linked to cognitive control during divergent thinking relative to an object association control task that requires little divergent thinking. Stronger coupling following the retrieval manipulation extended to a subsequent resting-state scan. Neural effects of the episodic manipulation were consistent with behavioral effects of enhanced idea production on divergent thinking but not object association. The results indicate that conceptual frameworks should accommodate the idea that episodic retrieval can function as a component process of creative idea generation, and highlight how the brain flexibly utilizes the retrieval of episodic details for tasks beyond simple remembering. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Correlation between white matter microstructure and executive functions suggests early developmental influence on long fibre tracts in preterm born adolescents.

PubMed

Vollmer, Brigitte; Lundequist, Aiko; Mårtensson, Gustaf; Nagy, Zoltan; Lagercrantz, Hugo; Smedler, Ann-Charlotte; Forssberg, Hans

2017-01-01

Executive functions are frequently a weakness in children born preterm. We examined associations of executive functions and general cognitive abilities with brain structure in preterm born adolescents who were born with appropriate weight for gestational age and who have no radiological signs of preterm brain injury on neuroimaging. The Stockholm Neonatal Project (SNP) is a longitudinal, population-based study of children born preterm (<36 weeks of gestation) with very low birth weight (<1501g) between 1988-1993. At age 18 years (mean 18 years, SD 2 weeks) 134 preterm born and 94 full term participants underwent psychological assessment (general intelligence, executive function measures). Of these, 71 preterm and 63 full term participants underwent Magnetic Resonance Imaging (MRI) at mean 15.2 years (range 12-18 years), including 3D T1-weighted images for volumetric analyses and Diffusion Tensor Imaging (DTI) for assessment of white matter microstructure. Group comparisons of regional grey and white matter volumes and fractional anisotropy (FA, as a measure of white matter microstructure) and, within each group, correlation analyses of cognitive measures with MRI metrics were carried out. Significant differences in grey and white matter regional volumes and widespread differences in FA were seen between the two groups. No significant correlations were found between cognitive measures and brain volumes in any group after correction for multiple comparisons. However, there were significant correlations between FA in projection fibres and long association fibres, linking frontal, temporal, parietal, and occipital lobes, and measures of executive function and general cognitive abilities in the preterm born adolescents, but not in the term born adolescents. In persons born preterm, in the absence of perinatal brain injury on visual inspection of MRI, widespread alterations in regional brain tissue volumes and microstructure are present in adolescence/young adulthood. Importantly, these alterations in WM tracts are correlated with measures of executive function and general cognitive abilities. Our findings suggest that disturbance of neural pathways, rather than changes in regional brain volumes, are involved in the impaired cognitive functions.

Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions.

PubMed

Correia, Joao M; Jansma, Bernadette M B; Bonte, Milene

2015-11-11

The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception. Copyright © 2015 the authors 0270-6474/15/3515015-11$15.00/0.

Brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome.

PubMed

Tajerian, Maral; Leu, David; Zou, Yani; Sahbaie, Peyman; Li, Wenwu; Khan, Hamda; Hsu, Vivian; Kingery, Wade; Huang, Ting Ting; Becerra, Lino; Clark, J David

2014-10-01

Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions. The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review.

PubMed

Li, Mingmei; Caeyenberghs, Karen

2018-05-20

In addition to the burden of a life-threatening diagnosis, cancer patients are struggling with adverse side-effects from cancer treatment. Chemotherapy has been linked to an array of cognitive impairments and alterations in brain structure and function ("chemobrain"). In this review, we summarized the existing evidence that evaluate the changes in cognitive functioning and brain with chemotherapy, as assessed using structural and functional MRI-based techniques in a longitudinal design. This review followed the latest PRISMA guidelines using Embase, Medline, PsychINFO, Scopus, and Web of Science databases with date restrictions from 2012-2017. Fourteen research articles met the key inclusion criteria: (i) the studies involved adult cancer patients (mean age≥18); (ii) the use of chemotherapy in the treatment of cancer; (iii) pre-post assessment of behavioral and brain-based outcomes; and (iv) abstracts written in English. Effect sizes of subjective and objective cognitive impairments from the reviewed studies were estimated using Cohen's d or z-scores. We calculated percentage of mean change or effect sizes for main neuroimaging findings when data were available. Strength of the correlations between brain alterations and cognitive changes was obtained using squared correlation coefficients. We showed small to medium effect sizes on individual tests of attention, processing speed, verbal memory, and executive control; and medium effect sizes on self-report questionnaires. Neuroimaging data showed reduced grey matter density in cancer patients in frontal, parietal, and temporal regions. Changes in brain function (brain activation and cerebral blood flow) were observed with cancer across functional networks involving (pre)frontal, parietal, occipital, temporal, and cerebellar regions. Data from diffusion-weighted MRI suggested reduced white matter integrity involving the superior longitudinal fasciculus, corpus callosum, forceps major, and corona radiate, and altered structural connectivity across the whole brain network. Finally, we observed moderate-to-strong correlations between worsening cognitive function and morphological changes in frontal brain regions. While MRI is a powerful tool for detection of longitudinal brain changes in the 'chemobrain', the underlying biological mechanisms are still unclear. Continued work in this field will hopefully detect MRI metrics to be used as biomarkers to help guide cognitive treatment at the individual cancer patient level. Copyright © 2018. Published by Elsevier Ltd.

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.

Altered Brain Long-Range Functional Interactions Underlying the Link Between Aberrant Self-experience and Self-other Relationship in First-Episode Schizophrenia

PubMed Central

Ebisch, Sjoerd J. H.; Mantini, Dante; Northoff, Georg; Salone, Anatolia; De Berardis, Domenico; Ferri, Francesca; Ferro, Filippo M.; Di Giannantonio, Massimo; Romani, Gian L.; Gallese, Vittorio

2014-01-01

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain. PMID:24191160

Cortical Brain Atrophy and Intra-Individual Variability in Neuropsychological Test Performance in HIV Disease

PubMed Central

HINES, Lindsay J.; MILLER, Eric N.; HINKIN, Charles H.; ALGER, Jeffery R.; BARKER, Peter; GOODKIN, Karl; MARTIN, Eileen M.; MARUCA, Victoria; RAGIN, Ann; SACKTOR, Ned; SANDERS, Joanne; SELNES, Ola; BECKER, James T.

2015-01-01

Objective To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Methods Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV−) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Results Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. Conclusions IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests. PMID:26303224

Causal Interactions between Frontalθ – Parieto-Occipitalα2 Predict Performance on a Mental Arithmetic Task

PubMed Central

Dimitriadis, Stavros I.; Sun, Yu; Thakor, Nitish V.; Bezerianos, Anastasios

2016-01-01

Many neuroimaging studies have demonstrated the different functional contributions of spatially distinct brain areas to working memory (WM) subsystems in cognitive tasks that demand both local information processing and interregional coordination. In WM cognitive task paradigms employing electroencephalography (EEG), brain rhythms such as θ and α have been linked to specific functional roles over given brain areas, but their functional coupling has not been extensively studied. Here we analyzed an arithmetic task with five cognitive workload levels (CWLs) and demonstrated functional/effective coupling between the two WM subsystems: the central executive located over frontal (F) brain areas that oscillates on the dominant θ rhythm (Frontalθ/Fθ) and the storage buffer located over parieto-occipital (PO) brain areas that operates on the α2 dominant brain rhythm (Parieto-Occipitalα2/POα2). We focused on important differences between and within WM subsystems in relation to behavioral performance. A repertoire of brain connectivity estimators was employed to elucidate the distinct roles of amplitude, phase within and between frequencies, and the hierarchical role of functionally specialized brain areas related to the task. Specifically, for each CWL, we conducted a) a conventional signal power analysis within both frequency bands at Fθ and POα2, b) the intra- and inter-frequency phase interactions between Fθ and POα2, and c) their causal phase and amplitude relationship. We found no significant statistical difference of signal power or phase interactions between correct and wrong answers. Interestingly, the study of causal interactions between Fθ and POα2 revealed frontal brain region(s) as the leader, while the strength differentiated between correct and wrong responses in every CWL with absolute accuracy. Additionally, zero time-lag between bilateral Fθ and right POa2 could serve as an indicator of mental calculation failure. Overall, our study highlights the significant role of coordinated activity between Fθ and POα2 via their causal interactions and the timing for arithmetic performance. PMID:27683547

When three is not some: on the pragmatics of numerals.

PubMed

Shetreet, Einat; Chierchia, Gennaro; Gaab, Nadine

2014-04-01

Both numerals and quantifiers (like some) have more than one possible interpretation (i.e., weak and strong interpretations). Some studies have found similar behavior for numerals and quantifiers, whereas others have shown critical differences. It is, therefore, debated whether they are processed in the same way. A previous fMRI investigation showed that the left inferior frontal gyrus is linked to the computation of the strong interpretation of quantifiers (derived by a scalar implicature) and that the left middle frontal gyrus and the medial frontal gyrus are linked to processing the mismatch between the strong interpretation of quantifiers and the context in which they are presented. In the current study, we attempted to characterize the similarities and differences between numbers and quantifiers by examining brain activation patterns related to the processing of numerals in these brain regions. When numbers were presented in a mismatch context (i.e., where their strong interpretation did not match the context), they elicited brain activations similar to those previously observed with quantifiers in the same context type. Conversely, in a match context (i.e., where both interpretations of the scalar item matched the context), numbers elicited a different activation pattern than the one observed with quantifiers: Left inferior frontal gyrus activations in response to the match condition showed decrease for numbers (but not for quantifiers). Our results support previous findings suggesting that, although they share some features, numbers and quantifiers are processed differently. We discuss our results in light of various theoretical approaches linked to the representation of numerals.

Neurotensin inversely modulates maternal aggression

PubMed Central

Gammie, Stephen C.; D’Anna, Kimberly L.; Gerstein, Hilary; Stevenson, Sharon A.

2008-01-01

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT’s role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. PMID:19118604

Neural Correlates and Connectivity underlying Stress-related Impulse Control Difficulties in Alcoholism

PubMed Central

Seo, Dongju; Lacadie, Cheryl M.; Sinha, Rajita

2016-01-01

BACKGROUND Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. METHOD The current study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients and 37 demographically-matched healthy controls were examined during brief individualized imagery trials of stress, alcohol-cue and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale (DERS). RESULTS Impulse control difficulties in AUD patients were significantly associated with hypoactive response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p<0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex (ACC) compared to controls, which are core regions of emotion regulation, suggesting AUD patients’ decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p<0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p<0.05, with adjusted Bonferroni correction). CONCLUSION Hypoactive response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. PMID:27501356

Neural Correlates and Connectivity Underlying Stress-Related Impulse Control Difficulties in Alcoholism.

PubMed

Seo, Dongju; Lacadie, Cheryl M; Sinha, Rajita

2016-09-01

Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. This study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale. Impulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p < 0.05, with adjusted Bonferroni correction). Hypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. Copyright © 2016 by the Research Society on Alcoholism.

Restoration of Normal Cerebral Oxygen Consumption with Rapamycin Treatment in a Rat Model of Autism-Tuberous Sclerosis.

PubMed

Chi, Oak Z; Wu, Chang-Chih; Liu, Xia; Rah, Kang H; Jacinto, Estela; Weiss, Harvey R

2015-09-01

Tuberous sclerosis (TSC) is associated with autism spectrum disorders and has been linked to metabolic dysfunction and unrestrained signaling of the mammalian target of rapamycin (mTOR). Inhibition of mTOR by rapamycin can mitigate some of the phenotypic abnormalities associated with TSC and autism, but whether this is due to the mTOR-related function in energy metabolism remains to be elucidated. In young Eker rats, an animal model of TSC and autism, which harbors a germ line heterozygous Tsc2 mutation, we previously reported that cerebral oxygen consumption was pronouncedly elevated. Young (4 weeks) male control Long-Evans and Eker rats were divided into control and rapamycin-treated (20 mg/kg once daily for 2 days) animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. We found significantly increased basal O2 consumption in the cortex (8.7 ± 1.5 ml O2/min/100 g Eker vs. 2.7 ± 0.2 control), hippocampus, pons and cerebellum. Regional cerebral blood flow and cerebral O2 extractions were also elevated in all brain regions. Rapamycin had no significant effect on O2 consumption in any brain region of the control rats, but significantly reduced consumption in the cortex (4.1 ± 0.3) and all other examined regions of the Eker rats. Phosphorylation of mTOR and S6K1 was similar in the two groups and equally reduced by rapamycin. Thus, a rapamycin-sensitive, mTOR-dependent but S6K1-independent, signal led to enhanced oxidative metabolism in the Eker brain. We found decreased Akt phosphorylation in Eker but not Long-Evans rat brains, suggesting that this may be related to the increased cerebral O2 consumption in the Eker rat. Our findings suggest that rapamycin targeting of Akt to restore normal cerebral metabolism could have therapeutic potential in tuberous sclerosis and autism.

Neural Correlates of Attitude Change Following Positive and Negative Advertisements

PubMed Central

Kato, Junko; Ide, Hiroko; Kabashima, Ikuo; Kadota, Hiroshi; Takano, Kouji; Kansaku, Kenji

2009-01-01

Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour. PMID:19503749

Women are better at seeing faces where there are none: an ERP study of face pareidolia

PubMed Central

Galli, Jessica

2016-01-01

Event-related potentials (ERPs) were recorded in 26 right-handed students while they detected pictures of animals intermixed with those of familiar objects, faces and faces-in-things (FITs). The face-specific N170 ERP component over the right hemisphere was larger in response to faces and FITs than to objects. The vertex positive potential (VPP) showed a difference in FIT encoding processes between males and females at frontal sites; while for men, the FIT stimuli elicited a VPP of intermediate amplitude (between that for faces and objects), for women, there was no difference in VPP responses to faces or FITs, suggesting a marked anthropomorphization of objects in women. SwLORETA source reconstructions carried out to estimate the intracortical generators of ERPs in the 150–190 ms time window showed how, in the female brain, FIT perception was associated with the activation of brain areas involved in the affective processing of faces (right STS, BA22; posterior cingulate cortex, BA22; and orbitofrontal cortex, BA10) in addition to regions linked to shape processing (left cuneus, BA18/30). Conversely, in the men, the activation of occipito/parietal regions was prevalent, with a considerably smaller activation of BA10. The data suggest that the female brain is more inclined to anthropomorphize perfectly real objects compared to the male brain. PMID:27217120

Structural brain aging and speech production: a surface-based brain morphometry study.

PubMed

Tremblay, Pascale; Deschamps, Isabelle

2016-07-01

While there has been a growing number of studies examining the neurofunctional correlates of speech production over the past decade, the neurostructural correlates of this immensely important human behaviour remain less well understood, despite the fact that previous studies have established links between brain structure and behaviour, including speech and language. In the present study, we thus examined, for the first time, the relationship between surface-based cortical thickness (CT) and three different behavioural indexes of sublexical speech production: response duration, reaction times and articulatory accuracy, in healthy young and older adults during the production of simple and complex meaningless sequences of syllables (e.g., /pa-pa-pa/ vs. /pa-ta-ka/). The results show that each behavioural speech measure was sensitive to the complexity of the sequences, as indicated by slower reaction times, longer response durations and decreased articulatory accuracy in both groups for the complex sequences. Older adults produced longer speech responses, particularly during the production of complex sequence. Unique age-independent and age-dependent relationships between brain structure and each of these behavioural measures were found in several cortical and subcortical regions known for their involvement in speech production, including the bilateral anterior insula, the left primary motor area, the rostral supramarginal gyrus, the right inferior frontal sulcus, the bilateral putamen and caudate, and in some region less typically associated with speech production, such as the posterior cingulate cortex.

Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

PubMed Central

Dennis, Nancy A.; Hayes, Scott M.; Prince, Steven E.; Madden, David J.; Huettel, Scott A.; Cabeza, Roberto

2009-01-01

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) compared to item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices including prefrontal regions were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging (PASA), previously reported in several cognitive domains and linked to functional compensation. PMID:18605869

Neural mechanisms of dissonance: an fMRI investigation of choice justification.

PubMed

Kitayama, Shinobu; Chua, Hannah Faye; Tompson, Steven; Han, Shihui

2013-04-01

Cognitive dissonance theory proposes that difficult choice produces negatively arousing cognitive conflict (called dissonance), which motivates the chooser to justify her decision by increasing her preference for the chosen option while decreasing her preference for the rejected option. At present, however, neural mechanisms of dissonance are poorly understood. To address this gap of knowledge, we scanned 24 young Americans as they made 60 choices between pairs of popular music CDs. As predicted, choices between CDs that were close (vs. distant) in attractiveness (referred to as difficult vs. easy choices) resulted in activations of the dorsal anterior cingulate cortex (dACC), a brain region associated with cognitive conflict, and the left anterior insula (left aINS), a region often linked with aversive emotional arousal. Importantly, a separate analysis showed that choice-justifying attitude change was predicted by the in-choice signal intensity of the posterior cingulate cortex (PCC), a region that is linked to self-processing. The three regions identified (dACC, left aINS, and PCC) were correlated, within-subjects, across choices. The results were interpreted to support the hypothesis that cognitive dissonance plays a key role in producing attitudes that justify the choice. Copyright © 2012 Elsevier Inc. All rights reserved.

Sequence-Level Mechanisms of Human Epigenome Evolution

PubMed Central

Prendergast, James G.D.; Chambers, Emily V.; Semple, Colin A.M.

2014-01-01

DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental duplication events in the human lineage. Chromatin and DNA methylation states were found to have been generally well conserved following a duplication event, with the evolution of the epigenome largely uncoupled from the total number of genetic changes in the surrounding DNA sequence. However, the epigenome at tissue-specific, distal regulatory regions was observed to be unusually prone to diverge following duplication, with particular sequence differences, altering known sequence motifs, found to be associated with divergence in patterns of DNA methylation and chromatin. Alu elements were found to have played a particularly prominent role in shaping human epigenome evolution, and we show that human-specific AluY insertion events are strongly linked to the evolution of the DNA methylation landscape and gene expression levels, including at key neurological genes in the human brain. Studying paralogous regions within the same sample enables the study of the links between genome and epigenome evolution while controlling for biological and technical variation. We show DNA methylation and chromatin divergence between duplicated regions are linked to the divergence of particular genetic motifs, with Alu elements having played a disproportionate role in the evolution of the epigenome in the human lineage. PMID:24966180

Sexually Dimorphic Patterns of Cell Proliferation in the Brain Are Linked to Seasonal Life-History Transitions in Red-Sided Garter Snakes.

PubMed

Lutterschmidt, Deborah I; Lucas, Ashley R; Karam, Ritta A; Nguyen, Vicky T; Rasmussen, Meghann R

2018-01-01

Seasonal rhythms in physiology and behavior are widespread across diverse taxonomic groups and may be mediated by seasonal changes in neurogenesis, including cell proliferation, migration, and differentiation. We examined if cell proliferation in the brain is associated with the seasonal life-history transition from spring breeding to migration and summer foraging in a free-ranging population of red-sided garter snakes ( Thamnophis sirtalis ) in Manitoba, Canada. We used the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label newly proliferated cells within the brain of adult snakes collected from the den during the mating season or from a road located along their migratory route. To assess rates of cell migration, we further categorized BrdU-labeled cells according to their location within the ventricular zone or parenchymal region of the nucleus sphericus (homolog of the amygdala), preoptic area/hypothalamus, septal nucleus, and cortex (homolog of the hippocampus). We found that cell proliferation and cell migration varied significantly with sex, the migratory status of snakes, and reproductive behavior in males. In most regions of interest, patterns of cell proliferation were sexually dimorphic, with males having significantly more BrdU-labeled cells than females prior to migration. However, during the initial stages of migration, females exhibited a significant increase in cell proliferation within the nucleus sphericus, hypothalamus, and septal nucleus, but not in any subregion of the cortex. In contrast, migrating males exhibited a significant increase in cell proliferation within the medial cortex but no other brain region. Because it is unlikely that the medial cortex plays a sexually dimorphic role in spatial memory during spring migration, we speculate that cell proliferation within the male medial cortex is associated with regulation of the hypothalamus-pituitary-adrenal axis. Finally, the only brain region where cell migration into the parenchymal region varied significantly with sex or migratory status was the hypothalamus. These results suggest that the migration of newly proliferated cells and/or the continued division of undifferentiated cells are activated earlier or to a greater extent in the hypothalamus. Our data suggest that sexually dimorphic changes in cell proliferation and cell migration in the adult brain may mediate sex differences in the timing of seasonal life-history transitions.

Sexually Dimorphic Patterns of Cell Proliferation in the Brain Are Linked to Seasonal Life-History Transitions in Red-Sided Garter Snakes

PubMed Central

Lutterschmidt, Deborah I.; Lucas, Ashley R.; Karam, Ritta A.; Nguyen, Vicky T.; Rasmussen, Meghann R.

2018-01-01

Seasonal rhythms in physiology and behavior are widespread across diverse taxonomic groups and may be mediated by seasonal changes in neurogenesis, including cell proliferation, migration, and differentiation. We examined if cell proliferation in the brain is associated with the seasonal life-history transition from spring breeding to migration and summer foraging in a free-ranging population of red-sided garter snakes (Thamnophis sirtalis) in Manitoba, Canada. We used the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) to label newly proliferated cells within the brain of adult snakes collected from the den during the mating season or from a road located along their migratory route. To assess rates of cell migration, we further categorized BrdU-labeled cells according to their location within the ventricular zone or parenchymal region of the nucleus sphericus (homolog of the amygdala), preoptic area/hypothalamus, septal nucleus, and cortex (homolog of the hippocampus). We found that cell proliferation and cell migration varied significantly with sex, the migratory status of snakes, and reproductive behavior in males. In most regions of interest, patterns of cell proliferation were sexually dimorphic, with males having significantly more BrdU-labeled cells than females prior to migration. However, during the initial stages of migration, females exhibited a significant increase in cell proliferation within the nucleus sphericus, hypothalamus, and septal nucleus, but not in any subregion of the cortex. In contrast, migrating males exhibited a significant increase in cell proliferation within the medial cortex but no other brain region. Because it is unlikely that the medial cortex plays a sexually dimorphic role in spatial memory during spring migration, we speculate that cell proliferation within the male medial cortex is associated with regulation of the hypothalamus-pituitary-adrenal axis. Finally, the only brain region where cell migration into the parenchymal region varied significantly with sex or migratory status was the hypothalamus. These results suggest that the migration of newly proliferated cells and/or the continued division of undifferentiated cells are activated earlier or to a greater extent in the hypothalamus. Our data suggest that sexually dimorphic changes in cell proliferation and cell migration in the adult brain may mediate sex differences in the timing of seasonal life-history transitions.

Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

PubMed

Qiu, Y-W; Su, H-H; Lv, X-F; Jiang, G-H

2015-01-01

Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the duration of codeine-containing syrup use in chronic users. Chronic codeine-containing syrup abuse may be associated with disruptions in brain WM integrity. These WM microstructural deficits may be linked to higher impulsivity in chronic codeine-containing syrup users. © 2015 by American Journal of Neuroradiology.

Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

PubMed

Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

2016-01-01

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition

PubMed Central

Schilbach, Leonhard; Bzdok, Danilo; Timmermans, Bert; Fox, Peter T.; Laird, Angela R.; Vogeley, Kai; Eickhoff, Simon B.

2012-01-01

Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. PMID:22319593

The semantic anatomical network: Evidence from healthy and brain-damaged patient populations.

PubMed

Fang, Yuxing; Han, Zaizhu; Zhong, Suyu; Gong, Gaolang; Song, Luping; Liu, Fangsong; Huang, Ruiwang; Du, Xiaoxia; Sun, Rong; Wang, Qiang; He, Yong; Bi, Yanchao

2015-09-01

Semantic processing is central to cognition and is supported by widely distributed gray matter (GM) regions and white matter (WM) tracts. The exact manner in which GM regions are anatomically connected to process semantics remains unknown. We mapped the semantic anatomical network (connectome) by conducting diffusion imaging tractography in 48 healthy participants across 90 GM "nodes," and correlating the integrity of each obtained WM edge and semantic performance across 80 brain-damaged patients. Fifty-three WM edges were obtained whose lower integrity associated with semantic deficits and together with their linked GM nodes constitute a semantic WM network. Graph analyses of this network revealed three structurally segregated modules that point to distinct semantic processing components and identified network hubs and connectors that are central in the communication across the subnetworks. Together, our results provide an anatomical framework of human semantic network, advancing the understanding of the structural substrates supporting semantic processing. © 2015 Wiley Periodicals, Inc.

Neural mechanisms of behavioral change in young adults with high-functioning autism receiving virtual reality social cognition training: A pilot study.

PubMed

Yang, Y J Daniel; Allen, Tandra; Abdullahi, Sebiha M; Pelphrey, Kevin A; Volkmar, Fred R; Chapman, Sandra B

2018-05-01

Measuring treatment efficacy in individuals with Autism Spectrum Disorder (ASD) relies primarily on behaviors, with limited evidence as to the neural mechanisms underlying these behavioral gains. This pilot study addresses this void by investigating neural and behavioral changes in a Phase I trial in young adults with high-functioning ASD who received an evidence-based behavioral intervention, Virtual Reality-Social Cognition Training over 5 weeks for a total of 10 hr. The participants were tested pre- and post-training with a validated biological/social versus scrambled/nonsocial motion neuroimaging task, previously shown to activate regions within the social brain networks. Three significant brain-behavior changes were identified. First, the right posterior superior temporal sulcus, a hub for socio-cognitive processing, showed increased brain activation to social versus nonsocial stimuli in individuals with greater gains on a theory-of-mind measure. Second, the left inferior frontal gyrus, a region for socio-emotional processing, tracked individual gains in emotion recognition with decreased activation to social versus nonsocial stimuli. Finally, the left superior parietal lobule, a region for visual attention, showed significantly decreased activation to nonsocial versus social stimuli across all participants, where heightened attention to nonsocial contingencies has been considered a disabling aspect of ASD. This study provides, albeit preliminary, some of the first evidence of the harnessable neuroplasticity in adults with ASD through an age-appropriate intervention in brain regions tightly linked to social abilities. This pilot trial motivates future efforts to develop and test social interventions to improve behaviors and supporting brain networks in adults with ASD. Autism Res 2018, 11: 713-725. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. This study addresses how the behavioral changes after treatment for ASD reflect underlying brain changes. Before and after receiving VR-SCT, young adults with high-functioning ASD passively viewed biological motion stimuli in a MRI scanner, tapping changes in the social brain network. The results reveal neuroplasticity in this age population, extending the window of opportunity for interventions to impact social competency in adults with ASD. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.

Grey matter correlates of autistic traits in women with anorexia nervosa.

PubMed

Björnsdotter, Malin; Davidovic, Monika; Karjalainen, Louise; Starck, Göran; Olausson, Håkan; Wentz, Elisabet

2018-03-01

Patients with anorexia nervosa exhibit higher levels of behaviours typically associated with autism-spectrum disorder (ASD), but the neural basis is unclear. We sought to determine whether elevated autistic traits in women with anorexia nervosa may be reflected in cortical morphology. We used voxel-based morphometry (VBM) to examine regional grey matter volumes in high-resolution MRI structural brain scans in women with anorexia nervosa and matched healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess autistic traits. Women with anorexia nervosa ( n = 25) had higher AQ scores and lower bilateral superior temporal sulcus (STS) grey matter volumes than the control group ( n = 25). The AQ scores correlated negatively with average left STS grey matter volume in women with anorexia nervosa. We did not control for cognitive ability and examined only women with ongoing anorexia nervosa. Elevated autistic traits in women with anorexia nervosa are associated with morphometric alterations of brain areas linked to social cognition. This finding provides neurobiological support for the behavioural link between anorexia nervosa and ASD and emphasizes the importance of recognizing autistic traits in preventing and treating anorexia nervosa.

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

PubMed Central

Tulino, Raffaella; Benjamin, Agnesska C.; Jolinon, Nelly; Smith, Donna L.; Chini, Eduardo N.; Carnemolla, Alisia; Bates, Gillian P.

2016-01-01

Huntington’s disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies. PMID:26815359

Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype.

PubMed

Herting, Megan M; Keenan, Madison F; Nagel, Bonnie J

2016-01-01

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual's genes may influence these relationships.

Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype

PubMed Central

Herting, Megan M.; Keenan, Madison F.; Nagel, Bonnie J.

2016-01-01

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual’s genes may influence these relationships. PMID:27445764

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease

PubMed Central

Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J.; Barrick, Thomas R.; Markus, Hugh S.

2016-01-01

Abstract Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson’s R = −0.69, P < 1 × 10 −7 ), and significant grey matter loss and whole brain atrophy occurs annually ( P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity. PMID:26936939

Impairment of visuospatial/visuoconstructional skills in multiple sclerosis patients: the correlation with regional lesion load and subcortical atrophy.

PubMed

Marasescu, R; Cerezo Garcia, M; Aladro Benito, Y

2016-04-01

About 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS-VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. To evaluate the relationship between VS-VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. Of 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS-VC impairments in the following tests: Incomplete picture, Block design (WAIS-III), and Rey-Osterrieth complex figure test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of school) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (Block design: P=.001; Rey-Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (Block design: P=.000; Rey-Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (Incomplete picture; P=.002). Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Interactive effects of genetic polymorphisms and childhood adversity on brain morphologic changes in depression.

PubMed

Kim, Yong-Ku; Ham, Byung-Joo; Han, Kyu-Man

2018-03-10

The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry. Copyright © 2018 Elsevier Inc. All rights reserved.

Obesity and Structural Brain Integrity in Older Women: The Women’s Health Initiative Magnetic Resonance Imaging Study

PubMed Central

Gaussoin, Sarah A.; Wassertheil-Smoller, Sylvia; Limacher, Marian; Casanova, Ramon; Yaffe, Kristine; Resnick, Susan M.; Espeland, Mark A.

2016-01-01

Background: Midlife obesity has been linked to age-related brain atrophy and risk of dementia, but the relationships are less clear for older individuals. These associations may be explained by changes in appetite or metabolism in the dementia prodrome; thus, prospective studies with adequate follow-up are needed. We examined the associations that obesity (body mass index, BMI) and change in BMI over an average of 6.6 (1.0–9.1) years have with global and regional brain and white matter lesion volumes in a sample of 1,366 women aged 65–80. Methods: Least square means for regional brain volumes and white matter lesion loads for women grouped by BMI and changes in BMI were generated from multivariable linear models with and without adjustment for demographic and health covariates. Results: Both global obesity and increase in BMI were associated with lower cerebrospinal fluid and higher specific brain volumes (ps < .05), after controlling for diabetes and other cerebrovascular disease risk factors. Obesity, but not change in BMI, predicted lower lesion loads for the total, parietal, and occipital white matter (ps < .05). Conclusions: Obesity in this cohort is associated with less brain atrophy and lower ischemic lesion loads. The findings are consistent with our previous report of worse cognitive performance in association with weight loss (probably not due to frailty) in this cohort and in line with the idea of the “obesity paradox” as differences in dementia risk vary across time, whereby midlife obesity seems to be a predictor of dementia, whereas weight loss seems to be a better predictor at older ages. PMID:26961581

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM.

PubMed

Bodini, Benedetta; Khaleeli, Zhaleh; Cercignani, Mara; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2009-09-01

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM. 2009 Wiley-Liss, Inc.

Resting-state fMRI and social cognition: An opportunity to connect.

PubMed

Doruyter, Alex; Groenewold, Nynke A; Dupont, Patrick; Stein, Dan J; Warwick, James M

2017-09-01

Many psychiatric disorders are characterized by altered social cognition. The importance of social cognition has previously been recognized by the National Institute of Mental Health Research Domain Criteria project, in which it features as a core domain. Social task-based functional magnetic resonance imaging (fMRI) currently offers the most direct insight into how the brain processes social information; however, resting-state fMRI may be just as important in understanding the biology and network nature of social processing. Resting-state fMRI allows researchers to investigate the functional relationships between brain regions in a neutral state: so-called resting functional connectivity (RFC). There is evidence that RFC is predictive of how the brain processes information during social tasks. This is important because it shifts the focus from possibly context-dependent aberrations to context-independent aberrations in functional network architecture. Rather than being analysed in isolation, the study of resting-state brain networks shows promise in linking results of task-based fMRI results, structural connectivity, molecular imaging findings, and performance measures of social cognition-which may prove crucial in furthering our understanding of the social brain. Copyright © 2017 John Wiley & Sons, Ltd.

Linking brain, mind and behavior.

PubMed

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

2009-08-01

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

Decreased centrality of cortical volume covariance networks in autism spectrum disorders.

PubMed

Balardin, Joana Bisol; Comfort, William Edgar; Daly, Eileen; Murphy, Clodagh; Andrews, Derek; Murphy, Declan G M; Ecker, Christine; Sato, João Ricardo

2015-10-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by atypical structural and functional brain connectivity. Complex network analysis has been mainly used to describe altered network-level organization for functional systems and white matter tracts in ASD. However, atypical functional and structural connectivity are likely to be also linked to abnormal development of the correlated structure of cortical gray matter. Such covariations of gray matter are particularly well suited to the investigation of the complex cortical pathology of ASD, which is not confined to isolated brain regions but instead acts at the systems level. In this study, we examined network centrality properties of gray matter networks in adults with ASD (n = 84) and neurotypical controls (n = 84) using graph theoretical analysis. We derived a structural covariance network for each group using interregional correlation matrices of cortical volumes extracted from a surface-based parcellation scheme containing 68 cortical regions. Differences between groups in closeness network centrality measures were evaluated using permutation testing. We identified several brain regions in the medial frontal, parietal and temporo-occipital cortices with reductions in closeness centrality in ASD compared to controls. We also found an association between an increased number of autistic traits and reduced centrality of visual nodes in neurotypicals. Our study shows that ASD are accompanied by atypical organization of structural covariance networks by means of a decreased centrality of regions relevant for social and sensorimotor processing. These findings provide further evidence for the altered network-level connectivity model of ASD. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

PubMed

Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

2017-10-21

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Somatosensory Representations Link the Perception of Emotional Expressions and Sensory Experience.

PubMed

Kragel, Philip A; LaBar, Kevin S

2016-01-01

Studies of human emotion perception have linked a distributed set of brain regions to the recognition of emotion in facial, vocal, and body expressions. In particular, lesions to somatosensory cortex in the right hemisphere have been shown to impair recognition of facial and vocal expressions of emotion. Although these findings suggest that somatosensory cortex represents body states associated with distinct emotions, such as a furrowed brow or gaping jaw, functional evidence directly linking somatosensory activity and subjective experience during emotion perception is critically lacking. Using functional magnetic resonance imaging and multivariate decoding techniques, we show that perceiving vocal and facial expressions of emotion yields hemodynamic activity in right somatosensory cortex that discriminates among emotion categories, exhibits somatotopic organization, and tracks self-reported sensory experience. The findings both support embodied accounts of emotion and provide mechanistic insight into how emotional expressions are capable of biasing subjective experience in those who perceive them.

Somatosensory Representations Link the Perception of Emotional Expressions and Sensory Experience123

PubMed Central

2016-01-01

Abstract Studies of human emotion perception have linked a distributed set of brain regions to the recognition of emotion in facial, vocal, and body expressions. In particular, lesions to somatosensory cortex in the right hemisphere have been shown to impair recognition of facial and vocal expressions of emotion. Although these findings suggest that somatosensory cortex represents body states associated with distinct emotions, such as a furrowed brow or gaping jaw, functional evidence directly linking somatosensory activity and subjective experience during emotion perception is critically lacking. Using functional magnetic resonance imaging and multivariate decoding techniques, we show that perceiving vocal and facial expressions of emotion yields hemodynamic activity in right somatosensory cortex that discriminates among emotion categories, exhibits somatotopic organization, and tracks self-reported sensory experience. The findings both support embodied accounts of emotion and provide mechanistic insight into how emotional expressions are capable of biasing subjective experience in those who perceive them. PMID:27280154

Mapping a multidimensional emotion in response to television commercials.

PubMed

Morris, Jon D; Klahr, Nelson J; Shen, Feng; Villegas, Jorge; Wright, Paul; He, Guojun; Liu, Yijun

2009-03-01

Unlike previous emotional studies using functional neuroimaging that have focused on either locating discrete emotions in the brain or linking emotional response to an external behavior, this study investigated brain regions in order to validate a three-dimensional construct--namely pleasure, arousal, and dominance (PAD) of emotion induced by marketing communication. Emotional responses to five television commercials were measured with Advertisement Self-Assessment Manikins (AdSAM) for PAD and with functional magnetic resonance imaging (fMRI) to identify corresponding patterns of brain activation. We found significant differences in the AdSAM scores on the pleasure and arousal rating scales among the stimuli. Using the AdSAM response as a model for the fMRI image analysis, we showed bilateral activations in the inferior frontal gyri and middle temporal gyri associated with the difference on the pleasure dimension, and activations in the right superior temporal gyrus and right middle frontal gyrus associated with the difference on the arousal dimension. These findings suggest a dimensional approach of constructing emotional changes in the brain and provide a better understanding of human behavior in response to advertising stimuli.

Face Patch Resting State Networks Link Face Processing to Social Cognition

PubMed Central

Schwiedrzik, Caspar M.; Zarco, Wilbert; Everling, Stefan; Freiwald, Winrich A.

2015-01-01

Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills. PMID:26348613

A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults.

PubMed

Anatürk, M; Demnitz, N; Ebmeier, K P; Sexton, C E

2018-06-22

Population aging has prompted considerable interest in identifying modifiable factors that may help protect the brain and its functions. Collectively, epidemiological studies show that leisure activities with high mental and social demands are linked with better cognition in old age. The extent to which socio-intellectual activities relate to the brain's structure is, however, not yet fully understood. This systematic review and meta-analysis summarizes magnetic resonance imaging studies that have investigated whether cognitive and social activities correlate with measures of gray and white matter volume, white matter microstructure and white matter lesions. Across eighteen included studies (total n = 8429), activity levels were associated with whole-brain white matter volume, white matter lesions and regional gray matter volume, although effect sizes were small. No associations were found for global gray matter volume and the evidence concerning white matter microstructure was inconclusive. While the causality of the reviewed associations needs to be established, our findings implicate socio-intellectual activity levels as promising targets for interventions aimed at promoting healthy brain aging. Copyright © 2018. Published by Elsevier Ltd.

Brain Modularity Mediates the Relation between Task Complexity and Performance

NASA Astrophysics Data System (ADS)

Ye, Fengdan; Yue, Qiuhai; Martin, Randi; Fischer-Baum, Simon; Ramos-Nuã+/-Ez, Aurora; Deem, Michael

Recent work in cognitive neuroscience has focused on analyzing the brain as a network, rather than a collection of independent regions. Prior studies taking this approach have found that individual differences in the degree of modularity of the brain network relate to performance on cognitive tasks. However, inconsistent results concerning the direction of this relationship have been obtained, with some tasks showing better performance as modularity increases, and other tasks showing worse performance. A recent theoretical model suggests that these inconsistencies may be explained on the grounds that high-modularity networks favor performance on simple tasks whereas low-modularity networks favor performance on complex tasks. The current study tests these predictions by relating modularity from resting-state fMRI to performance on a set of behavioral tasks. Complex and simple tasks were defined on the basis of whether they drew on executive attention. Consistent with predictions, we found a negative correlation between individuals' modularity and their performance on the complex tasks but a positive correlation with performance on the simple tasks. The results presented here provide a framework for linking measures of whole brain organization to cognitive processing.

Forever Young(er): potential age-defying effects of long-term meditation on gray matter atrophy

PubMed Central

Luders, Eileen; Cherbuin, Nicolas; Kurth, Florian

2015-01-01

While overall life expectancy has been increasing, the human brain still begins deteriorating after the first two decades of life and continues degrading further with increasing age. Thus, techniques that diminish the negative impact of aging on the brain are desirable. Existing research, although scarce, suggests meditation to be an attractive candidate in the quest for an accessible and inexpensive, efficacious remedy. Here, we examined the link between age and cerebral gray matter re-analyzing a large sample (n = 100) of long-term meditators and control subjects aged between 24 and 77 years. When correlating global and local gray matter with age, we detected negative correlations within both controls and meditators, suggesting a decline over time. However, the slopes of the regression lines were steeper and the correlation coefficients were stronger in controls than in meditators. Moreover, the age-affected brain regions were much more extended in controls than in meditators, with significant group-by-age interactions in numerous clusters throughout the brain. Altogether, these findings seem to suggest less age-related gray matter atrophy in long-term meditation practitioners. PMID:25653628

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

Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics.

PubMed

Atasoy, Selen; Deco, Gustavo; Kringelbach, Morten L; Pearson, Joel

2018-06-01

A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at "rest." Here, we introduce the concept of harmonic brain modes-fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

Connectomics-based analysis of information flow in the Drosophila brain.

PubMed

Shih, Chi-Tin; Sporns, Olaf; Yuan, Shou-Li; Su, Ta-Shun; Lin, Yen-Jen; Chuang, Chao-Chun; Wang, Ting-Yuan; Lo, Chung-Chuang; Greenspan, Ralph J; Chiang, Ann-Shyn

2015-05-18

Understanding the overall patterns of information flow within the brain has become a major goal of neuroscience. In the current study, we produced a first draft of the Drosophila connectome at the mesoscopic scale, reconstructed from 12,995 images of neuron projections collected in FlyCircuit (version 1.1). Neuron polarities were predicted according to morphological criteria, with nodes of the network corresponding to brain regions designated as local processing units (LPUs). The weight of each directed edge linking a pair of LPUs was determined by the number of neuron terminals that connected one LPU to the other. The resulting network showed hierarchical structure and small-world characteristics and consisted of five functional modules that corresponded to sensory modalities (olfactory, mechanoauditory, and two visual) and the pre-motor center. Rich-club organization was present in this network and involved LPUs in all sensory centers, and rich-club members formed a putative motor center of the brain. Major intra- and inter-modular loops were also identified that could play important roles for recurrent and reverberant information flow. The present analysis revealed whole-brain patterns of network structure and information flow. Additionally, we propose that the overall organizational scheme showed fundamental similarities to the network structure of the mammalian brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolomics studies in brain tissue: A review.

PubMed

Gonzalez-Riano, Carolina; Garcia, Antonia; Barbas, Coral

2016-10-25

Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Complementarity of Sex Differences in Brain and Behavior: From Laterality to Multi-Modal Neuroimaging

PubMed Central

Gur, Ruben C.; Gur, Raquel E.

2016-01-01

While overwhelmingly behavior is similar in males and females, and correspondingly the brains are similar, sex differences permeate both brain and behavioral measures and these differences have been the focus of increasing scrutiny by neuroscientists. Here we describe milestones of over three decades of research in brain and behavior. This research was necessarily bound by available methodology, and we began by indirect behavioral indicators of brain function such as handedness. We proceeded to using neuropsychological batteries and then to structural and functional neuroimaging that provided the foundations of a cognitive neuroscience based computerized neurocognitive battery. Sex differences were apparent and consistent in neurocognitive measures, with females performing better on memory and social cognition tasks and males on spatial processing and motor speed. Sex differences were also prominent on all major brain parameters, including higher rates of cerebral blood flow, higher percent of gray matter tissue and higher inter-hemispheric connectivity in females compared to higher percent of white matter and greater intra-hemispheric connectivity, as well as higher glucose metabolism in limbic regions in males. Many of these differences are present in childhood but they become more prominent with adolescence, perhaps linked to puberty. Together they indicate complementarity between the sexes that would result in higher adaptive diversity. PMID:27870413

Dynamic hub load predicts cognitive decline after resective neurosurgery.

PubMed

Carbo, Ellen W S; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C; Baayen, Johannes C; Klein, Martin; Geurts, Jeroen J G; Reijneveld, Jaap C; Stam, Cornelis J; Douw, Linda

2017-02-07

Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.

Influence of the topography of brain damage on depression and fatigue in patients with multiple sclerosis.

PubMed

Gobbi, C; Rocca, M A; Riccitelli, G; Pagani, E; Messina, R; Preziosa, P; Colombo, B; Rodegher, M; Falini, A; Comi, G; Filippi, M

2014-02-01

Involvement of selected central nervous system (CNS) regions has been associated with depression and fatigue in MS. We assessed whether specific regional patterns of lesion distribution and atrophy of the gray (GM) and white matter (WM) are associated with these symptoms in MS. Brain dual-echo and 3D T1-weighted images were acquired from 123 MS patients (69 depressed (D), 54 non-depressed (nD), 64 fatigued, 59 non-fatigued) and 90 controls. Lesion distribution, GM and WM atrophy were estimated using VBM and SPM8. Gender, age, disease duration and conventional MRI characteristics did not differ between D-MS and nD-MS patients. Fatigued patients experienced higher EDSS and depression than non-fatigued ones. Lesion distribution and WM atrophy were not related to depression and fatigue. Atrophy of regions in the frontal, parietal and occipital lobes had a combined effect on depression and fatigue. Atrophy of the left middle frontal gyrus and right inferior frontal gyrus were selectively related to depression. No specific pattern of GM atrophy was found to be related to fatigue. Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Beta Oscillatory Dynamics in the Prefrontal and Superior Temporal Cortices Predict Spatial Working Memory Performance.

PubMed

Proskovec, Amy L; Wiesman, Alex I; Heinrichs-Graham, Elizabeth; Wilson, Tony W

2018-05-31

The oscillatory dynamics serving spatial working memory (SWM), and how such dynamics relate to performance, are poorly understood. To address these topics, the present study recruited 22 healthy adults to perform a SWM task during magnetoencephalography (MEG). The resulting MEG data were transformed into the time-frequency domain, and significant oscillatory responses were imaged using a beamformer. Voxel time series data were extracted from the cluster peaks to quantify the dynamics, while whole-brain partial correlation maps were computed to identify regions where oscillatory strength varied with accuracy on the SWM task. The results indicated transient theta oscillations in spatially distinct subregions of the prefrontal cortices at the onset of encoding and maintenance, which may underlie selection of goal-relevant information. Additionally, strong and persistent decreases in alpha and beta oscillations were observed throughout encoding and maintenance in parietal, temporal, and occipital regions, which could serve sustained attention and maintenance processes during SWM performance. The neuro-behavioral correlations revealed that beta activity within left dorsolateral prefrontal control regions and bilateral superior temporal integration regions was negatively correlated with SWM accuracy. Notably, this is the first study to employ a whole-brain approach to significantly link neural oscillations to behavioral performance in the context of SWM.

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.

PubMed

Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

2006-10-17

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.

Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep.

PubMed

Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E

2014-01-01

The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy. © 2013.

Neural bases of eye and gaze processing: The core of social cognition

PubMed Central

Itier, Roxane J.; Batty, Magali

2014-01-01

Eyes and gaze are very important stimuli for human social interactions. Recent studies suggest that impairments in recognizing face identity, facial emotions or in inferring attention and intentions of others could be linked to difficulties in extracting the relevant information from the eye region including gaze direction. In this review, we address the central role of eyes and gaze in social cognition. We start with behavioral data demonstrating the importance of the eye region and the impact of gaze on the most significant aspects of face processing. We review neuropsychological cases and data from various imaging techniques such as fMRI/PET and ERP/MEG, in an attempt to best describe the spatio-temporal networks underlying these processes. The existence of a neuronal eye detector mechanism is discussed as well as the links between eye gaze and social cognition impairments in autism. We suggest impairments in processing eyes and gaze may represent a core deficiency in several other brain pathologies and may be central to abnormal social cognition. PMID:19428496

Neural activity in the posterior superior temporal region during eye contact perception correlates with autistic traits.

PubMed

Hasegawa, Naoya; Kitamura, Hideaki; Murakami, Hiroatsu; Kameyama, Shigeki; Sasagawa, Mutsuo; Egawa, Jun; Endo, Taro; Someya, Toshiyuki

2013-08-09

The present study investigated the relationship between neural activity associated with gaze processing and autistic traits in typically developed subjects using magnetoencephalography. Autistic traits in 24 typically developed college students with normal intelligence were assessed using the Autism Spectrum Quotient (AQ). The Minimum Current Estimates method was applied to estimate the cortical sources of magnetic responses to gaze stimuli. These stimuli consisted of apparent motion of the eyes, displaying direct or averted gaze motion. Results revealed gaze-related brain activations in the 150-250 ms time window in the right posterior superior temporal sulcus (pSTS), and in the 150-450 ms time window in medial prefrontal regions. In addition, the mean amplitude in the 150-250 ms time window in the right pSTS region was modulated by gaze direction, and its activity in response to direct gaze stimuli correlated with AQ score. pSTS activation in response to direct gaze is thought to be related to higher-order social processes. Thus, these results suggest that brain activity linking eye contact and social signals is associated with autistic traits in a typical population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers.

PubMed

London, Edythe D; Berman, Steven M; Voytek, Bradley; Simon, Sara L; Mandelkern, Mark A; Monterosso, John; Thompson, Paul M; Brody, Arthur L; Geaga, Jennifer A; Hong, Michael S; Hayashi, Kiralee M; Rawson, Richard A; Ling, Walter

2005-11-15

Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

A dual-systems perspective on addiction: contributions from neuroimaging and cognitive training.

PubMed

McClure, Samuel M; Bickel, Warren K

2014-10-01

Dual-systems theories explain lapses in self-control in terms of a conflict between automatic and deliberative modes of behavioral control. Numerous studies have now tested whether the brain areas that control behavior are organized in a manner consistent with dual-systems models. Brain regions directly associated with the mesolimbic dopamine system, the nucleus accumbens and ventromedial prefrontal cortex in particular, capture some of the features assumed by automatic processing. Regions in the lateral prefrontal cortex are more closely linked to deliberative processing and the exertion of self-control in the suppression of impulses. While identifying these regions crudely supports dual-systems theories, important modifications to what constitutes automatic and deliberative behavioral control are also suggested. Experiments have identified various means by which automatic processes may be sculpted. Additional work decomposes deliberative processes into component functions such as generalized working memory, reappraisal of emotional stimuli, and prospection. The importance of deconstructing dual-systems models into specific cognitive processes is clear for understanding and treating addiction. We discuss intervention possibilities suggested by recent research, and focus in particular on cognitive training approaches to bolster deliberative control processes that may aid quit attempts. © 2014 New York Academy of Sciences.

A dual-systems perspective on addiction: contributions from neuroimaging and cognitive training

PubMed Central

McClure, Samuel M.; Bickel, Warren K.

2014-01-01

Dual-systems theories explain lapses in self-control in terms of a conflict between automatic and deliberative modes of behavioral control. Numerous studies have now tested whether the brain areas that control behavior are organized in a manner consistent with dual-systems models. Brain regions directly associated with the mesolimbic dopamine system, the nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) in particular, capture some of the features assumed by automatic processing. Regions in the lateral prefrontal cortex (lPFC) are more closely linked to deliberative processing and the exertion of self-control in the suppression of impulses. While identifying these regions crudely supports dual-system theories, important modifications to what constitutes automatic and deliberative behavioral control are also suggested. Experiments have identified various means by which automatic processes may be sculpted. Additional work decomposes deliberative processes into component functions such as generalized working memory, reappraisal of emotional stimuli, and prospection. The importance of deconstructing dual-systems models into specific cognitive processes is clear for understanding and treating addiction. We discuss intervention possibilities suggested by recent research, and focus in particular on cognitive training approaches to bolster deliberative control processes that may aid quit attempts. PMID:25336389

Biomechanically based simulation of brain deformations for intraoperative image correction: coupling of elastic and fluid models

NASA Astrophysics Data System (ADS)

Hagemann, Alexander; Rohr, Karl; Stiehl, H. Siegfried

2000-06-01

In order to improve the accuracy of image-guided neurosurgery, different biomechanical models have been developed to correct preoperative images w.r.t. intraoperative changes like brain shift or tumor resection. All existing biomechanical models simulate different anatomical structures by using either appropriate boundary conditions or by spatially varying material parameter values, while assuming the same physical model for all anatomical structures. In general, this leads to physically implausible results, especially in the case of adjacent elastic and fluid structures. Therefore, we propose a new approach which allows to couple different physical models. In our case, we simulate rigid, elastic, and fluid regions by using the appropriate physical description for each material, namely either the Navier equation or the Stokes equation. To solve the resulting differential equations, we derive a linear matrix system for each region by applying the finite element method (FEM). Thereafter, the linear matrix systems are linked together, ending up with one overall linear matrix system. Our approach has been tested using synthetic as well as tomographic images. It turns out from experiments, that the integrated treatment of rigid, elastic, and fluid regions significantly improves the prediction results in comparison to a pure linear elastic model.

Multiple Brain Markers are Linked to Age-Related Variation in Cognition

PubMed Central

Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

2016-01-01

Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

The association between the brain and mind pops: a voxel-based morphometry study in 256 Chinese college students.

PubMed

Zhang, Lei; Li, Wenfu; Wei, Dongtao; Yang, Wenjing; Yang, Ning; Qiao, Lei; Qiu, Jiang; Zuo, Xi-Nian; Zhang, Qinglin

2016-06-01

Mind pops or involuntary semantic memories refer to words, phrases, images, or melodies that suddenly pop into one's mind without any deliberate attempt to recall them. Despite their prevalence in everyday life, research on mind pops has started only recently. Notably, mind pops are very similar to clinical involuntary phenomena such as hallucinations in schizophrenia, suggesting their potential role in pathology. The present study aimed to investigate the relationship between mind pops and the brain morphometry measured in 302 healthy young adults; after exclusions, 256 participants were included in our analyses. Specifically, the Mind Popping Questionnaire (MPQ) was employed to measure the degree of individual mind pops, whereas the Voxel-Based Morphometry (VBM) was used to compute the volumes of both gray and white matter tissues. Multiple regression analyses on MPQ and VBM metrics indicated that high-frequency mind pops were significantly associated with smaller gray matter volume in the left middle temporal gyrus as well as with larger gray and white matter volume in the right medial prefrontal cortex. This increase in mind pops is also linked to higher creativity and the personality trait of 'openness'. These data not only suggest a key role of the two regions in generating self-related thoughts, but also open a possible link between brain and creativity or personality.

The pleiotropic transcriptional regulator COUP-TFI plays multiple roles in neural development and disease.

PubMed

Bertacchi, Michele; Parisot, Josephine; Studer, Michèle

2018-04-27

Transcription factors are expressed in a dynamic fashion both in time and space during brain development, and exert their roles by activating a cascade of multiple target genes. This implies that understanding the precise function of a transcription factor becomes a challenging task. In this review, we will focus on COUP-TFI (or NR2F1), a nuclear receptor belonging to the superfamily of the steroid/thyroid hormone receptors, and considered to be one of the major transcriptional regulators orchestrating cortical arealization, cell-type specification and maturation. Recent data have unraveled the multi-faceted functions of COUP-TFI in the development of several mouse brain structures, including the neocortex, hippocampus and ganglionic eminences. Despite NR2F1 mutations and deletions in humans have been linked to a complex neurodevelopmental disease mainly associated to optic atrophy and intellectual disability, its role during the formation of the retina and optic nerve remains unclear. In light of its major influence in cortical development, we predict that its haploinsufficiency might be the cause of other cognitive diseases, not identified so far. Mouse models offer a unique opportunity of dissecting COUP-TFI function in different regions during brain assembly; hence, the importance of comparing and discussing common points linking mouse models to human patients' symptoms. Copyright © 2018 Elsevier B.V. All rights reserved.

Gray matter volume covariance patterns associated with gait speed in older adults: a multi-cohort MRI study.

PubMed

Blumen, Helena M; Brown, Lucy L; Habeck, Christian; Allali, Gilles; Ayers, Emmeline; Beauchet, Olivier; Callisaya, Michele; Lipton, Richard B; Mathuranath, P S; Phan, Thanh G; Pradeep Kumar, V G; Srikanth, Velandai; Verghese, Joe

2018-04-09

Accelerated gait decline in aging is associated with many adverse outcomes, including an increased risk for falls, cognitive decline, and dementia. Yet, the brain structures associated with gait speed, and how they relate to specific cognitive domains, are not well-understood. We examined structural brain correlates of gait speed, and how they relate to processing speed, executive function, and episodic memory in three non-demented and community-dwelling older adult cohorts (Overall N = 352), using voxel-based morphometry and multivariate covariance-based statistics. In all three cohorts, we identified gray matter volume covariance patterns associated with gait speed that included brain stem, precuneus, fusiform, motor, supplementary motor, and prefrontal (particularly ventrolateral prefrontal) cortex regions. Greater expression of these gray matter volume covariance patterns linked to gait speed were associated with better processing speed in all three cohorts, and with better executive function in one cohort. These gray matter covariance patterns linked to gait speed were not associated with episodic memory in any of the cohorts. These findings suggest that gait speed, processing speed (and to some extent executive functions) rely on shared neural systems that are subject to age-related and dementia-related change. The implications of these findings are discussed within the context of the development of interventions to compensate for age-related gait and cognitive decline.

Functional brain imaging predicts public health campaign success.

PubMed

Falk, Emily B; O'Donnell, Matthew Brook; Tompson, Steven; Gonzalez, Richard; Dal Cin, Sonya; Strecher, Victor; Cummings, Kenneth Michael; An, Lawrence

2016-02-01

Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a 'self-localizer' defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400,000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R(2) up to 0.65) and (ii) this relationship depends on message content-self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Characterization of GPR101 transcript structure and expression patterns

PubMed Central

Trivellin, Giampaolo; Bjelobaba, Ivana; Daly, Adrian F.; Larco, Darwin O.; Palmeira, Leonor; Faucz, Fabio R.; Thiry, Albert; Leal, Letícia F.; Rostomyan, Liliya; Quezado, Martha; Schernthaner-Reiter, Marie Helene; Janjic, Marija M.; Villa, Chiara; Wu, T. John; Stojilkovic, Stanko S.; Beckers, Albert; Feldman, Benjamin; Stratakis, Constantine A.

2016-01-01

We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X-LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes. GPR101 was the only gene highly expressed in their pituitary lesions, but little is known about its expression patterns. GPR101 transcripts were characterized in human tissues by 5’-RACE and RNAseq, while the putative promoter was bioinformatically predicted. We investigated GPR101 mRNA and protein expression by RT-qPCR, whole-mount in situ hybridization, and immunostaining, in human, rhesus monkey, rat, and zebrafish. We identified four GPR101 isoforms characterized by different 5’ untranslated regions (UTRs) and a common 6.1 kb-long 3’UTR. GPR101 expression was very low or absent in almost all adult human tissues examined, except for specific brain regions. Strong GPR101 staining was observed in human fetal pituitary and during adolescence, whereas very weak/absent expression was detected during childhood and adult life. In contrast to humans, adult pituitaries of monkey and rat expressed GPR101, but in different cell types. Gpr101 is expressed in the brain and pituitary during rat and zebrafish development; in rat pituitary Gpr101 is expressed only after birth and showed sexual dimorphism. This study shows that different GPR101 transcripts exist and that the brain is the major site of GPR101 expression across different species, although divergent species- and temporal-specific expression patterns are evident. These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species. PMID:27282544

Neuronal Assemblies Evidence Distributed Interactions within a Tactile Discrimination Task in Rats

PubMed Central

Deolindo, Camila S.; Kunicki, Ana C. B.; da Silva, Maria I.; Lima Brasil, Fabrício; Moioli, Renan C.

2018-01-01

Accumulating evidence suggests that neural interactions are distributed and relate to animal behavior, but many open questions remain. The neural assembly hypothesis, formulated by Hebb, states that synchronously active single neurons may transiently organize into functional neural circuits—neuronal assemblies (NAs)—and that would constitute the fundamental unit of information processing in the brain. However, the formation, vanishing, and temporal evolution of NAs are not fully understood. In particular, characterizing NAs in multiple brain regions over the course of behavioral tasks is relevant to assess the highly distributed nature of brain processing. In the context of NA characterization, active tactile discrimination tasks with rats are elucidative because they engage several cortical areas in the processing of information that are otherwise masked in passive or anesthetized scenarios. In this work, we investigate the dynamic formation of NAs within and among four different cortical regions in long-range fronto-parieto-occipital networks (primary somatosensory, primary visual, prefrontal, and posterior parietal cortices), simultaneously recorded from seven rats engaged in an active tactile discrimination task. Our results first confirm that task-related neuronal firing rate dynamics in all four regions is significantly modulated. Notably, a support vector machine decoder reveals that neural populations contain more information about the tactile stimulus than the majority of single neurons alone. Then, over the course of the task, we identify the emergence and vanishing of NAs whose participating neurons are shown to contain more information about animal behavior than randomly chosen neurons. Taken together, our results further support the role of multiple and distributed neurons as the functional unit of information processing in the brain (NA hypothesis) and their link to active animal behavior. PMID:29375324

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

PubMed

Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

2015-11-01

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of morphine on brain plasticity.

PubMed

Beltrán-Campos, V; Silva-Vera, M; García-Campos, M L; Díaz-Cintra, S

2015-04-01

Morphine shares with other opiates and drugs of abuse the ability to modify the plasticity of brain areas that regulate the morphology of dendrites and spines, which are the primary sites of excitatory synapses in regions of the brain involved in incentive motivation, rewards, and learning. In this review we discuss the impact of morphine use during the prenatal period of brain development and its long-term consequences in murines, and then link those consequences to similar effects occurring in human neonates and adults. Repeated exposure to morphine as treatment for pain in terminally ill patients produces long-term changes in the density of postsynaptic sites (dendrites and spines) in sensitive areas of the brain, such as the prefrontal cortex, the limbic system (hippocampus, amygdala), and caudate nuclei and nucleus accumbens. This article reviews the cellular mechanisms and receptors involved, primarily dopaminergic and glutamatergic receptors, as well as synaptic plasticity brought about by changes in dendritic spines in these areas. The actions of morphine on both developing and adult brains produce alterations in the plasticity of excitatory postsynaptic sites of the brain areas involved in limbic system functions (reward and learning). Doctors need further studies on plasticity in dendrites and spines and on signaling molecules, such as calcium, in order to improve treatments for addiction. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Ventral anterior cingulate cortex and social decision-making.

PubMed

Lockwood, Patricia L; Wittmann, Marco K

2018-06-07

Studies in the field of social neuroscience have recently made use of computational models of decision-making to provide new insights into how we learn about the self and others during social interactions. Importantly, these studies have increasingly drawn attention to brain areas outside of classical cortical "social brain" regions that may be critical for social processing. In particular, two portions of the ventral anterior cingulate cortex (vACC), subgenual anterior cingulate cortex and perigenual anterior cingulate cortex, have been linked to social and self learning signals, respectively. Here we discuss the emerging parallels between these studies. Uncovering the function of vACC during social interactions could provide important new avenues to understand social decision-making in health and disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

PubMed

Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

2018-05-01

Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

PubMed

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

2016-09-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

VBM-DTI correlates of verbal intelligence: a potential link to Broca's area.

PubMed

Konrad, Andreas; Vucurevic, Goran; Musso, Francesco; Winterer, Georg

2012-04-01

Human brain lesion studies first investigated the biological roots of cognitive functions including language in the late 1800s. Neuroimaging studies have reported correlation findings with general intelligence predominantly in fronto-parietal cortical areas. However, there is still little evidence about the relationship between verbal intelligence and structural properties of the brain. We predicted that verbal performance is related to language regions of Broca's and Wernicke's areas. Verbal intelligence quotient (vIQ) was assessed in 30 healthy young subjects. T1-weighted MRI and diffusion tensor imaging data sets were acquired. Voxel-wise regression analyses were used to correlate fractional anisotropy (FA) and mean diffusivity values with vIQ. Moreover, regression analyses of regional brain volume with vIQ were performed adopting voxel-based morphometry (VBM) and ROI methodology. Our analyses revealed a significant negative correlation between vIQ and FA and a significant positive correlation between vIQ and mean diffusivity in the left-hemispheric Broca's area. VBM regression analyses did not show significant results, whereas a subsequent ROI analysis of Broca's area FA peak cluster demonstrated a positive correlation of gray matter volume and vIQ. These findings suggest that cortical thickness in Broca's area contributes to verbal intelligence. Diffusion parameters predicted gray matter ratio in Broca's area more sensitive than VBM methodology.

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

PubMed Central

Whalley, H C; Papmeyer, M; Sprooten, E; Romaniuk, L; Blackwood, D H; Glahn, D C; Hall, J; Lawrie, S M; Sussmann, Je; McIntosh, A M

2012-01-01

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD. PMID:22760554

Modulation of working memory load distinguishes individuals with and without balance impairments following mild traumatic brain injury.

PubMed

Woytowicz, Elizabeth J; Sours, Chandler; Gullapalli, Rao P; Rosenberg, Joseph; Westlake, Kelly P

2018-01-01

Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2-8 weeks following mild TBI. Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years). We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network. Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population.

Structural and functional bases of inhibited temperament.

PubMed

Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M; Avery, Suzanne N; Cao, Aize; Cowan, Ronald L; Benningfield, Margaret M; Blackford, Jennifer Urbano

2014-12-01

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Huls, M. H.; Sams, C. F.

1991-01-01

Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease.

PubMed

Blanch, Marta; Mosquera, Jose Luis; Ansoleaga, Belén; Ferrer, Isidre; Barrachina, Marta

2016-02-01

Mitochondrial dysfunction is linked with the etiopathogenesis of Alzheimer disease and Parkinson disease. Mitochondria are intracellular organelles essential for cell viability and are characterized by the presence of the mitochondrial (mt)DNA. DNA methylation is a well-known epigenetic mechanism that regulates nuclear gene transcription. However, mtDNA methylation is not the subject of the same research attention. The present study shows the presence of mitochondrial 5-methylcytosine in CpG and non-CpG sites in the entorhinal cortex and substantia nigra of control human postmortem brains, using the 454 GS FLX Titanium pyrosequencer. Moreover, increased mitochondrial 5-methylcytosine levels are found in the D-loop region of mtDNA in the entorhinal cortex in brain samples with Alzheimer disease-related pathology (stages I to II and stages III to IV of Braak and Braak; n = 8) with respect to control cases. Interestingly, this region shows a dynamic pattern in the content of mitochondrial 5-methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology progression (3, 6, and 12 months of age). Finally, a loss of mitochondrial 5-methylcytosine levels in the D-loop region is found in the substantia nigra in Parkinson disease (n = 10) with respect to control cases. In summary, the present findings suggest mtDNA epigenetic modulation in human brain is vulnerable to neurodegenerative disease states. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats.

PubMed

Nakamura, K; Shirane, M; Koshikawa, N

2001-04-06

The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.

Imbalance in subregional connectivity of the right temporoparietal junction in major depression.

PubMed

Poeppl, Timm B; Müller, Veronika I; Hoffstaedter, Felix; Bzdok, Danilo; Laird, Angela R; Fox, Peter T; Langguth, Berthold; Rupprecht, Rainer; Sorg, Christian; Riedl, Valentin; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

2016-08-01

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Real-time strategy video game experience and structural connectivity - A diffusion tensor imaging study.

PubMed

Kowalczyk, Natalia; Shi, Feng; Magnuski, Mikolaj; Skorko, Maciek; Dobrowolski, Pawel; Kossowski, Bartosz; Marchewka, Artur; Bielecki, Maksymilian; Kossut, Malgorzata; Brzezicka, Aneta

2018-06-20

Experienced video game players exhibit superior performance in visuospatial cognition when compared to non-players. However, very little is known about the relation between video game experience and structural brain plasticity. To address this issue, a direct comparison of the white matter brain structure in RTS (real time strategy) video game players (VGPs) and non-players (NVGPs) was performed. We hypothesized that RTS experience can enhance connectivity within and between occipital and parietal regions, as these regions are likely to be involved in the spatial and visual abilities that are trained while playing RTS games. The possible influence of long-term RTS game play experience on brain structural connections was investigated using diffusion tensor imaging (DTI) and a region of interest (ROI) approach in order to describe the experience-related plasticity of white matter. Our results revealed significantly more total white matter connections between occipital and parietal areas and within occipital areas in RTS players compared to NVGPs. Additionally, the RTS group had an altered topological organization of their structural network, expressed in local efficiency within the occipito-parietal subnetwork. Furthermore, the positive association between network metrics and time spent playing RTS games suggests a close relationship between extensive, long-term RTS game play and neuroplastic changes. These results indicate that long-term and extensive RTS game experience induces alterations along axons that link structures of the occipito-parietal loop involved in spatial and visual processing. © 2018 Wiley Periodicals, Inc.

Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention.

PubMed

Kucyi, Aaron; Hove, Michael J; Esterman, Michael; Hutchison, R Matthew; Valera, Eve M

2017-03-01

Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out-of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Individual differences in verbal creative thinking are reflected in the precuneus.

PubMed

Chen, Qun-Lin; Xu, Ting; Yang, Wen-Jing; Li, Ya-Dan; Sun, Jiang-Zhou; Wang, Kang-Cheng; Beaty, Roger E; Zhang, Qing-Lin; Zuo, Xi-Nian; Qiu, Jiang

2015-08-01

There have been many structural and functional imaging studies of creative thinking, but combining structural and functional magnetic resonance imaging (MRI) investigations with respect to creative thinking is still lacking. Thus, the aim of the present study was to explore the associations among inter-individual verbal creative thinking and both regional homogeneity and cortical morphology of the brain surface. We related the local functional homogeneity of spontaneous brain activity to verbal creative thinking and its dimensions--fluency, originality, and flexibility--by examining these inter-individual differences in a large sample of 268 healthy college students. Results revealed that people with high verbal creative ability and high scores for the three dimensions of creativity exhibited lower regional functional homogeneity in the right precuneus. Both cortical volume and thickness of the right precuneus were positively associated with individual verbal creativity and its dimensions. Moreover, originality was negatively correlated with functional homogeneity in the left superior frontal gyrus and positively correlated with functional homogeneity in the right occipito-temporal gyrus. In contrast, flexibility was positively correlated with functional homogeneity in the left superior and middle occipital gyrus. These findings provide additional evidence of a link between verbal creative thinking and brain structure in the right precuneus--a region involved in internally--focused attention and effective semantic retrieval-and further suggest that local functional homogeneity of verbal creative thinking has neurobiological relevance that is likely based on anatomical substrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention.

PubMed

Fukudo, S; Kanazawa, M; Mizuno, T; Hamaguchi, T; Kano, M; Watanabe, S; Sagami, Y; Shoji, T; Endo, Y; Hongo, M; Itoyama, Y; Yanai, K; Tashiro, M; Aoki, M

2009-09-01

Determining the gene that plays a key role in brain-gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans. We enrolled 28 subjects without any organic disease. The study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n=14) and individuals with the l allele (genotypes l/s, l/l, l/extra-l, n=14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) stimulation on a random order. Radioactive H2[(15-)O] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping. Individuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the l allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p<0.0001). The increase in rCBF by colorectal distention of 20 mm Hg compared with 0 mm Hg was significantly larger in the left orbitofrontal cortex of individuals with the s/s genotype than that of individuals with the l allele (p<0.0001). These data suggest that individuals with a weak function of serotonin transporter respond to gut signals more in emotion-regulating brain regions. Functional gene polymorphism may partially predict the individual effect of a selective serotonin reuptake inhibitor on visceral pain.

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

PubMed

Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

2017-02-01

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.

PubMed

Suarez, Andrea N; Hsu, Ted M; Liu, Clarissa M; Noble, Emily E; Cortella, Alyssa M; Nakamoto, Emily M; Hahn, Joel D; de Lartigue, Guillaume; Kanoski, Scott E

2018-06-05

The vagus nerve is the primary means of neural communication between the gastrointestinal (GI) tract and the brain. Vagally mediated GI signals activate the hippocampus (HPC), a brain region classically linked with memory function. However, the endogenous relevance of GI-derived vagal HPC communication is unknown. Here we utilize a saporin (SAP)-based lesioning procedure to reveal that selective GI vagal sensory/afferent ablation in rats impairs HPC-dependent episodic and spatial memory, effects associated with reduced HPC neurotrophic and neurogenesis markers. To determine the neural pathways connecting the gut to the HPC, we utilize monosynaptic and multisynaptic virus-based tracing methods to identify the medial septum as a relay connecting the medial nucleus tractus solitarius (where GI vagal afferents synapse) to dorsal HPC glutamatergic neurons. We conclude that endogenous GI-derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem-septal pathway, thereby identifying a previously unknown role for the gut-brain axis in memory control.

Early gray-matter and white-matter concentration in infancy predict later language skills: a whole brain voxel-based morphometry study.

PubMed

Deniz Can, Dilara; Richards, Todd; Kuhl, Patricia K

2013-01-01

Magnetic resonance imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural response to prosocial scenes relates to subsequent giving behavior in adolescents: A pilot study.

PubMed

Tashjian, Sarah M; Weissman, David G; Guyer, Amanda E; Galván, Adriana

2018-04-01

Adolescence is characterized by extensive neural development and sensitivity to social context, both of which contribute to engaging in prosocial behaviors. Although it is established that prosocial behaviors are linked to positive outcomes in adulthood, little is known about the neural correlates of adolescents' prosociality. Identifying whether the brain is differentially responsive to varying types of social input may be important for fostering prosocial behavior. We report pilot results using new stimuli and an ecologically valid donation paradigm indicating (1) brain regions typically recruited during socioemotional processing evinced differential activation when adolescents evaluated prosocial compared with social or noninteractive scenes (N = 20, ages 13-17 years, M Age = 15.30 years), and (2) individual differences in temporoparietal junction recruitment when viewing others' prosocial behaviors were related to adolescents' own charitable giving. These novel findings have significant implications for understanding how the adolescent brain processes prosocial acts and for informing ways to support adolescents to engage in prosocial behaviors in their daily lives.

Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs

PubMed Central

Wu, Ming; Nern, Aljoscha; Williamson, W Ryan; Morimoto, Mai M; Reiser, Michael B; Card, Gwyneth M; Rubin, Gerald M

2016-01-01

Visual projection neurons (VPNs) provide an anatomical connection between early visual processing and higher brain regions. Here we characterize lobula columnar (LC) cells, a class of Drosophila VPNs that project to distinct central brain structures called optic glomeruli. We anatomically describe 22 different LC types and show that, for several types, optogenetic activation in freely moving flies evokes specific behaviors. The activation phenotypes of two LC types closely resemble natural avoidance behaviors triggered by a visual loom. In vivo two-photon calcium imaging reveals that these LC types respond to looming stimuli, while another type does not, but instead responds to the motion of a small object. Activation of LC neurons on only one side of the brain can result in attractive or aversive turning behaviors depending on the cell type. Our results indicate that LC neurons convey information on the presence and location of visual features relevant for specific behaviors. DOI: http://dx.doi.org/10.7554/eLife.21022.001 PMID:28029094

Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease.

PubMed

Karuppagounder, Saravanan S; Pinto, John T; Xu, Hui; Chen, Huan-Lian; Beal, M Flint; Gibson, Gary E

2009-02-01

Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress.

Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile☆

PubMed Central

Skakkebæk, Anne; Gravholt, Claus Højbjerg; Rasmussen, Peter Mondrup; Bojesen, Anders; Jensen, Jens Søndergaard; Fedder, Jens; Laurberg, Peter; Hertz, Jens Michael; Østergaard, John Rosendahl; Pedersen, Anders Degn; Wallentin, Mikkel

2013-01-01

Brain imaging in Klinefelter syndrome (47, XXY) (KS), a genetic disorder characterized by the presence of an extra X chromosome, may contribute to understanding the relationship between gene expression, brain structure, and subsequent cognitive disabilities and psychiatric disorders. We conducted the largest to date voxel-based morphometry study of 65 KS subjects and 65 controls matched for age and education and correlated these data to neuropsychological test scores. The KS patients had significantly smaller total brain volume (TBV), total gray matter volume (GMV) and total white matter volume (WMV) compared to controls, whereas no volumetric difference in cerebral spinal fluid (CSF) was found. There were no differences in TBV, GMV, WMV or CSF between testosterone treated KS (T-KS) and untreated KS (U-KS) patients. Compared to controls, KS patients had significantly decreased GMV bilaterally in insula, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate classification analysis discriminated KS patients from controls with 96.9% (p < 0.001) accuracy. Regression analyses, however, revealed no significant association between GMV differences and cognitive and psychological factors within the KS patients and controls or the groups combined. These results show that although gene dosage effect of having and extra X-chromosome may lead to large scale alterations of brain morphometry and extended cognitive disabilities no simple correspondence links these measures. PMID:24266006

Women are better at seeing faces where there are none: an ERP study of face pareidolia.

PubMed

Proverbio, Alice M; Galli, Jessica

2016-09-01

Event-related potentials (ERPs) were recorded in 26 right-handed students while they detected pictures of animals intermixed with those of familiar objects, faces and faces-in-things (FITs). The face-specific N170 ERP component over the right hemisphere was larger in response to faces and FITs than to objects. The vertex positive potential (VPP) showed a difference in FIT encoding processes between males and females at frontal sites; while for men, the FIT stimuli elicited a VPP of intermediate amplitude (between that for faces and objects), for women, there was no difference in VPP responses to faces or FITs, suggesting a marked anthropomorphization of objects in women. SwLORETA source reconstructions carried out to estimate the intracortical generators of ERPs in the 150-190 ms time window showed how, in the female brain, FIT perception was associated with the activation of brain areas involved in the affective processing of faces (right STS, BA22; posterior cingulate cortex, BA22; and orbitofrontal cortex, BA10) in addition to regions linked to shape processing (left cuneus, BA18/30). Conversely, in the men, the activation of occipito/parietal regions was prevalent, with a considerably smaller activation of BA10. The data suggest that the female brain is more inclined to anthropomorphize perfectly real objects compared to the male brain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Brain structural connectivity and context-dependent extinction memory.

PubMed

Hermann, Andrea; Stark, Rudolf; Blecker, Carlo R; Milad, Mohammed R; Merz, Christian J

2017-08-01

Extinction of conditioned fear represents an important mechanism in the treatment of anxiety disorders. Return of fear after successful extinction or exposure therapy in patients with anxiety disorders might be linked to poor temporal or contextual generalization of extinction due to individual differences in brain structural connectivity. The goal of this magnetic resonance imaging study was therefore to investigate the association of context-dependent extinction recall with brain structural connectivity. Diffusion-tensor imaging was used to determine the fractional anisotropy as a measure of white matter structural integrity of fiber tracts connecting central brain regions of the fear and extinction circuit (uncinate fasciculus, cingulum). Forty-five healthy men participated in a two-day fear conditioning experiment with fear acquisition in context A and extinction learning in context B on the first day. Extinction recall in the extinction context as well as renewal in the acquisition context and a novel context C took place one day later. Renewal of conditioned fear (skin conductance responses) in the acquisition context was associated with higher structural integrity of the hippocampal part of the cingulum. Enhanced structural integrity of the cingulum might be related to stronger hippocampal modulation of the dorsal anterior cingulate cortex, a region important for modulating conditioned fear output by excitatory projections to the amygdala. This finding underpins the crucial role of individual differences in the structural integrity of relevant fiber tracts for context-dependent extinction recall and return of fear after exposure therapy in anxiety disorders. © 2017 Wiley Periodicals, Inc.

Neurobiology of culturally common maternal responses to infant cry

PubMed Central

Bornstein, Marc H.; Rigo, Paola; Esposito, Gianluca; Swain, James E.; Suwalsky, Joan T. D.; Su, Xueyun; Du, Xiaoxia; Zhang, Kaihua; Cote, Linda R.; De Pisapia, Nicola; Venuti, Paola

2017-01-01

This report coordinates assessments of five types of behavioral responses in new mothers to their own infants’ cries with neurobiological responses in new mothers to their own infants’ cries and in experienced mothers and inexperienced nonmothers to infant cries and other emotional and control sounds. We found that 684 new primipara mothers in 11 countries (Argentina, Belgium, Brazil, Cameroon, France, Kenya, Israel, Italy, Japan, South Korea, and the United States) preferentially responded to their infants’ vocalizing distress by picking up and holding and by talking to their infants, as opposed to displaying affection, distracting, or nurturing. Complementary functional magnetic resonance imaging (fMRI) analyses of brain responses to their own infants’ cries in 43 new primipara US mothers revealed enhanced activity in concordant brain territories linked to the intention to move and to speak, to process auditory stimulation, and to caregive [supplementary motor area (SMA), inferior frontal regions, superior temporal regions, midbrain, and striatum]. Further, fMRI brain responses to infant cries in 50 Chinese and Italian mothers replicated, extended, and, through parcellation, refined the results. Brains of inexperienced nonmothers activated differently. Culturally common responses to own infant cry coupled with corresponding fMRI findings to own infant and to generic infant cries identified specific, common, and automatic caregiving reactions in mothers to infant vocal expressions of distress and point to their putative neurobiological bases. Candidate behaviors embedded in the nervous systems of human caregivers lie at the intersection of evolutionary biology and developmental cultural psychology. PMID:29078366

Verbal and non-verbal intelligence changes in the teenage brain.

PubMed

Ramsden, Sue; Richardson, Fiona M; Josse, Goulven; Thomas, Michael S C; Ellis, Caroline; Shakeshaft, Clare; Seghier, Mohamed L; Price, Cathy J

2011-10-19

Intelligence quotient (IQ) is a standardized measure of human intellectual capacity that takes into account a wide range of cognitive skills. IQ is generally considered to be stable across the lifespan, with scores at one time point used to predict educational achievement and employment prospects in later years. Neuroimaging allows us to test whether unexpected longitudinal fluctuations in measured IQ are related to brain development. Here we show that verbal and non-verbal IQ can rise or fall in the teenage years, with these changes in performance validated by their close correlation with changes in local brain structure. A combination of structural and functional imaging showed that verbal IQ changed with grey matter in a region that was activated by speech, whereas non-verbal IQ changed with grey matter in a region that was activated by finger movements. By using longitudinal assessments of the same individuals, we obviated the many sources of variation in brain structure that confound cross-sectional studies. This allowed us to dissociate neural markers for the two types of IQ and to show that general verbal and non-verbal abilities are closely linked to the sensorimotor skills involved in learning. More generally, our results emphasize the possibility that an individual's intellectual capacity relative to their peers can decrease or increase in the teenage years. This would be encouraging to those whose intellectual potential may improve, and would be a warning that early achievers may not maintain their potential.

Readiness to change and brain damage in patients with chronic alcoholism.

PubMed

Le Berre, Anne-Pascale; Rauchs, Géraldine; La Joie, Renaud; Segobin, Shailendra; Mézenge, Florence; Boudehent, Céline; Vabret, François; Viader, Fausto; Eustache, Francis; Pitel, Anne-Lise; Beaunieux, Hélène

2013-09-30

High motivation to change is a crucial triggering factor to patients' engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into "Action" (i.e., patients in action stage) and "PreAction" (i.e., patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply "processes of change", which are essential for activating the desire to change problematic behavior. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Patient-tailored multimodal neuroimaging, visualization and quantification of human intra-cerebral hemorrhage

NASA Astrophysics Data System (ADS)

Goh, Sheng-Yang M.; Irimia, Andrei; Vespa, Paul M.; Van Horn, John D.

2016-03-01

In traumatic brain injury (TBI) and intracerebral hemorrhage (ICH), the heterogeneity of lesion sizes and types necessitates a variety of imaging modalities to acquire a comprehensive perspective on injury extent. Although it is advantageous to combine imaging modalities and to leverage their complementary benefits, there are difficulties in integrating information across imaging types. Thus, it is important that efforts be dedicated to the creation and sustained refinement of resources for multimodal data integration. Here, we propose a novel approach to the integration of neuroimaging data acquired from human patients with TBI/ICH using various modalities; we also demonstrate the integrated use of multimodal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data for TBI analysis based on both visual observations and quantitative metrics. 3D models of healthy-appearing tissues and TBIrelated pathology are generated, both of which are derived from multimodal imaging data. MRI volumes acquired using FLAIR, SWI, and T2 GRE are used to segment pathology. Healthy tissues are segmented using user-supervised tools, and results are visualized using a novel graphical approach called a `connectogram', where brain connectivity information is depicted within a circle of radially aligned elements. Inter-region connectivity and its strength are represented by links of variable opacities drawn between regions, where opacity reflects the percentage longitudinal change in brain connectivity density. Our method for integrating, analyzing and visualizing structural brain changes due to TBI and ICH can promote knowledge extraction and enhance the understanding of mechanisms underlying recovery.