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Intra- and inter-frequency brain network structure in health and schizophrenia.

ABSTRACT: Empirical studies over the past two decades have provided support for the hypothesis that schizophrenia is characterized by altered connectivity patterns in functional brain networks. These alterations have been proposed as genetically mediated diagnostic biomarkers and are thought to underlie altered cognitive functions such as working memory. However, the nature of this dysconnectivity remains far from understood. In this study, we perform an extensive analysis of functional connectivity patterns extracted from MEG data in 14 subjects with schizophrenia and 14 healthy controls during a 2-back working memory task. We investigate uni-, bi- and multivariate properties of sensor time series by computing wavelet entropy of and correlation between time series, and by constructing binary networks of functional connectivity both within and between classical frequency bands ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]). Networks are based on the mutual information between wavelet time series, and estimated for each trial window separately, enabling us to consider both network topology and network dynamics. We observed significant decreases in time series entropy and significant increases in functional connectivity in the schizophrenia group in comparison to the healthy controls and identified an inverse relationship between these measures across both subjects and sensors that varied over frequency bands and was more pronounced in controls than in patients. The topological organization of connectivity was altered in schizophrenia specifically in high frequency [Formula: see text] and [Formula: see text] band networks as well as in the [Formula: see text]-[Formula: see text] cross-frequency networks. Network topology varied over trials to a greater extent in patients than in controls, suggesting disease-associated alterations in dynamic network properties of brain function. Our results identify signatures of aberrant neurophysiological behavior in schizophrenia across uni-, bi- and multivariate scales and lay the groundwork for further clinical studies that might lead to the discovery of new intermediate phenotypes.

SUBMITTER: Siebenhuhner F

PROVIDER: S-EPMC3753323 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Intra- and inter-frequency brain network structure in health and schizophrenia.

Siebenhühner Felix F Weiss Shennan A SA Coppola Richard R Weinberger Daniel R DR Bassett Danielle S DS

PloS one 20130826 8

Empirical studies over the past two decades have provided support for the hypothesis that schizophrenia is characterized by altered connectivity patterns in functional brain networks. These alterations have been proposed as genetically mediated diagnostic biomarkers and are thought to underlie altered cognitive functions such as working memory. However, the nature of this dysconnectivity remains far from understood. In this study, we perform an extensive analysis of functional connectivity patte ...[more]

PMID: 23991097

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Project description:Examination of intrinsic functional connectivity using functional MRI (fMRI) has provided important findings regarding dysconnectivity in schizophrenia. Extending these results using a complementary neuroimaging modality, magnetoencephalography (MEG), we present the first direct comparison of functional connectivity between schizophrenia patients and controls, using these two modalities combined. We developed a novel MEG approach for estimation of networks using MEG that incorporates spatial independent component analysis (ICA) and pairwise correlations between independent component timecourses, to estimate intra- and intern-network connectivity. This analysis enables group-level inference and testing of between-group differences. Resting state MEG and fMRI data were acquired from a large sample of healthy controls (n=45) and schizophrenia patients (n=46). Group spatial ICA was performed on fMRI and MEG data to extract intrinsic fMRI and MEG networks and to compensate for signal leakage in MEG. Similar, but not identical spatial independent components were detected for MEG and fMRI. Analysis of functional network connectivity (FNC; i.e., pairwise correlations in network (ICA component) timecourses) revealed a differential between-modalities pattern, with greater connectivity among occipital networks in fMRI and among frontal networks in MEG. Most importantly, significant differences between controls and patients were observed in both modalities. MEG FNC results in particular indicated dysfunctional hyperconnectivity within frontal and temporal networks in patients, while in fMRI FNC was always greater for controls than for patients. This is the first study to apply group spatial ICA as an approach to leakage correction, and as such our results may be biased by spatial leakage effects. Results suggest that combining these two neuroimaging modalities reveals additional disease-relevant patterns of connectivity that were not detectable with fMRI or MEG alone.

Project description:Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity.Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability.The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise.

Project description:BackgroundRifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well.MethodsTwenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed.ResultsAfter rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers.ConclusionsThere was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.

Dataset Information

Intra- and inter-frequency brain network structure in health and schizophrenia.

Publications

Intra- and inter-frequency brain network structure in health and schizophrenia.

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