Dataset Information

Graph-theoretical analysis identifies transient spatial states of resting-state dynamic functional network connectivity and reveals dysconnectivity in schizophrenia.

ABSTRACT:

Background

Dynamic functional network connectivity (dFNC) summarizes associations among time-varying brain networks and is widely used for studying dynamics. However, most previous studies compute dFNC using temporal variability while spatial variability started receiving increasing attention. It is hence desirable to investigate spatial variability and the interaction between temporal and spatial variability.

New method

We propose to use an adaptive variant of constrained independent vector analysis to simultaneously capture temporal and spatial variability, and introduce a goal-driven scheme for addressing a key challenge in dFNC analysis---determining the number of transient states. We apply our methods to resting-state functional magnetic resonance imaging data of schizophrenia patients (SZs) and healthy controls (HCs).

Results

The results show spatial variability provides more features discriminative between groups than temporal variability. A comprehensive study of graph-theoretical (GT) metrics determines the optimal number of spatial states and suggests centrality as a key metric. Four networks yield significantly different levels of involvement in SZs and HCs. The high involvement of a component that relates to multiple distributed brain regions highlights dysconnectivity in SZ. One frontoparietal component and one frontal component demonstrate higher involvement in HCs, suggesting a more efficient cognitive control system relative to SZs.

Comparison with existing methods

Spatial variability is more informative than temporal variability. The proposed goal-driven scheme determines the optimal number of states in a more interpretable way by making use of discriminative features.

Conclusion

GT analysis is promising in dFNC analysis as it identifies distinctive transient spatial states of dFNC and reveals unique biomedical patterns in SZs.

SUBMITTER: Long Q

PROVIDER: S-EPMC8026655 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Graph-theoretical analysis identifies transient spatial states of resting-state dynamic functional network connectivity and reveals dysconnectivity in schizophrenia.

Long Qunfang Q Bhinge Suchita S Calhoun Vince D VD Adali Tülay T

Journal of neuroscience methods 20201225

<h4>Background</h4>Dynamic functional network connectivity (dFNC) summarizes associations among time-varying brain networks and is widely used for studying dynamics. However, most previous studies compute dFNC using temporal variability while spatial variability started receiving increasing attention. It is hence desirable to investigate spatial variability and the interaction between temporal and spatial variability.<h4>New method</h4>We propose to use an adaptive variant of constrained indepen ...[more]

PMID: 33370561

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Project description:Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Project description:Interhemispheric connectivity with resting state MEG has been elusive, and demonstration of the default mode network (DMN) yet more challenging. Recent seed-based MEG analyses have shown interhemispheric connectivity using power envelope correlations. The purpose of this study is to compare graph theoretic maps of brain connectivity generated using MEG with and without signal leakage correction to evaluate for the presence of interhemispheric connectivity. Eight minutes of resting state eyes-open MEG data were obtained in 22 normal male subjects enrolled in an IRB-approved study (ages 16-18). Data were processed using an in-house automated MEG processing pipeline and projected into standard (MNI) source space at 7mm resolution using a scalar beamformer. Mean beta-band amplitude was sampled at 2.5second epochs from the source space time series. Leakage correction was performed in the time domain of the source space beam formed signal prior to amplitude transformation. Graph theoretic voxel-wise source space correlation connectivity analysis was performed for leakage corrected and uncorrected data. Degree maps were thresholded across subjects for the top 20% of connected nodes to identify hubs. Additional degree maps for sensory, visual, motor, and temporal regions were generated to identify interhemispheric connectivity using laterality indices. Hubs for the uncorrected MEG networks were predominantly symmetric and midline, bearing some resemblance to fMRI networks. These included the cingulate cortex, bilateral inferior frontal lobes, bilateral hippocampal formations and bilateral cerebellar hemispheres. These uncorrected networks however, demonstrated little to no interhemispheric connectivity using the ROI-based degree maps. Leakage corrected MEG data identified the DMN, with hubs in the posterior cingulate and biparietal areas. These corrected networks demonstrated robust interhemispheric connectivity for the ROI-based degree maps. Graph theoretic analysis of MEG resting state data without signal leakage correction can demonstrate symmetric networks with some resemblance to fMRI networks. These networks however, are an artifact of high local correlation from signal leakage and lack interhemispheric connectivity. Following signal leakage correction, MEG hubs emerge in the DMN, with strong interhemispheric connectivity.

Dataset Information

Graph-theoretical analysis identifies transient spatial states of resting-state dynamic functional network connectivity and reveals dysconnectivity in schizophrenia.

Background

New method

Results

Comparison with existing methods

Conclusion

Publications

Graph-theoretical analysis identifies transient spatial states of resting-state dynamic functional network connectivity and reveals dysconnectivity in schizophrenia.

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