Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

• Published in: NeuroImage clinical 2014-01, Vol.5 (C), p.298-308
• Main Authors: Damaraju, E, Allen, E A, Belger, A, Ford, J M, McEwen, S, Mathalon, D H, Mueller, B A, Pearlson, G D, Potkin, S G, Preda, A, Turner, J A, Vaidya, J G, van Erp, T G, Calhoun, V D
• Format: Article
• Language: English
• Subjects: Adult; Brain - physiopathology; Brain Mapping; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Neural Pathways - physiopathology; Schizophrenia - physiopathology
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2014.07.003

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-c