Dynamic functional connectivity impairments in early schizophrenia and clinical high-risk for psychosis

Abstract

Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations.

Keywords: Clinical high-risk; Connectivity state; Dynamic functional connectivity; ICA; Schizophrenia; fMRI.