Cerebello-Basal Ganglia Functional Network Integration in Psychosis

Abstract

Psychotic disorders are conceptualized as brain-network diseases and both the cerebellum (CB) and basal ganglia (BG) are implicated in widely used conceptual models. Previous research has focused on these structures and their respective circuits as distinct, however, both are functionally and anatomically connected to each other and to cortical networks via domain-specific, topographically organized thalamo-cortical loops. Currently, it is unclear how CB-BG network dysfunction may play a mechanistic role in the course of psychosis; however, network global efficiency (GE), a measure of functional integration, is a novel approach that aims to represent cognitive and motor CB-BG network (CCBN, MCBN, respectively) connectivity in cross- sectional groups of healthy control (HC), clinical high-risk (CHR), early course psychosis (ECP), and chronic psychosis (CP) participants. We compared network GE between groups and inspected individual differences in CCBN- and MCBN-GE as it relates to group membership and to psychosis symptoms. We also associated CB-BG network GE with cortical network GE. Results indicated that CCBN-GE was associated with cognitive dysfunction and lower in CHR individuals, compared to HC and CP; while MCBN was associated with negative psychosis symptoms. Last, we detailed CB-BG associations with sensory, motor, default mode, and salience networks across groups, with group effects demonstrating complex differences within the ECP group. Findings indicating that CB-BG network dysfunction may play an important role in early pathogenesis and authors argue for CB-BG dysfunction to be analyzed from a network perspective. Future work is needed however to incorporate this approach into our understanding of psychosis.