Interactions between the cortical midline structures and sensorimotor network track maladaptive self-beliefs in clinical high risk for psychosis

Abstract Individuals at clinical high risk for psychosis (CHR) report a maladaptive self-concept—with more negative and less positive self-beliefs—linked to clinical symptoms and functional impairment. Alterations have also been reported in brain networks associated with intrinsic (cortical midline structures, CMS) and extrinsic (sensorimotor network, SMN) self-processing. Theoretical accounts of multiple levels of self-experience in schizophrenia suggest that interactions between these networks would be relevant for self-beliefs. This study tested whether self-beliefs related to resting-state functional connectivity within and between the CMS and SMN. Participants were 56 individuals meeting CHR criteria and 59 matched healthy community participants (HC). Pearson correlations examined potential mediators and outcomes. The CHR group reported more negative and less positive self-beliefs. Greater resting-state functional connectivity between the posterior CMS (posterior cingulate cortex) and the SMN was associated with less positive self-beliefs in CHR, but more positive self-beliefs in HC. Attenuated negative symptoms and poorer social functioning were associated with CMS-SMN connectivity (trend level after FDR-correction) and self-beliefs. Reduced connectivity between the left and right PCC was associated with lower positive self-beliefs in CHR, although this effect was specific to very low levels of positive self-beliefs. Left-right PCC connectivity did not correlate with outcomes. Dynamic interactions between intrinsic and extrinsic self-processing supported positive self-beliefs in typically developing youth while undermining positive self-beliefs in CHR youth. Implications are discussed for basic self-fragmentation, narrative self-related metacognition, and global belief updating. Interventions for self-processing may be beneficial in the CHR syndrome.