Aberrant cerebro-cerebellar functional connectivity and minimal self-disturbance in individuals at ultra-high risk for psychosis and with first-episode schizophrenia

BACKGROUND: In the tradition of phenomenology, minimal selfdisturbance has been suggested as a manifestation of the core pathogenesis of schizophrenia; however, the underlying neural mechanism remains unclear. Here, in line with the concept of "cognitive dysmetria," we investigated the cerebro-cerebellar default mode network (DMN) connectivity and its association with pre-reflective minimal selfdisturbance in individuals at ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia (FES).

METHODS: Thirty-three UHR individuals, 18 FES patients, and 56 healthy controls (HCs) underwent functional magnetic resonance imaging during rest at baseline. Seed-based functional connectivity (FC) analysis was performed using the cerebellar DMN seeds from the bilateral Crus I, followed by between-group comparisons. Correlation analysis was conducted to examine the relationship between the cerebro-cerebellar FC and the self-reported severity of minimal self-disturbance in the UHR and FES groups, respectively.

RESULTS: FES participants showed significantly reduced cerebellar FC with the left presupplementary motor area (preSMA), right anterior prefrontal cortex (aPFC), and precuneus compared to HCs, while UHR participants showed an intermediate decrease between the other two groups, particularly in the left preSMA and right aPFC. Minimal self-disturbance, which appeared at similar levels in both UHR and FES groups, was significantly associated with cerebro-cerebellar FC, although each group presented different patterns of associations.

CONCLUSIONS: Aberrant cerebro-cerebellar FC, which may be closely related to minimal self-disturbance, may be able to provide meaningful insights into the real gestalt of schizophrenia and contribute to further research to predict future psychosis in UHR individuals.