Disrupted cerebellar interactions in the cerebellar-thalamo-cortical triple network model across risk states and first-episode psychosis

Cerebellar dysconnectivity has been repeatedly linked to psychosis and is often accompanied by disruptions in thalamic and cortical regions. These disturbances are broadly consistent with the triple network model, which conceptualizes psychopathology as arising from abnormal interactions among the salience (SAL), default mode (DMN), and executive control (ECN) networks. However, how the cerebellum interacts with thalamic and cortical components of these networks across different psychosis risk stages and early psychosis remains unclear. Resting-state functional MRI from 37 first-episode psychosis (FEP) patients, 63 clinical high-risk (CHR) individuals, 41 unaffected relatives (URs) of schizophrenia patients, and 100 healthy controls (HCs) were analyzed. The cerebellum and thalamus were parcellated according to their functional connectivity with cortical functional networks, and the DMN, SAL, and ECN subdivisions across all three regions were used to estimate cerebellar-cortical and cerebellar-thalamic connectivity across groups. Compared with HCs, FEP patients showed widespread increases in cerebellar-cortical connectivity across all three networks, together with reduced cerebellar-thalamic connectivity, most prominently within SAL-related circuits. CHR individuals exhibited predominantly increased connectivity, with localized disruptions across cerebellar, thalamic, and cortical regions. URs did not show significant connectivity differences relative to HCs. By extending the triple network framework to include cortico-thalamo-cerebellar pathways, this study characterized how cerebellar network connectivity differs across familial risk, CHR, and FEP groups. The observed pattern suggests that early changes in CTC circuits correspond to disruptions described within the triple network model, and highlights the potential relevance of cerebellar and thalamic involvement when characterizing network alterations across the psychosis spectrum.