Pons-to-cerebellum hypoconnectivity along the psychosis spectrum and associations with sensory prediction and hallucinations in schizophrenia

Background Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally-generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). Pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. Methods We examined these relationships using resting-state fMRI and electroencephalography-based auditory N1 event-related potential in 143 psychotic-spectrum disorder participants (PSP with schizophrenia, schizoaffective, or bipolar disorder), 63 first-degree relatives of individuals with psychosis (REL), 45 people at clinical high-risk for psychosis (CHR-P), and 124 unaffected comparison participants (UCP). This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing PSP versus UCP differences. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level PSP and CHR-P connectivity with hallucination and delusion severity. Results Compared to UCP, PSP showed pons hypoconnectivity to two cerebellar clusters, and REL showed hypoconnectivity to one of these clusters. Pons-to-cerebellum connectivity positively correlated with N1 attenuation; only PSP with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity correlated with greater hallucinations specifically among PSP with schizophrenia. Conclusions Deficient pons-to-cerebellum connectivity links sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.