ABSTRACT
Distributed neural dysconnectivity is considered a hallmark feature of schizophrenia, yet a tension exists between studies pinpointing focal disruptions versus those implicating brain-wide disturbances. The cerebellum and the striatum communicate reciprocally with the thalamus and cerebral cortex through monosynaptic and polysynaptic connections, forming cortico-striatal-thalamic-cerebellar (CSTC) functional pathways that may be sensitive to brain-wide dysconnectivity in schizophrenia. It remains unknown if the same brain-wide pattern of alterations persists across CSTC systems, or if specific alterations exist along key functional elements of these networks. We characterized whole-brain cerebellar and striatal connectivity using resting-state functional magnetic resonance imaging in 159 chronic schizophrenia patients and 162 matched controls, along each major cerebellar and striatal functional subdivision. Both cerebellar and striatal associative subdivisions revealed consistent brain-wide bi-directional alterations in patients relative to controls, marked by hyper-connectivity with bilateral sensory-motor cortices and hypo-connectivity with association cortex. These results implicate a consistent motif of brain-wide alterations in cortico-striato-cerebellar systems in schizophrenia, calling into question accounts of exclusively focal functional connectivity disturbances.