Impaired cerebro-cerebellar white matter connectivity and its associations with cognitive function in patients with schizophrenia

Schizophrenia is a complex brain disorder of unknown etiology. Based on the notion of “cognitive dysmetria,” we aimed to investigate aberrations in structural white matter (WM) connectivity that links the cerebellum to cognitive dysfunction in patients with schizophrenia. A total of 112 participants (65 patients with schizophrenia and 47 healthy controls [HCs]) were enrolled and underwent diffusion tensor imaging. Between-group voxel-wise comparisons of cerebellar WM regions (superior/middle [MCP]/inferior cerebellar peduncle and pontine crossing fibers) were performed using Tract-Based Spatial Statistics. Cognitive function was assessed using the Trail Making Test Part A/B (TMT-A/B), Wisconsin Card Sorting Test (WCST), and Rey-Kim Memory Test in 46 participants with schizophrenia. WM connectivity, measured as fractional anisotropy (FA), was significantly lower in the MCP in participants with schizophrenia than in HCs. The mean FAs extracted from the significant MCP cluster were inversely correlated with poorer cognitive performance, particularly longer time to complete the TMB-B (r = 0.559, p < 0.001) and more total errors in the WCST (r = 0.442, p = 0.003). Our findings suggest that aberrant cerebro-cerebellar communication due to disrupted WM connectivity may contribute to cognitive impairments, a core characteristic of schizophrenia. Our results may expand our understanding of the neurobiology of schizophrenia based on the cerebro-cerebellar interconnectivity of the brain.