Abstract
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.
Highlights
Schizophrenia is a complex brain disorder of unknown etiology
We demonstrated that participants with schizophrenia had significantly lower fractional anisotropy (FA) in the MCP than did healthy controls (HCs) and showed an inverse correlation between FAs in the MCP and performance in executive function measured by the TMT-B and Wisconsin Card Sorting Test (WCST)
Our findings suggest that white matter (WM) dysconnectivity in afferent fibers from the cerebrum to the cerebellum may be associated with impaired cognitive function in patients with schizophrenia, which is consistent with the notion of cognitive dysmetria
Summary
Schizophrenia is a complex brain disorder of unknown etiology. Neurobiological models of schizophrenia have focused on structural and functional abnormalities in the cerebrum, the fronto-temporo-limbic areas[1,2]; the understanding of schizophrenia remains unsatisfactory because none of the proposed models fully explain its pathogenetic mechanisms. In higher-order cognitive function, the cerebellum has been suggested to parallel its role in the fine control of motor movements to regulate the speed, balance, coordination, and accuracy[8] This is supported by early reports describing impairments to executive function, visuospatial organization, and language processing, as well as inappropriate effect and behavior in patients with acquired lesions in the cerebellum[9]. These cognitive-affective symptoms overlap with those observed in patients with schizophrenia, implying the possible involvement of the cerebellum in the development of schizophrenia
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