Alterations of cerebellar white matter integrity and associations with cognitive impairments in schizophrenia

Abstract

“Cognitive dysmetria” theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.