Alterations in Cognition-Related Cerebello-Cerebral Networks in Multiple System Atrophy

We aimed to elucidate the effect of cerebellar degeneration in relation to cognition in multiple system atrophy (MSA). Thirty-two patients diagnosed with probable MSA and 32 age- and gender-matched healthy controls (HCs) were enrolled. We conducted voxel-based morphometry (VBM) for anatomical images and independent component analysis (ICA), dual-regression analysis, and seed-based analysis for functional images with voxel-wise gray matter correction. In the MSA group, a widespread cerebellar volume loss was observed. ICA and dual-regression analysis showed lower functional connectivity (FC) in the left executive control and salience networks in regions located in the cerebellum. Seed-based analysis using the identified cerebellar regions as seeds showed extensive disruptions in cerebello-cerebral networks. Global cognitive scores correlated with the FC values between the right lobules VI/crus I and the medial prefrontal/anterior cingulate cortices and between the same region and the amygdala/parahippocampal gyrus. Our study indicates that cerebellar degeneration in MSA causes segregation of cerebellar-cerebral networks. Furthermore, the cognitive deficits in MSA may be driven by decreased cerebello-prefrontal and cerebello-amygdaloid functional connections.