Objective Neuroanatomical differences in the cerebellum are among the most consistent findings in multiple system atrophy (MSA) patients. This study performed a detailed cerebellar morphology in MSA patients and its two subtypes: MSA-P (parkinson's symptoms predominate) and MSA-C (cerebellar symptoms predominant), and their relations to profiles of motor and cognitive deficits. Materials and methods Structure MRI data were acquired from 63 healthy controls and 61 MSA patients; voxel-based morphometry and the Spatially Unbiased Infratentorial Toolbox cerebellar atlas were performed to identify the cerebellar gray volume changes in MSA and its subtypes. Further, the gray matter changes were correlated with the clinical motor/cognitive scores. Results Patients with MSA exhibited widespread loss of cerebellar volume bilaterally, relative to healthy controls. In those with MSA-C, gray matter loss was detected from anterior (bilateral lobule IV-V) to posterior (bilateral crus I/II, bilateral lobule IX, left lobule VIII) cerebellar lobes. Lower anterior cerebellar volume negatively correlated with disease duration and motor performance, whereas posterior lobe integrity positively correlated with cognitive assessment. In patients with MSA-P, atrophy of anterior lobe (bilateral lobules IV-V) and posterior lobe in part (left lobule VI, bilateral IX) was evident; and in left cerebellar lobule IX, gray matter loss negatively correlated with motor scores. Direct comparison of MSA-P and MSA-C group outcomes showed divergence in right cerebellar crus II only. Conclusions Our data suggest that volumetric abnormalities of cerebellum contribute substantially to motor and cognitive performance in patients with MSA. In patients with MSA-P and MSA-C, affected regions of cerebellum differed.

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Background It is yet unknown if the whole-brain resting-state network is altered in multiple system atrophy with symptoms of depression. This study aimed to investigate if and how depression symptoms in multiple system atrophy are associated with resting-state network dysfunction. Methods We assessed the resting-state functional network matric using Degree centrality (DC) coupling with a second ROI-wise functional connectivity (FC) algorithm in a multimodal imaging case-control study that enrolled 32 multiple system atrophy patients with depression symptoms (MSA-D), 30 multiple system atrophy patients without depression symptoms (MSA-ND), and 34 healthy controls (HC). Results Compared to HC, MSA-D showed more extensive DC hub dysfunction in the left precentral and right middle frontal cortex than MSA-ND. A direct comparison between MSA-D and MSA-ND detected increased DC in the right anterior cingulum cortex, but decreased DC in the left cerebellum lobule IV and lobule V, left middle pole temporal cortex, and right superior frontal cortex. Only right anterior cingulum cortex mean DC values showed a positive correlation with depression severity, and used ACC as seed, a second ROI-wise functional connectivity further revealed MSA-D patients showed decreased connectivity between the ACC and right thalamus and right middle temporal gyrus (MTG). Conclusions These findings revealed that dysfunction of rACC, right middle temporal lobe and right thalamus involved in depressed MSA. Our study might help to the understanding of the neuropathological mechanism of depression in MSA.