Altered Functional and Causal Connectivity of Cerebello-Cortical Circuits between Multiple System Atrophy (Parkinsonian Type) and Parkinson’s Disease

Lesions of the cerebellum lead to motor and non-motor deficits by influencing cerebral cortex activity via cerebello-cortical circuits. It remains unknown whether the cerebello-cortical "disconnection" underlies motor and non-motor impairments both in the parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). In this study, we investigated both the functional and effective connectivity of the cerebello-cortical circuits from resting-state functional magnetic resonance imaging (rs-fMRI) data of three groups (26 MSA-P patients, 31 PD patients, and 30 controls). Correlation analysis was performed between the causal connectivity and clinical scores. PD patients showed a weakened cerebellar dentate nucleus (DN) functional coupling in the posterior cingulate cortex (PCC) and inferior parietal lobe compared with MSA-P or controls. MSA-P patients exhibited significantly enhanced effective connectivity from the DN to PCC compared with PD patients or controls, as well as declined causal connectivity from the left precentral gyrus to right DN compared with the controls, and this value is significantly correlated with the motor symptom scores. Our findings demonstrated a crucial role for the cerebello-cortical networks in both MSA-P and PD patients in addition to striatal-thalamo-cortical (STC) networks and indicated that different patterns of cerebello-cortical loop degeneration are involved in the development of the diseases.