Objective: The aim of this study was to investigate functional alterations within motor circuits of the cerebro-cerebellar system in tremor-dominant (TD) and postural instability and gait disorder (PIGD) Parkinson’s disease (PD) groups using stepwise functional connectivity (SFC) method.

Background: PD is the most common neurodegenerative movement disorder. PD patients are usually classified as TD and PIGD phenotypes, based on the predominant motor signs.

Method: 58 PD patients performed clinical and cognitive evaluations and resting-state functional MRI (fMRI). PD cohort was divided into two groups: 32 patients with TD (PD-TD) and 26 with PIGD (PD-PIGD). 60 age- and sex-matched healthy controls were also enrolled.SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link-step distances. The cerebellar seed-region was identified using motor task-based fMRI in 23 controls. For each of the SFC maps, whole-brain two-sample t-test comparisons between groups were performed.

Results: The performance of the motor task during fMRI was associated with activation of the lobule VI and vermis of the cerebellum. SFC analysis at one-link step distance showed, in both PD subtypes, a decreased regional-local connectivity between seed region and thalamus and parietal lobe relative to controls; across intermediate link-steps, a reduced connectivity was observed with frontal, parietal and occipital lobes. Only PD-PIGD patients showed lower connectivity at intermediate link-step distances between the seed-cerebellar region and sensorimotor areas. In addition, SFC pattern identified different localization of functional over‐connectivity in frontal lobe in both PD groups: in inferior frontal gyrus and insula in PD-PIGD, and in orbitofrontal gyrus in PD-TD.

Conclusion: Our results suggest that an atypical flow of information from short to long functional distances between cerebellum, thalamus and default-mode regions occurs in both PD clinical variants. These findings highlight subtype-specific PD changes in cerebellar connectivity, providing novel insights into the pathophysiological mechanism potentially underlying different motor phenotypes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-cerebro-cerebellar-networks-breakdown-among-different-subtypes-of-parkinsons-disease/