Aims

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

Methods

32 PD-TD and 26 PD-PIGD patients performed clinical/cognitive evaluations and resting-state functional MRI (fMRI). 60 age- and sex-matched 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 in 23 controls. For each of the SFC maps, two-sample t-test comparisons between groups were performed.

Results

The performance of the fMRI-motor task 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 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. Moreover, SFC pattern identified different localization of functional over‐connectivity in frontal lobe in both PD groups: inferior frontal gyrus and insula in PD-PIGD, and in orbitofrontal gyrus in PD-TD.

Conclusions

These findings highlight subtype-specific PD changes in cerebellar functional connectivity, providing novel insights into the pathophysiological mechanism underlying different motor phenotypes.

Funding: Ministry of Education and Science Republic of Serbia (#175090), Italian Ministry of Health (#RF-2018-12366746).