Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

William C Palmer,Thomas J Montine,Cyrus P Zabetian,Brenna A Cholerton,Thomas J Grabowski,Swati Rane

doi:10.3389/fneur.2020.594213

Abstract

Purpose: Recently, the cerebellum's role in Parkinson's disease (PD) has been highlighted. Therefore, this study sought to test the hypothesis that functional connectivity (FC) between cerebellar and cortical nodes of the resting-state networks differentiates PD patients from controls by scanning participants at rest using functional magnetic resonance imaging (fMRI) and investigating connectivity of the cerebellar nodes of the resting-state networks.Materials and Methods: Sixty-two PD participants off medication for at least 12 h and 33 normal controls (NCs) were scanned at rest using blood oxygenation level-dependent fMRI scans. Motor and cognitive functions were assessed with the Movement Disorder Society's Revision of the Unified Parkinson's Disease Rating Scale III and Montreal Cognitive Assessment, respectively. Connectivity was investigated with cerebellar seeds defined by Buckner's 7-network atlas.Results: PD participants had significant differences in FC when compared to NC participants. Most notably, PD patients had higher FC between cerebellar nodes of the somatomotor network (SMN) and the corresponding cortical nodes. Cognitive functioning was differentially associated with connectivity of the cerebellar SMN and dorsal attention network. Further, cerebellar connectivity of frontoparietal and default mode networks correlated with the severity of motor function.Conclusion: Our study demonstrates altered cerebello-cortical FC in PD, as well as an association of this FC with PD-related motor and cognitive disruptions, thus providing additional evidence for the cerebellum's role in PD.

Highlights

Parkinson’s disease (PD), a common progressive neurodegenerative disorder, is characterized primarily by motor symptoms and has cognitive symptoms
All participants underwent a full neuropsychological battery [including the Montreal Cognitive Assessment (MoCA)], a neurological examination, and the MDS-UPDRS III. Data from these assessments were reviewed at a diagnostic consensus conference, attended by at least two movement disorders neurologists and a neuropsychologist, to determine the diagnostic category [PD or normal control (NC)] and cognitive status [normal, mild cognitive impairment (MCI), dementia]
In order to ensure that the functional connectivity (FC) differences exist despite the gray matter (GM) atrophy, the GM probabilities were included as a nuisance regressor in all subsequent analyses

Summary

Introduction

Parkinson’s disease (PD), a common progressive neurodegenerative disorder, is characterized primarily by motor symptoms and has cognitive symptoms. PD traditionally has three pathological hallmarks [1]. The first is the progressive loss of dopaminergic neurons in the substantia nigra. The result of nigral neuronal death is a marked depletion of dopamine in the striatum, which has been the principal target for treatment. PD is indicated by the presence of Lewy bodies, composed of α-synuclein aggregates, in the nigra and other subcortical and cortical regions. Neuroimaging studies have played a critical role in our understanding of how Cerebello-Cortical Dysfunction in Parkinson’s Disease these trademark pathologies influence neuronal function in humans [2]. Most studies have focused on the cortex, even though the cerebellum has been implicated in the disease state of PD [3]

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Discussion

Conclusion