Altered Spinal Cord Functional Connectivity Associated with Parkinson's Disease Progression.

Abstract

Parkinson's disease (PD) has traditionally been viewed as an α-synucleinopathy brain pathology. Yet evidence based on postmortem human and animal experimental models indicates that the spinal cord may also be affected. Functional magnetic resonance imaging (fMRI) seems to be a promising candidate to better characterize spinal cord functional organization in PD patients. Resting-state spinal fMRI was performed in 70 PD patients and 24 age-matched healthy controls, the patients being divided into three groups based on their motor symptom severity: PDlow (n=24), PDmed (n=22), and PDadv (n=24) groups. A combination of independent component analysis (ICA) and a seed-based approach was applied. When pooling all participants, the ICA revealed distinct ventral and dorsal components distributed along the rostro-caudal axis. This organization was highly reproducible within subgroups of patients and controls. PD severity, assessed by Unified Parkinson's Disease Rating Scale (UPDRS) scores, was associated with a decrease in spinal functional connectivity (FC). Notably, we observed a reduced intersegmental correlation in PD as compared to controls, the latter being negatively associated with patients' upper-limb UPDRS scores (P=0.0085). This negative association between FC and upper-limb UPDRS scores was significant between adjacent C4-C5 (P=0.015) and C5-C6 (P=0.20) cervical segments, levels associated with upper-limb functions. The present study provides the first evidence of spinal cord FC changes in PD and opens new avenues for the effective diagnosis and therapeutic strategies in PD. This underscores how spinal cord fMRI can serve as a powerful tool to characterize, in vivo, spinal circuits for a variety of neurological diseases. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.