Cortical Functional Connectivity Changes in the Body-First and Brain-First Subtypes of Parkinson's Disease

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) may precede motor symptoms in Parkinson's disease (PD) by years. According to a recent hypothesis, premotor RBD (pRBD) is a marker of the PD body-first subtype, where synucleinopathy originates from the peripheral autonomic nervous system. Conversely, in the brain-first subtype, pathology would arise in the brain. Functional connectivity (FC) could provide additional insight into the neurodegenerative process of these putative PD subtypes. Objectives We aim to analyze the possible FC differences between early-stage PD patients with (PDpRBD+) and without (PDpRBD-) pRBD using high-density electroencephalography (EEG). Methods We enrolled 28 PDpRBD+, 35 PDpRBD-, and 35 healthy controls (HC). Data were recorded with a 64-channel EEG system, and a source-reconstruction method was used to identify brain-region activity. FC was calculated using the weighted phase-lag index in theta, alpha, beta, and low-gamma bands. Statistical analysis was conducted using network-based statistic. Results We found a significant trend of decreased alpha-FC across PDpRBD+, PDpRBD-, and HC, mainly in prefrontal and temporal areas. The altered alpha-FC correlated with Montreal Cognitive Assessment scores in PDpRBD+ and, to a lesser extent, PDpRBD- and with gait/postural disturbances in PDpRBD+ patients only. PDpRBD+ and PDpRBD- had similarly increased FC than HC in a beta band network, predominantly involving sensorimotor and limbic areas. The increased beta network FC was related to bradykinesia severity in both PD subgroups. Conclusions Compared to PDpRBD- (brain-first subtype), PDpRBD+ group (body-first subtype) demonstrates specific EEG-FC dysfunctions in the alpha band, which may reflect early involvement of the cholinergic ascending system. (c) 2024 International Parkinson and Movement Disorder Society.