Cortical functional connectivity changes in the body-first and brain-first subtypes of Parkinson's disease

Background: Rapid 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 θ, α, β, and low-γ bands. Statistical analysis was conducted using network-based statistic. Results: We found a significant trend of decreased α-FC across PDpRBD+, PDpRBD−, and HC, mainly in prefrontal and temporal areas. The altered α-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 β band network, predominantly involving sensorimotor and limbic areas. The increased β 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 α band, which may reflect early involvement of the cholinergic ascending system. © 2024 International Parkinson and Movement Disorder Society.