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 (PD) and without (PD) pRBD using high-density electroencephalography (EEG).

Methods: We enrolled 28 PD, 35 PD, 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 PD, PD, and HC, mainly in prefrontal and temporal areas. The altered α-FC correlated with Montreal Cognitive Assessment scores in PD and, to a lesser extent, PD and with gait/postural disturbances in PD patients only. PD and PD 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 PD (brain-first subtype), PD 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.