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. 2025 Feb;40(2):254-265.
doi: 10.1002/mds.30071. Epub 2024 Nov 29.

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

Matteo Conti  1 , Valentina D'Onofrio  2 , Roberta Bovenzi  1 , Valerio Ferrari  1 , Francesca Di Giuliano  3 , Rocco Cerroni  1 , Mariangela Pierantozzi  1   4 , Tommaso Schirinzi  1   4 , Nicola Biagio Mercuri  1 , Angelo Antonini  2   5 , Andrea Guerra  2   5 , Alessandro Stefani  1   4
Affiliations

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

Matteo Conti et al. Mov Disord. 2025 Feb.

Abstract

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.

Keywords: HD‐EEG; Parkinson's disease; functional connectivity; premotor RBD.

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