Objective: to investigate whether PD patients carrying pathogenetic GBA variants exhibit distinct frequency-specific EEG-based FC alterations compared with GBA1-negative PD patients (PD-GBA−).
Background: Variants in the GBA1 gene are the strongest genetic risk factors for Parkinson’s disease (PD) and are associated with a more severe clinical phenotype, characterized by earlier gait impairment, cognitive decline, and faster development of motor complications [1]. While these features suggest a distinct network-level vulnerability, the functional connectivity (FC) correlates of GBA-associated PD (PD-GBA+) remain scarcely understood.
Method: 60 PD patients, including 30 GBA variant carriers (PD-GBA+) and 30 genetically negative patients (PD-GBA−), and 30 healthy controls (HC) were enrolled. Resting-state EEG was recorded using a 64-channel HD-EEG system. Source reconstruction was performed using an individual brain MRI to estimate regional cortical activity. Cortico-cortical FC was computed using the weighted phase-lag index in theta, alpha, beta, low, and high-gamma frequency bands [2]. Group differences in FC were assessed using Network-Based Statistics, and network-level FC measures were correlated with clinical scores.
Results: In the beta band, a significant between-group network difference was observed, showing an increase in FC across the spectrum HC<PD-GBA-<PD-GBA+. This network primarily involved sensorimotor and parietal regions, and mean network connectivity was positively associated with bradykinesia. In the high-gamma band, the analysis detected a network showing reduced FC in PD-GBA+ compared with PD-GBA- patients, predominantly encompassing prefrontal and sensorimotor nodes. Lower FC in the high-gamma band was significantly associated with greater motor complication severity in both PD groups.
Conclusion: Our findings reveal peculiar frequency-specific network alterations in PD-GBA+. Increased beta FC may suggest maladaptive motor network synchronization, functionally related to bradykinesia severity. Reduced high-gamma FC may reflect impaired fast cortico-cortical communication, potentially underlying the earlier development of motor fluctuations observed in the PD-GBA+. EEG-based FC may therefore represent a non-invasive tool to capture genotype-specific brain network vulnerability in PD.
References: [1] S. Petrucci et al., “
[2] M. Conti et al., “Cortical Functional Connectivity Changes in the Body‐First and Brain‐First Subtypes of Parkinson’s Disease,” Movement Disorders, vol. 40, no. 2, pp. 254–265, Feb. 2025, doi: 10.1002/mds.30071.
To cite this abstract in AMA style:
M. Conti, V. D'Onofrio, M. Avenali, L. Lorenzon, L. Grassi, M. Ginevrino, L. Salviati, M. Terzaghi, M. Carecchio, A. Stefani, EM. Valente, A. Antonini, A. Guerra. EEG-based Functional Connectivity Reveals a Genotype-Specific Network Signature in GBA-Associated Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/eeg-based-functional-connectivity-reveals-a-genotype-specific-network-signature-in-gba-associated-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/eeg-based-functional-connectivity-reveals-a-genotype-specific-network-signature-in-gba-associated-parkinsons-disease/