Objective: To investigate the neurophysiological basis of Parkinson’s disease (PD) in patients with glucocerebrosidase (GBA) mutations.

Background: Alterations in subthalamic neural activity are associated with PD symptoms and can be modulated with deep brain stimulation (DBS). Mutations in GBA gene influence PD symptomatology and may impact DBS clinical outcome. We hypothesized that GBA mutations alter neural activity, contributing to distinct clinical features.

Method: We compared the neural activity of idiopathic and GBA-mutated PD patients undergoing DBS. We retrospectively analyzed bilateral intraoperative microelectrode recordings from 14 PD patients with pathogenic GBA mutations and compared them with recordings from 28 genetically negative PD patients. We assessed spiking activity and oscillations in neurons of the subthalamic nucleus (STN) and substantia nigra (SNr).

Results: GBA-mutated patients showed distinctive STN neural activity. Bursty STN neurons in GBA-mutated patients exhibited a higher firing rate and increased oscillatory activity in the high-beta frequency range (21–35 Hz) compared to idiopathic PD patients. These neural activity changes correlated with DBS clinical outcome. SNr neural activity also differed between GBA-mutated and idiopathic PD patients.

Conclusion: Our findings reveal distinct neural activity patterns in GBA-mutated PD patients, providing the first neurophysiological evidence of their clinical differences.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/gba-mutations-alter-subthalamic-and-nigral-neural-activity-in-parkinsons-disease/