A Convergent Pathway for Stimulation-Induced Dyskinesia Following Deep Brain Stimulation

Abstract

Background: Stimulation-induced dyskinesias (SID) from deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are uncommon; however, they are increasingly recognized. Once considered transient and indicative of effective neuromodulation, SID are now seen as potential therapy-limiting side effects, akin to internal capsule activation. The mechanism and anatomical basis for SID remain poorly understood. Methods: We conducted a retrospective study of individuals with Parkinson's disease with STN or GPi DBS who experienced SID in the dopaminergic medication OFF state during the monopolar review 1-month post-implantation. Results: We analyzed 137 monopolar stimulation observations (105 GPi, 32 STN). In the GPi cohort, discriminative fiber tract analysis showed a strong association between SID and the modulation of subthalamo-pallidal fibers. This correlation was confirmed using leave-one-out and five-fold cross-validation. We further validated this model by predicting SID in independent STN and GPi cohorts, with the GPi-based model accounting for significant variance in SID occurrence in both cohorts. Conclusions: SID from STN or GPi DBS likely shares a common pathway via subthalamo-pallidal connectivity. DBS modulation of these fibers correlates with SID, as confirmed by multiple cross-validation methods. These findings suggest that the fibers are part of a more extensive and yet-to-be-fully-characterized dyskinesia network. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.