Theta-Gamma Subthalamic Stimulation for Verbal Fluency in Parkinson's Disease: A Randomized, Crossover Trial

Background: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves Parkinson's disease (PD) motor symptoms but may deteriorate verbal fluency (VF). Theta stimulation showed potential cognitive benefits associated with motor worsening. Objectives: This randomized, double-blind, crossover study evaluated the efficacy and safety of combined theta-gamma frequency stimulation on VF in PD patients with STN-DBS. Methods: Patients were randomized 1:1 for standard or theta-gamma stimulation. VF, motor, and non-motor symptoms were assessed at baseline, 1 h, and 1 month after each period. Data were analyzed using a linear mixed-effects model. Results: Twelve patients completed the study. Non-episodic (P = 0.038) and episodic VF (P = 0.030) improved after 1 month of theta-gamma stimulation, while phonemic and switching fluency were unchanged. Motor and non-motor outcomes were unaffected by the stimulation, with mild adverse events. Conclusion: Combined theta-gamma stimulation may enhance VF in PD patients with STN-DBS without worsening motor symptoms or safety concerns. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.