Antero-Lateral Subthalamic Nucleus Theta Stimulation Improves Verbal Fluency in Parkinson's Disease

Low-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with positive effects on verbal fluency (VF) in patients with Parkinson's disease. This prospective study investigates stimulation direction-dependent and site-specific effects of theta frequency DBS on VF.

In a double-blind, cross-over design (n = 20), we tested VF during left subthalamic theta stimulation (stimulation-off, omnidirectional, and threedirectional stimulation conditions). DBS electrode localization and electric field calculations were performed (n = 18). Probabilistic sweet spot mapping identified voxels with significant change in VF.

Best directional stimulation improved VF performance significantly compared with the stimulation-off and omnidirectional stimulation condition. This effect followed a medial-to-anterolateral gradient with higher VF improvement observed on the border between the motor and associative subparts of the STN.

We provide first proof-of-principle evidence that directional theta frequency DBS improves VF, possibly related to stimulation of the anterolateral STN. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.