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. 2025 Jun;40(6):1195-1199.
doi: 10.1002/mds.30185. Epub 2025 Apr 2.

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

Hannah Schoenwald  1 , Bahne H Bahners  1   2 , Silja Kannenberg  1 , Till A Dembek  3 , Michael T Barbe  3 , Dafina Sylaj  1   2 , Anja Spiewok  2 , Saskia Elben  1   2 , Tomke Muettel  4 , Jan Vesper  5 , Philipp Slotty  6 , Alfons Schnitzler  1   2 , Stefan J Groiss  1   2   7
Affiliations

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

Hannah Schoenwald et al. Mov Disord. 2025 Jun.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: deep brain stimulation; left hemisphere; low‐frequency stimulation; neurocognitive side effects; verbal fluency sweet spot.

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Figures

FIG. 1
FIG. 1
Verbal fluency mean z‐scores (Regensburger Wortflüssigkeitstest, RWT) across stimulation conditions. Asterisks represent the post‐hoc test results after multiple comparison correction using Tukey's method between conditions (*P < 0.05, **P < 0.01, ***P < 0.001). Left column shows exemplary contact orientations. dDBS, directional deep brain stimulation. [Color figure can be viewed at wileyonlinelibrary.com]
FIG. 2
FIG. 2
Probabilistic stimulation mapping of the z‐scored verbal fluency (VF) improvement in three‐ and two‐dimensional views. VF improvement is shown in the weighted mean‐effect image (outliers excluded) and scaled according to standardized regression coefficient (see color bar on right). The cluster of voxels with significant above‐average improvement is highlighted, with non‐significant voxels in transparent colors. The subthalamic nucleus (STN) according to the DISTAL atlas is outlined in grey. L, left; R, right; A, anterior; P, posterior. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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