Transcranial Temporal Interference Stimulation of the Right Globus Pallidus in Parkinson's Disease

Abstract

Background: Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored.

Objective: This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD.

Methods: Twelve participants with mild PD completed this randomized, double-blind, and sham-controlled experiment. Each of them received either 20-minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) in the "medication-on" state to assess the motor symptoms. The blinding efficacy and side effects were also assessed.

Results: tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS-UPDRS-III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS.

Conclusion: This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger-scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; globus pallidus internus; motor symptoms; noninvasive deep brain stimulation; temporal interference stimulation.

FIG. 1

Visit procedure of the study. tTIS, transcranial temporal interference stimulation; UPDRS‐III, Movement Disorder Society‐revised Unified Parkinson's Disease Rating Scale, Part III. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 2

Concept map of electrode placement and electric field modeling with the GPi (globus pallidus internus) montage. The colors show the transcranial temporal interference exposure (electric field modulation magnitude). [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 3

Effects of transcranial temporal interference stimulation on motor symptoms. (A) Total score of MDS‐UPDRS‐III. (B) The score of bradykinesia. (C) The score of tremor. tTIS, transcranial temporal interference stimulation; MDS‐UPDRS‐III, Movement Disorder Society‐revised Unified Parkinson's Disease Rating Scale, Part III; *significant difference. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 4

Relation between improvement in motor symptoms and symptoms before tTIS. (A) Total score of MDS‐UPDRS‐III. (B) The score of bradykinesia. (C) The score of tremor. tTIS, transcranial temporal interference stimulation; MDS‐UPDRS‐III, Movement Disorder Society‐revised Unified Parkinson's Disease Rating Scale, Part III. [Color figure can be viewed at wileyonlinelibrary.com]