Transcranial temporal interference stimulation targeting the subthalamic region for motor symptoms in Parkinson's...

Neuromodulation targeting the subthalamic region has shown clinical benefit for alleviating motor symptoms in people with Parkinson's disease (PD). Transcranial temporal interference stimulation (TIs) offers a non-invasive approach warranting clinical evaluation. We aimed to examine the feasibility/safety and preliminary effects of single-session, individualised TIs targeting the subthalamic nucleus (STN)-region on motor symptoms in people with PD.

This randomised, double-blind, sham-controlled 2 × 2 within-participant crossover study was conducted in Shanghai, China (May 24-August 31, 2024; ChiCTR2400084797). Thirty people with early-to-mid-stage idiopathic PD (Hoehn and Yahr 1.5-3) were enrolled. In the medication-off state, participants received 20 min of 130 Hz TIs targeting the STN-region or active sham in randomised order; the montage was individualised using structural MRI. Feasibility/safety outcomes included compliance, adverse events, and blinding guesses. Motor symptoms were assessed at baseline and immediately, 30 min, and 60 min post-stimulation using MDS-UPDRS-III. Primary treatment effects outcomes were responder rate (≥5-point reduction) and MDS-UPDRS-III total score change; secondary outcomes included subscores.

No serious adverse events occurred. Any adverse event was reported by 21/30 (70.0%) after TIs and 21/27 (77.8%) after sham (risk difference [TIs-sham] -6.9%, 95% CI: -21.6 to 7.7; P = 0.352); perceived stimulation was similar across conditions. Responder rate was statistically significantly higher after TIs than sham (70% vs 15%; risk difference 56.3%, 95% CI: 38.3-74.4; P < 0.001). Compared with sham, TIs was associated with greater reductions in MDS-UPDRS-III total score (mean difference [TIs-sham] 4.18 immediately, 6.83 at 30 min, and 6.12 at 60 min; all 95% CIs excluded 0; P < 0.001), with statistically significant between-condition differences at all post-stimulation time points. Bradykinesia and tremor showed similar response patterns, whereas effects for rigidity and axial signs were not consistent.

In this pilot crossover study, a single session of TIs targeting the STN-region was feasible and well tolerated, and was associated with short-term improvements in motor symptoms compared with sham. Larger trials are warranted to confirm efficacy, durability, repeated-session dosing, and anatomical specificity, with continued emphasis on risk-benefit reporting.

National Natural Science Foundation of China (NSFC11932013).