Abstract
EBioMedicine. 2026 Apr 2;127:106245. doi: 10.1016/j.ebiom.2026.106245. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
METHODS: 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.
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: National Natural Science Foundation of China (NSFC11932013).
PMID:41932202 | DOI:10.1016/j.ebiom.2026.106245
UK DRI Authors
