Objective: To investigate whether transcranial temporal interference stimulation (tTIS) targeting different deep brain regions produces symptom-specific improvements consistent with established deep brain stimulation (DBS) outcomes in Parkinson’s disease (PD).

Background: Transcranial temporal interference stimulation is an emerging non-invasive therapy for PD that may modulate deep brain structures. However, its ability to selectively target subcortical regions remains uncertain due to the complexity of electric field propagation through neural tissue. This study examines whether targeting the subthalamic nucleus (STN) versus the internal globus pallidus (GPi) with tTIS produces symptom-specific effects consistent with DBS outcomes for these respective targets.

Method: This pilot study included six PD patients (age 66.3 ± 7.7 years, 2 females, H&Y stage 1–2.5) in a randomized, crossover, double-blind design. Participants in the medication-ON state received STN-tTIS or GPi-tTIS (130 Hz) in a randomized order with a one-week washout period between sessions. Motor symptoms were assessed before and immediately after the 20-minute tTIS session using MDS-UPDRS-III. A paired t-test compared the effects of STN-tTIS and GPi-tTIS on motor symptom alleviation. The significance level (α) was set at 0.05.

Results: STN-tTIS (from 21.2 ± 9.2 to 11.5 ± 6.1) demonstrated superior efficacy compared to GPi-tTIS (from 19.5 ± 5.3 to 12.7 ± 4.5) in reducing the total UPDRS-III score (tTIS-induced reduction: 48.6% vs. 35.5%, p = 0.016). Compared to GPi-tTIS, STN-tTIS showed a trend toward greater reduction in bradykinesia scores (STN-tTIS-induced bradykinesia alleviation: 65.8% vs. GPi-tTIS-induced bradykinesia alleviation: 48.0%, p = 0.077). In contrast, no significant difference was observed in the alleviation of tremor (STN-tTIS: 58.3% vs. GPi-tTIS: 50.5%, p = 0.514), rigidity (STN-tTIS: 38.9% vs. GPi-tTIS: 26.6%, p = 0.603), or axial symptoms (STN-tTIS: 25.0% vs. GPi-tTIS: 45.0%, p = 0.534).

Conclusion: This pilot study reveals symptom-specific effects that correspond remarkably with established DBS outcomes. STN-tTIS provides superior overall efficacy compared to GPi-tTIS, particularly for bradykinesia relief. Meanwhile, both targets provide comparable benefits for tremor and rigidity. Despite doubts about precision, tTIS may achieve target-specific effects akin to DBS, warranting further study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subthalamic-versus-pallidal-temporal-interference-stimulation-in-parkinsons-disease-a-pilot-study/