Objective: To assess the effect of 7-session transcranial temporal interference stimulation(tTIS) targeting dentate nucleus (DN) in people with essential tremor (ET).

Background: ET is a common neurological disorder characterized by rhythmic involuntary movements. Current pharmacological treatments offer limited efficacy and surgical interventions such as deep brain stimulation (DBS) are often required, while their invasive nature deters adoption. Emerging evidence has highlighted DN as a promising therapeutic target, given as the major output node of aberrant cerebellar activity within tremor-related networks. However, direct DBS targeting DN is anatomically challenging. tTIS represents an innovative non-invasive approach to modulate deep brain structures, providing the potential to target deep cerebellar nuclei and modulate pathological tremor circuits without surgery.

Method: In this open-label, non-randomized, single-arm trial, participants underwent 7 sessions of DN-tTIS, each lasting 20 minutes. Stimulation was delivered using a 2000 Hz carrier frequency and a 130 Hz interfering frequency, with the electrode position and related current optimized to generate an on-target electric field of 0.67 V/m. The primary endpoint was the change in Fahn-Tolosa-Marín Tremor Rating Scale (FTM-TRS) score for the dominant tremor hand (ipsilateral to stimulation) from baseline to completion of the 7-session intervention. Secondary endpoints included changes in total FTM-TRS score and subscores. Exploratory functional MRI was performed in a subset of participants.

Results: After 7 sessions of DN-tTIS, ipsilateral FTM-TRS score showed a significant reduction, decreasing by 2.12 points from 13.71 ± 5.62 to 11.59 ± 4.47 (P < 0.001). Linear mixed-model analysis further supported a cumulative treatment effect across sessions (R² = 0.97, P = 0.002). Total FTM-TRS score was significantly reduced by 5.06 points (P < 0.001), with significant improvements observed in part A (P = 0.001) and B (P = 0.004), but not in part C (P = 0.059). Exploratory functional MRI demonstrated reduced intrinsic activity and functional connectivity within the cerebello-thalamo-cortical (CTC) network.

Conclusion: DN-tTIS may ameliorate essential tremor by desynchronizing CTC circuits, offering a potential targeted non-invasive therapeutic strategy. Further controlled clinical trials are needed to confirm its efficacy.

Figure 1

Figure 2

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/temporal-interference-stimulation-of-dentate-nucleus-suppressed-essential-tremor/