Tremor modulation: a systematic review of resetting by single-pulse transcranial magnetic stimulation.

Abstract

Background/aim: Tremor arises from mechanical, reflex, or central oscillatory mechanisms. Transcranial magnetic stimulation (TMS) can transiently perturb ongoing tremor and enables the quantitative assessment of phase resetting, offering circuit-level insight into tremor types. Although numerous studies have applied TMS-induced resetting, the findings have not been systematically reviewed. This study systematically reviews human studies evaluating TMS-induced tremor resetting across tremor types.

Materials and methods: A systematic search of PubMed and Google Scholar identified human studies using TMS to perturb tremor or rhythmic movement. Search terms included "tremor resetting," "resetting of tremor," "tremor phase shift," "tremor phase reset," "transcranial magnetic stimulation," and "central oscillator." Inclusion criteria were human participants, experimental TMS perturbation, and quantitative tremor phase/resetting outcomes. Exclusion criteria were animal studies, therapeutic repetitive TMS trials without resetting analyses, and isolated case reports. Two researchers independently screened and extracted data. The PRISMA 2020 guidelines were followed.

Results: Twenty-one studies were identified, three of which were excluded from the primary synthesis (two case reports and one qualitative-only design). Eighteen studies remained, which addressed essential tremor (ET) (n = 6), Parkinson's disease tremor (PDT) (n = 7), orthostatic tremor (OT) (n = 4), palatal tremor (n = 1), dystonic tremor (DT) (n = 1), and voluntary rhythmic movement (n = 4). M1 stimulation reset ET, postural PDT, OT, palatal tremor, DT, and voluntary rhythmic movements. Rest PDT had inconsistent resetting by M1 stimulation and no resetting by cerebellar stimulation. Cerebellar stimulation reset postural PDT but not ET. The resetting index was associated with the stimulus intensity and duration of the silent period.

Conclusion: TMS-induced resetting is a strong physiological tool for differentiating tremor circuits. M1 acts as a major convergence node, while cerebellar involvement is tremor-specific. Methodological heterogeneity and small samples limit the comparability of study results. Advances in targeting technologies and closed-loop and phase-locked protocols could enhance the diagnostic and therapeutic utility of resetting paradigms.