Phase-locked transcranial electrical brain stimulation for tremor suppression in dystonic tremor syndromes

Background: Tremor is a common and burdensome symptom in patients with dystonia, which is clinically heterogeneous and often resistant to treatment. The pathophysiology is suggested to involve abnormal activity in the cerebellum and motor cortex, but the causal role of these brain regions remains to be established. Transcranial alternating current stimulaton (TACS) can suppress rhytmic cerebral activity in other tremor disorders when phase-locked to the ongoing arm tremor, but the effect on dystonic tremor syndromes is unknown. Objective/Hypothesis: We aimed to establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked TACS. Methods: We applied phase-locked TACS over the ipsilateral cerebellum (N=14) and contralateral motor cortex (N=17) in dystonic tremor syndrome patients, while patients assumed a tremor-evoking posture. We measured tremor power using accelerometery during 30s stimulation periods at 10 different phase-lags (36-degrees increments) between tremor and TACS for each target. Post-hoc, TACS-effects were related to a key clinical feature: the jerkiness (regularity) of tremor. Results: Cerebellar TACS modulated tremor amplitude in a phase-dependent manner, such that tremor amplitude was suppressed or enhanced at opposite sides of the phase-cycle. This effect was specific for patients with non-jerky (sinusoidal) tremor (n=10), but absent in patients with jerky (irregular) tremor (n=4). Phase-locked stimulation over the motor cortex did not modulate tremor amplitude. Conclusions: This study indicates that the cerebellum plays a causal role in the generation of (non-jerky) dystonic tremor syndrome. Our findings suggest pathophysiologic heterogeneity between patients with dystonic tremor syndrome, which mirrors clinical variability.