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

OBJECTIVE

To establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked transcranial alternating current stimulation (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 30 s 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.

SIGNIFICANCE: We show tremor phenotype dependent involvement of the cerebellum in dystonic tremor syndrome. Tremor phenotype may thus guide optimal intervention targets.