Freek Nieuwhof1, Ivan Toni1, Arthur W G Buijink2, Anne-Fleur van Rootselaar2, Bart P C van de Warrenburg3, Rick C Helmich4. 1. Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. 2. Department of Neurology and Clinical Neurophysiology, Amsterdam University Medical Centers, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands. 3. Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands. 4. Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands; Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands. Electronic address: Rick.Helmich@radboudumc.nl.
Abstract
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.
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.