Objective: To test whether hand tremor can be mitigated by delivering an electrical stimulation to the ipsilateral cerebellum, phase-locked to the tremulous hand movement.

Background: Essential Tremor (ET) is believed to originate from oscillatory neuronal network activity involving cortex, thalamus and cerebellum. tACS has been devised as a safe and non-invasive means to deliver weak, exogenous and periodic electric fields through cutaneous electrodes to the human brain in order to modulate oscillatory network activity.

Methods: We tested this stimulation modality on postural tremor in ET patients (n=11) in a quadruple replication, semi-randomized block-design including six phase-locked, one non phase-locked stimulation and one sham condition. Each block of stimulation included 15s of baseline period, 30s of stimulation period and 15s of post stimulation period. Tremor activity measured by a tri-axial accelerometer was used to compute the instantaneous tremor phase in real-time using a Hilbert transformation-based algorithm implemented on a microcontroller (Arduino Due). A sinusoidal voltage waveform was generated a) with a frequency equalling the tremor frequency adjusted to have a fixed lag of 0°, 60°, 120°, 180°, 240° or 300° relative to the instantaneous tremor phase (phase-locked condition), b) at the tremor frequency without adjustment (non phase-locked condition), c) and dropped to zero after the initial 5 s ramp-up period (sham condition). The stimulation signal was fed to an isolated current source DS4 (Digitimer Ltd., Welwyn Garden City, UK). Stimulation was delivered just above the individual cutaneous sensory threshold via an active (30x30mm) and return (50x50mm) skin electrode placed over the lateral cerebellar hemisphere and contralateral, frontal cortex. After removal of sessions with baseline tremor amplitude ± 2 SD of mean baseline recordings per subject, offline analysis was done using MatLab (The MathWorks). Changes in tremor amplitude were calculated as z-scores ± SD.

Results: Phase-locked stimulation was achieved reliably throughout the phase-spectrum. A comparison of tremor amplitude across all blocks showed a significant reduction in tremor amplitude during phase-locked (-2.22 ± 1.5) versus non phase-locked stimulation (-0.94 ± 0.92; p=0.01; paired t-test).

Conclusions: Our data provide first evidence that phase-locked tACS can modulate ET tremor amplitude, most likely by influencing network activity via cerebellar cortical stimulation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phase-locked-transcranial-alternating-current-stimulation-of-the-cerebellum-for-essential-tremor/