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Abstract
SummaryTremor can dominate Parkinson’s disease and yet responds less well to dopaminergic medications than do other cardinal symptoms of this condition [1, 2]. Deep brain stimulation can provide striking tremor relief, but the introduction of stimulating electrodes deep in the substance of the brain carries significant risks, including those of hemorrhage [3]. Here, we pioneer an alternative approach in which we noninvasively apply transcranial alternating current stimulation (TACS) over the motor cortex [4, 5] to induce phase cancellation of the rest tremor rhythm. We first identify the timing of cortical oscillations responsible for rest tremor in the periphery by delivering tremor-frequency stimulation over motor cortex but do not couple this stimulation to the on-going tremor—instead, the rhythms simply “drift” in and out of phase alignment with one another. Slow alternating periods of phase cancellation and reinforcement result, informing on the phase alignments that induce the greatest change in tremor amplitude. Next, we deliver stimulation at these specified phase alignments to demonstrate controlled suppression of the on-going tremor. With this technique we can achieve almost 50% average reduction in resting tremor amplitude and in so doing form the basis of a closed-loop tremor-suppression therapy that could be extended to other oscillopathies.
Highlights
Tremor amplitude is clearly dependent on the phase alignment between transcranial alternating current stimulation (TACS) and tremor signals (Figure 1A)
Tremor amplitudes in this case are demonstrably lower in quadrant IV (6.2% decrease; see Figure 1B) and higher when tremor leads TACS in quadrant I (8.2% increase)
Tremor amplitude can be assessed in relation to all combinations of stimulation and tremor phase (Figure 1C)
Summary
Experiment 1: Phase Drift Drift results from a single patient displaying tremor-dominant Parkinson’s disease are presented in Figure 1 (see Supplemental Experimental Procedures available online). Tremor amplitude is clearly dependent on the phase alignment between TACS and tremor signals (Figure 1A). Tremor amplitude can be assessed in relation to all combinations of stimulation and tremor phase (Figure 1C).
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