Essential tremor amplitude modulation by median nerve stimulation

Carolina Reis,Alek Pogosyan,Beatriz S Arruda,Peter Brown,Hayriye Cagnan

doi:10.1038/s41598-021-96660-6

Carolina Reis, Alek Pogosyan + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-96660-6

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Abstract

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. Patients are usually treated using medications which have limited effects on tremor and may cause side-effects. Surgical therapies are effective in reducing essential tremor, however, the invasive nature of these therapies together with the high cost, greatly limit the number of patients benefiting from them. Non-invasive therapies have gained increasing traction to meet this clinical need. Here, we test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Peripheral stimulation induced a subtle but significant modulation in five out of nine patients—this modulation consisted mainly of amplification rather than suppression of tremor amplitude. Modulatory effects of stimulation were more pronounced when patient’s tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects. This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation.

Highlights

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb
While we have found a main effect of stimulation phase on tremor severity at the group level (Friedman’s test applied to amplitude response curves (ARCs)’s realigned to the phase-affording maximum tremor amplification, P = 0.0025, dF = 11, and to ARC’s realigned to the phase-affording maximum tremor suppression P = 0.0072, dF = 11, compared to no change or zero); changes on tremor severity induced by stimulation were not statistically different from those spontaneously achieved during no stimulation after aligning individual surrogate ARCs to spontaneously observed tremor amplification and suppression (p = 0.702, tremor amplification and p = 0.129, tremor suppression) (Fig. 2)
Contrasting the information contained in the individual ARCs after median split according to amplitude, we found that the magnitude of stimulation effects, quantified as mean of absolute ARCs during low and high tremor amplitude, differed

Summary

Introduction

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. We test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Modulatory effects of stimulation were more pronounced when patient’s tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation. We explore the second approach and aim to activate Group I muscle spindle afferents using median nerve stimulation phase-locked to patient’s tremor

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