Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome

Barbara Morera Maiquez, Hilmar P Sigurdsson, Katherine Dyke, Eleri Clarke, Polly McGrath, Matthew Pasche, Anupriya Rajendran, Georgina M Jackson, Stephen R Jackson, Barbara Morera Maiquez, Hilmar P Sigurdsson, Katherine Dyke, Eleri Clarke, Polly McGrath, Matthew Pasche, Anupriya Rajendran, Georgina M Jackson, Stephen R Jackson

Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the occurrence of vocal and motor tics. Tics are involuntary, repetitive movements and vocalizations that occur in bouts, typically many times in a single day, and are often preceded by a strong urge-to-tic-referred to as a premonitory urge (PU). TS is associated with the following: dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits implicated in the selection of movements, impaired operation of GABA signaling within the striatum, and hyper-excitability of cortical sensorimotor regions that might contribute to the occurrence of tics. Non-invasive brain stimulation delivered to cortical motor areas can modulate cortical motor excitability, entrain brain oscillations, and reduce tics in TS. However, these techniques are not optimal for treatment outside of the clinic. We investigated whether rhythmic pulses of median nerve stimulation (MNS) could entrain brain oscillations linked to the suppression of movement and influence the initiation of tics in TS. We demonstrate that pulse trains of rhythmic MNS, delivered at 12 Hz, entrain sensorimotor mu-band oscillations, whereas pulse trains of arrhythmic MNS do not. Furthermore, we demonstrate that although rhythmic mu stimulation has statistically significant but small effects on the initiation of volitional movements and no discernable effect on performance of an attentionally demanding cognitive task, it nonetheless leads to a large reduction in tic frequency and tic intensity in individuals with TS. This approach has considerable potential, in our view, to be developed into a therapeutic device suitable for use outside of the clinic to suppress tics and PU in TS.

Keywords: EEG; Tourette syndrome; median nerve stimulation; mu entrainment; tic suppression.

Conflict of interest statement

Declaration of interest The authors declare no competing interests.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Study Design and Time-Frequency Plots of ERSP for Rhythmic and Arrhythmic MNS (A) Illustration of rhythmic 12 Hz and arrhythmic bursts of MNS. (B) Time-frequency plots of ERSP for arrhythmic (top) and rhythmic (middle) MNS and the rhythmic minus arrhythmic subtraction (bottom). The time course of the 12 Hz ERSP, measured over the left sensorimotor region (C1) and corresponding to the initial 3 MNS pulses, are contained within W1. The time course of the 12 Hz ERSP for the remaining MNS pulses (4–10) are contained within W2. (C) Results of statistical comparison of ERSP values for arrhythmic and rhythmic 12 Hz measured at C1. Statistically significant values are indicated with ∗ symbols (p < 0.05 FDR-corrected). For further information please refer to Figure S2.
Figure 2
Figure 2
Time-Frequency Plots of Phase-Locking Values for Rhythmic and Arrhythmic MNS (A) Time-frequency plots of PLVs for arrhythmic (top) and rhythmic (middle) MNS and the rhythmic minus arrhythmic subtraction (bttom). The time course of the 12 Hz PLVs, measured over the left sensorimotor region (C1) and corresponding to the initial 3 MNS pulses, are contained within W1. The time course of the 12 Hz PLVs for the remaining MNS pulses (4–10) are contained within W2. (B) Time-frequency plots of PLVs for 12 Hz MNS measured over the contralateral sensorimotor (C1) (top) and ipsilateral sensorimotor (C2) and the C1 minus C2 subtraction (bottom). (C) Statistical comparison of PLVs for arrhythmic and rhythmic 12 Hz measured at over the contralateral sensorimotor cortex (C1). Statistically significant values are indicated with ∗ symbols (p < 0.05 FDR-corrected). (D) Statistical comparison of PLVs measured over the contralateral sensorimotor (C1) and ipsilateral sensorimotor (C2) for rhythmic 12 Hz MNS. Statistically significant values are indicated with ∗ symbols (p < 0.05 FDR-corrected).
Figure 3
Figure 3
Evoked Activity in Response to Each Successive Pulse of MNS Waveforms recorded from over the left sensorimotor region (C1) are shown for arrhythmic (cyan) and rhythmic (pink) MNS.
Figure 4
Figure 4
Effects of Rhythmic 12 Hz Versus Arrhythmic MNS on the Initiation of Choice-RTs Choice-RT data for correct trials for rhythmic 12Hz versus arrhythmic MNS. Shown the left are data for random presentation of rhythmic and arrhythmic MNS pulse trains, and on the right is a blocked presentation of rhythmic and arrhythmic MNS. The boxplot shows the median values (red line), inter-quartile ranges (blue box), and individual data points (x) in each case. Red “∗” symbols represent outliers. In both cases, the difference between means for rhythmic and arrhythmic MNS was statistically significant (p < 0.05).
Figure 5
Figure 5
Effects of Rhythmic 10 Hz MNS versus No Stimulation on Tic Frequency and Intensity, and the Urge-to-Tic, in Tourette syndrome Illustrates the effects of rhythmic 10 Hz MNS compared to a no-stimulation control condition. Shown on the top left are data for tic frequency as measured by the total number of tics recorded in each condition (p ∗ symbols represent individual data points that are statistical outliers. For further information please refer to Video S1: Representative Video 1, Related to Figure 5, Video S2: Representative Video 2, Related to Figure 5, Video S3: Representative Video 3, Related to Figure 5, Table S1, and Figure S2.

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