Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study

Cecília N Prudente, Mo Chen, Kaila L Stipancic, Katherine L Marks, Sharyl Samargia-Grivette, George S Goding, Jordan R Green, Teresa J Kimberley, Cecília N Prudente, Mo Chen, Kaila L Stipancic, Katherine L Marks, Sharyl Samargia-Grivette, George S Goding, Jordan R Green, Teresa J Kimberley

Abstract

Purpose: The effects of neuromodulation are virtually unexplored in adductor laryngeal dystonia (AdLD), a disorder characterized by involuntary contraction of intrinsic laryngeal muscles. Recent findings indicated that intracortical inhibition is reduced in people with AdLD. Low-frequency repetitive transcranial magnetic stimulation (rTMS) induces prolonged intracortical inhibition, but the effects in AdLD are unexplored. This pilot and feasibility study aimed to examine the safety, feasibility, and effects of a single session 1 Hz rTMS over the laryngeal motor cortex (LMC) in people with AdLD and healthy individuals.

Methods: The stimulation location was individualized and determined through TMS-evoked responses in the thyroarytenoid muscles using fine-wire electrodes. 1200 pulses of 1 Hz rTMS were delivered to the left LMC in two groups: Control (n = 6) and AdLD (n = 7). Tolerance, adverse effects, intracortical inhibition, and voice recordings were collected immediately before and after rTMS. Voice quality was assessed with acoustic-based and auditory-perceptual measures.

Results: All participants tolerated the procedures, with no unexpected adverse events or worsening of symptoms. No significant effects on intracortical inhibition were observed. In the AdLD group, there was a large-effect size after rTMS in vocal perturbation measures and a small-effect size in decreased phonatory breaks.

Conclusions: One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in AdLD. These preliminary findings support further investigation to assess clinical benefits in a future randomized sham-controlled trial. CLINICALTRIALS.GOV: NCT02957942, registered on November 8, 2016.

Keywords: Acoustics; Adductor laryngeal dystonia; Cortical silent period; Repetitive transcranial magnetic stimulation; Spasmodic dysphonia.

Conflict of interest statement

All authors declare no conflicts or competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Representative raw EMG data of two participants demonstrating the cortical silent period (cSP) waterfall plot collected before (Pre) and after (Post) a single session of 1 Hz rTMS delivered to the laryngeal motor cortex. Each plot shows all 30 trials from one participant for each group before and after rTMS. AdLD adductor laryngeal dystonia, EMG electromyography, MEP motor-evoked potential
Fig. 2
Fig. 2
Average cortical silent period (cSP) duration for each group at pre- and post-test. There was no significant difference within or between groups. The values for left and right thyroarytenoid muscles were averaged, since there was no significant difference between sides (see text for details). AdLD adductor laryngeal dystonia; ms milliseconds
Fig. 3
Fig. 3
Objective measures of phonatory function for each group at pre- and post-test. A–C Jitter, shimmer, and harmonics-to-noise ratio during sustained phonation of the/ɑ/vowel. (D) CPPS results for the sentence “We eat eels everyday” of the Spasmodic Dysphonia Attribute Inventory. AdLD adductor laryngeal dystonia; CPPS smoothed cepstral peak prominence; dB decibels; HNR harmonics-to-noise ratio
Fig. 4
Fig. 4
Pre- and post-rTMS changes in clinician-based voice measures. A Total phonatory breaks during the ten sentences of the Spasmodic Dysphonia Attribute Inventory; B Overall severity ratings on the CAPE-V. The Control group averages are shown for each measure along with the data for individual AdLD participants. AdLD adductor laryngeal dystonia; CAPE-V Consensus auditory-perceptual evaluation of voice

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