Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation

Mo Chen, Rebekah L S Summers, Cecília N Prudente, George S Goding, Sharyl Samargia-Grivette, Christy L Ludlow, Teresa J Kimberley, Mo Chen, Rebekah L S Summers, Cecília N Prudente, George S Goding, Sharyl Samargia-Grivette, Christy L Ludlow, Teresa J Kimberley

Abstract

Background: Reduced intracortical inhibition is a neurophysiologic finding in focal dystonia that suggests a broader problem of impaired cortical excitability within the brain. A robust understanding of the neurophysiology in dystonia is essential to elucidate the pathophysiology of the disorder and develop new treatments. The cortical silent period (cSP) is a reliable, non-invasive method to measure intracortical inhibition in the primary motor cortex associated with a muscle of interest. In adductor spasmodic dysphonia (AdSD), cSP of the laryngeal motor cortex (LMC) which directly corresponds to the affected musculature, the thyroarytenoid (TA), has not been examined.

Objective: This work evaluated the cSP of the LMC and the relationship between cSP and functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) activation in people with AdSD (n = 12) compared to healthy controls (CTL, n = 14).

Results: Shortened LMC cSP were observed bilaterally in people with AdSD vs CTL (F(1, 99) = 19.5226, p < 0.0001), with a large effect size (η2 = 0.1834). Between-group fMRI analysis revealed greater activation in bilateral LMC in the AdSD > CTL contrast as compared to CTL > AdSD contrast. Correlation analysis showed that people with AdSD have positive correlation of left LMC BOLD activation and the cSP. Further, the right LMC cSP lacks either positive or negative associations with BOLD activation. CTL individuals displayed both positive and negative correlations between cSP and BOLD activation in the left LMC. In CTL, the LMC cSP and BOLD activation showed exclusively negative correlations in both hemispheres.

Conclusion: In AdSD, the cortical activation during phonation may not be efficiently or effectively associated with inhibitory processes, leading to muscular dysfunction. These findings may give insight into the maladaptive cortical control during phonation in people with AdSD.

Keywords: Adductor spasmodic dysphonia; Cortical silent period; Laryngeal motor cortex; Thyroarytenoid, laryngeal dystonia; Transcranial magnetic stimulation.

Conflict of interest statement

Declaration of competing interest Authors have no conflict of interest to declare.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1.
Fig. 1.
Representative example of TMS evoked responses from one adductor spasmodic dysphonia (AdSD) and one healthy control (CTL) participant. Left: Waterfall plot of all responses from one thyroarytenoid muscle (left TA) evoked from single pulse TMS delivered over the right laryngeal motor cortex. Time 0 represents the TMS artifact. Observable is the resultant motor evoked potential (MEP) and cortical silent period (cSP). Right: The corresponding averaged trace illustrating the cSP values of 53.4 ms from the CTL participant and 42.7 ms from the AdSD participant. TMS: transcranial magnetic stimulation.
Fig. 2.
Fig. 2.
Mean cortical silent period (±SD) in AdSD vs CTL. Shortened cSP in laryngeal motor cortex (LMC) was observed in AdSD as compared to CTL. *: pη2 = 0.1834. (TA = thyroarytenoid muscle)
Fig. 3.
Fig. 3.
Between group comparisons of fMRI BOLD activation in M1 during phonation. Dashed lines (projection of a circle with a radius of 5mm): estimated LMC area projection on inflated brain surface. Warm colors represent AdSD>CTL, cool colors represent CTL>AdSD. Results indicate greater activation in AdSD vs CTL in LMC area, particularly in the left hemisphere.
Fig. 4.
Fig. 4.
Laryngeal motor cortex (LMC) cortical silent period (cSP) and BOLD activation correlation. In AdSD (top), the cSP were primarily positively correlated with BOLD with significant correlations exclusively in the left LMC. There were negative correlations in the more superior M1 regions not associated with the larynx. In the control group (CTL) (bottom), the cSP displayed both positive and negative correlations with BOLD. There was primarily positive correlations that were stronger in the left vs right. Negative correlations were few and in the left LMC only. Dashed lines (projection of a circle with a radius of 5mm): estimated LMC area projection on inflated brain surface.

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