Phenotype- and genotype-specific structural alterations in spasmodic dysphonia

Abstract

Background: Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology.

Methods: Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes).

Results: Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus.

Conclusions: Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society.

Keywords: cortical thickness; diffusion-weighted imaging; genetics; laryngeal dystonia.

Conflict of interest statement

Relevant conflicts of interest/financial disclosures: none.

© 2017 International Parkinson and Movement Disorder Society.

Figures

FIG. 1

Group statistics of the comparison between ADSD and ABSD patients for cortical thickness (CT, panel I) and fractional anisotropy (FA, panel II). Regions of altered CT are superimposed on the inflated cortical surface of the MNI_305 template and thresholded at Pcorr < 0.01 with a minimum surface area of 80 mm2. TBSS results are shown on a series of sagittal slices of the subjects’ average FA maps transformed in the MNI standard brain. Maps were thresholded at Pcorr < 0.01 with a minimum cluster size of 50 voxels. The color bar represents t scores of group statistical comparisons. (A) Differences between homogeneous groups of ABSD and ADSD patients. (B) Differences between heterogeneous groups of ABSD and ADSD patients.

FIG. 2

Group statistics of the comparison between sporadic and familial SD patients for cortical thickness (CT, panel I) and fractional anisotropy (FA, panel II). Regions of altered CT are superimposed on the inflated cortical surface of the MNI_305 template and thresholded at Pcorr < 0.01 with minimum surface area of 80 mm2. TBSS results are shown on a series of sagittal and axial slices of the subjects’ average FA maps transformed in the MNI standard brain. Maps were thresholded at Pcorr < 0.01 with a minimum cluster size of 50 voxels. The color bar represents t scores of group statistical comparisons. (A) Differences between homogeneous groups of sporadic and familial SD patients. (B) Differences between heterogeneous groups of sporadic and familial SD patients.

FIG. 3

(A) Correlation between CT and mean number of voice breaks in the STG. (B) Diagram visually summarizing core genotypic and phenotypic alterations in CT and FA measures. CT, cortical thickness; FA, fractional anisotropy; STG, superior temporal gyrus; SCR, superior corona radiata; CC, corpus callosum; SMA, supplementary motor area; SLF, superior longitudinal fasciculus; MTG, middle temporal gyrus.