The extrinsic risk and its association with neural alterations in spasmodic dysphonia

Abstract

Introduction: Spasmodic dysphonia (SD) is an isolated focal dystonia characterized by laryngeal spasms during voluntary voice production. Environmental factors have been assumed to play a role in SD pathophysiology; however, the exact extrinsic risk factors and their association with neural alterations remain unknown.

Methods: A total of 186 SD patients and 85 healthy controls completed a structured 177-question survey, consisting of questions on general biographical information, medical history, symptomatology of dystonia. Data were imputed in a stepwise regression model to identify extrinsic risk factors for SD. In addition, functional MRI data from a subset of this cohort were analyzed to determine brain activation abnormalities associated with the SD extrinsic risk.

Results: We found that (1) recurrent upper respiratory infections, gastroesophageal reflux, and neck trauma, all of which influence sensory feedback from the larynx, represent extrinsic risk factors, likely triggering the manifestation of SD symptoms, and (2) neural alterations in the regions necessary for sensorimotor preparation and integration are influenced by an extrinsic risk in susceptible individuals.

Conclusions: These findings provide evidence for the extrinsic risk in SD development and demonstrate the link with alterations in the sensorimotor preparatory network that collectively contribute to the multifactorial pathophysiology of SD.

Trial registration: ClinicalTrials.gov NCT03042975.

Keywords: Case-control study; Extrinsic risk; Laryngeal dystonia; fMRI.

Conflict of interest statement

Relevant conflicts of interest/financial disclosures: None

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

Figure 1.

Statistically significant differences in brain activity during symptomatic speech production in (A) SD patients with extrinsic risk factors compared to healthy controls (HC) and (B) SD patients without risk factors compared to healthy controls. Axial and sagittal brain slices are shown in the AFNI standard Talairach-Tournoux space. Color bar represents the t-score at a corrected p ≤ 0.05. PreMC – premotor cortex; M1 – primary motor cortex; IPC – inferior parietal cortex; A1 – primary auditory cortex.

Figure 2.

A map of significant differences in brain activity during symptomatic speech production in (A) familial SD patients compared to healthy controls, and (B) sporadic SD patients compared to healthy controls stratified by the presence of the extrinsic risk. Axial and sagittal brain slices are shown in the AFNI standard Talairach-Tournoux space. PreMC – premotor cortex; M1 – primary motor cortex; IPC – inferior parietal cortex; SFG – superior frontal gyrus.

Figure 3.

Schematic representation of distinct regional brain alterations dependent on the influence of extrinsic risk factors in spasmodic dysphonia. PreMC - premotor cortex; M1 -primary motor cortex; A1 - primary somatosensory cortex; IPC - inferior parietal cortex.