Abnormal structure-function relationship in spasmodic dysphonia

Abstract

Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure-function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level-dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD.

Figure 1.

Regions of abnormal GMV (A), CT (B), and brain activation during symptomatic syllable production (C) in SD patients compared with healthy subjects are presented on the inflated cortical surfaces; differences between the groups in the subcortical regions and cerebellum are shown on the series of axial and coronal brain images. The color bars represent F values (A), P value (B), and t-values (C) and reflect the significance of abnormalities of GMV, CT, and activation extent, respectively. LA, larynx area; TR, trunk area; PM, premotor cortex; STG, superior temporal gyrus; Put, putamen; PAG, periaqueductal gray; M1, primary motor cortex; S1, primary somatosensory cortex; aIns, anterior insula; IPL, inferior parietal lobule.

Figure 2.

Relationships of brain activation during symptomatic syllable production with the GMV (A) and CT (D) in SD patients are shown on inflated cortical surfaces; correlations in the cerebellum are shown on the coronal images. The color bar represents r values. The plots depict correlations between the GMV (in liter) and BOLD percent signal change (B, C) and between CT (in cm) and BOLD percent signal change (E, F) in the representative regions. STG, superior temporal gyrus; LA, larynx area of the sensorimotor cortex.

Figure 3.

Relationships of SD severity with the GMV (in liter) (A) and BOLD percent signal change during symptomatic syllable production (C) are shown on the inflated cortical surfaces; correlation in the cerebellum is shown on an axial image. The color bar represents t-values (A) and r values (C). (B, D) The plots depict representative correlations of (A) and (B). OP, parietal operculum; LA, larynx area; aIns, anterior insula; Cbl, cerebellum.

Figure 4.

Relationships of CT (in mm) with SD symptoms (A) and duration (D). (B, D) The plots show representative correlations between SD clinical characteristics and CT. aIns, anterior insula; STG, superior temporal gyrus. The color bar represents P values.