Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia

Abstract

Tremor, affecting a dystonic body part, is a frequent feature of adult-onset dystonia. However, our understanding of dystonic tremor pathophysiology remains ambiguous as its interplay with the main co-occurring disorder, dystonia, is largely unknown. We used a combination of functional MRI, voxel-based morphometry and diffusion-weighted imaging to investigate similar and distinct patterns of brain functional and structural alterations in patients with dystonic tremor of voice (DTv) and isolated spasmodic dysphonia (SD). We found that, compared to controls, SD patients with and without DTv showed similarly increased activation in the sensorimotor cortex, inferior frontal (IFG) and superior temporal gyri, putamen and ventral thalamus, as well as deficient activation in the inferior parietal cortex and middle frontal gyrus (MFG). Common structural alterations were observed in the IFG and putamen, which were further coupled with functional abnormalities in both patient groups. Abnormal activation in left putamen was correlated with SD onset; SD/DTv onset was associated with right putaminal volumetric changes. DTv severity established a significant relationship with abnormal volume of the left IFG. Direct patient group comparisons showed that SD/DTv patients had additional abnormalities in MFG and cerebellar function and white matter integrity in the posterior limb of the internal capsule. Our findings suggest that dystonia and dystonic tremor, at least in the case of SD and SD/DTv, are heterogeneous disorders at different ends of the same pathophysiological spectrum, with each disorder carrying a characteristic neural signature, which may potentially help development of differential markers for these two conditions.

Keywords: Dystonic tremor; Laryngeal dystonia; Tbss; VBM; fMRI.

Figure 1

A) Common functional and structural brain differences in SD and SD/DTv patients compared to healthy controls. Regions of abnormal functional activation during symptomatic speech production (I), gray matter volume (II) and white matter integrity (III) in SD and SD/DTv patients compared with controls are shown on a series of axial and sagittal slices in an AFNI standard Talairach-Tournoux space. (B) Distinct alterations in brain function (I) and white matter integrity (II) between SD and SD/DTv patients are shown on a series of axial slices in the standard space. The color bars represent the t-score. PT – patients; HV – healthy volunteers; SD – spasmodic dysphonia; SD/DTV – spasmodic dysphonia with dystonic tremor of voice.

Figure 2

Correlations between abnormal function, structure and clinical characteristics of SD (A) and SD/DTv (B). Panels I-A and II-A depict the overlap between significant clusters of functional and gray matter volumetric abnormalities identified in the comparison of SD and SD/DTv with healthy controls on a series of axial slices in an AFNI standard Talairach-Tournoux space. Panels II-B-C and II-B-D show correlations disorder onset and severity with the significant clusters of overlap.

Figure 3

A schematic diagram summarizing the main findings of functional and structural abnormalities in patients with SD and SD/DTv. The middle panel shows the alterations of brain function and structure that are common between the two disorders; the right and left panels show abnormalities that are characteristic to dystonia and dystonic tremor, respectively. The arrow signifies the presence of shared abnormalities by SD and SD/DTv as well as the presence of disorder-specific alterations. L – left; R – right; F – functional abnormality; G – abnormal gray matter volume; W – abnormal white matter integration.