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.

Phenotype‐ and genotype‐specific structural alterations in spasmodic dysphonia

“…In one of the first studies, Simonyan and colleagues showed abnormal integrity of white matter in the genu of the internal capsule, lentiform nucleus, thalamus, and cerebellum . Follow‐up studies have extended these findings by identifying further alterations in white matter underlying inferior frontal gyrus and associative pathways that are also shared with other task‐specific dystonias and dystonic voice tremor . Gray matter abnormalities in SD patients compared with healthy controls have been reported to involve bilateral primary sensorimotor and premotor cortex, superior/middle temporal, supramarginal, inferior frontal gyri, inferior parietal lobule, insula, putamen, thalamus, and cerebellum .…”

“…Typically, SD has a sporadic onset, with only up to 16% of patients reporting a familial history of dystonia . Several structural abnormalities underlying the speech sensorimotor network have been described as potential contributors to disorder pathophysiology in SD patients compared with healthy subjects . In one of the first studies, Simonyan and colleagues showed abnormal integrity of white matter in the genu of the internal capsule, lentiform nucleus, thalamus, and cerebellum .…”

Defining differences in patient characteristics between spasmodic dysphonia and laryngeal tremor

“…Our findings are similar to those from case series, which found females make up 83% to 93% and 62% to 79% of patients with vocal tremor and ADSD, respectively. However, results herein also show a significantly greater proportion of women among those with ADSD + LT than among those presenting with ADSD …”

“…Animal models have also found that cerebellar interactions with other neural circuits contribute to dystonia, but the nature of this interaction has not been elucidated . Interestingly, neural abnormalities in ADSD and those with ADSD with LT have been shown to involve similar regions in sensorimotor processing and execution of motor commands . However, patients with concomitant tremor have additional cerebellar changes, suggesting possible overlap with isolated LT of the voice.…”

Spasmodic dysphonia and voice tremor: an analysis of the neuropathophysiology, clinical features and treatment options

“…to not only what was reported in the neuropathophysiology component of this thesis, but also to pre -existing literature on the neuropathophysiologic alterations seen in SD, with increased brain activity seen bilaterally in sensorimotor cortical regions, basal ganglia and cerebellum. (13,104) The first post -treatment scan demonstrated the converse, with decreased brain activity in the primary sensorimotor cortex, putamen and cerebellum. On the second post -treatment scan these changes still remained in the putamen and cerebellum but the activity in the primary sensorimotor cortex had normalized.…”