Neural correlates of abnormal sensory discrimination in laryngeal dystonia

Abstract

Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

Evidence for Auditory-Motor Impairment in Individuals With Hyperfunctional Voice Disorders

“…In the 1950s, SD was widely believed to be caused "by psychoneurosis from either occupational stress or emotional trauma" (Arnold, 1959, p. 161, as cited in Aronson, 1990, a belief that persisted for decades thereafter (Aminoff, Dedo, & Izdebski, 1978). However, it is now known that SD is a focal dystonia of the larynx, a motor control disorder characterized by abnormal processing of somatosensory feedback (Termsarasab et al, 2016), which continues to lead to research aimed at improving its assessment and treatment. Thus, despite the limited sample size in the current study, the results suggest that much more research is needed to fully delineate the true etiology of hyperfunctional voice disorders to develop unbiased and effective assessments and interventions.…”

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

“…Similar to the procedures described earlier (Casanova et al 2007; Simonyan and Ludlow 2012; Termsarasab et al 2016), each patient’s VBM dataset (i.e., a smoothed modulated for the non-linear components DARTEL warped segmented gray matter image) was transformed from the MNI standard space into the Talairach-Tournoux standard space using @auto_tlrc program of AFNI software to match the space transformation of the fMRI dataset (i.e., beta coefficients of functional activation during symptomatic sentence production). To create a single 3D+subjects volume for each of the VBM and fMRI datasets, the respective images were concatenated across all subjects in each group.…”

Neuroimaging Applications in Dystonia

“…Studies examining the effects of botulinum toxin injections on brain activity in patients with focal dystonia provided largely controversial results, showing either modulated or non-modulated brain activity following the treatment (Ali et al, 2006; Dresel et al, 2011; Haslinger et al, 2005; Nevrly et al, 2018). On the other hand, subclinical abnormalities in sensory discrimination were described as a mediational endophenotype of dystonia (Hutchinson et al, 2013) and linked to alterations in primary somatosensory and middle frontal cortices (Termsarasab et al, 2016). Importantly, differential associations between abnormal sensory discrimination and functional abnormalities were observed depending on the phenotype and genotype of dystonia, including greater cerebellar involvement in familial laryngeal dystonia cases and greater putaminal and cortical sensorimotor inclusion in different phenotypes of laryngeal dystonia (Termsarasab et al, 2016).…”

“…On the other hand, subclinical abnormalities in sensory discrimination were described as a mediational endophenotype of dystonia (Hutchinson et al, 2013) and linked to alterations in primary somatosensory and middle frontal cortices (Termsarasab et al, 2016). Importantly, differential associations between abnormal sensory discrimination and functional abnormalities were observed depending on the phenotype and genotype of dystonia, including greater cerebellar involvement in familial laryngeal dystonia cases and greater putaminal and cortical sensorimotor inclusion in different phenotypes of laryngeal dystonia (Termsarasab et al, 2016). …”