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.

Keywords: Brain imaging; Endophenotype; Sensory processing.

Fig. 1

(A, C) Visual temporal discrimination threshold (TDT) Z-scores and (B, D) tactile spatial discrimination threshold (SDT) Z-scores in healthy controls and patients with LD. Z-scores equal or greater than 2.0 were considered abnormal (indicated by a horizontal dotted line). The number of subjects with abnormal TDT Z-scores/the total number of subjects per each group is demonstrated at the top of each distribution plot. For the range of values, see Table 2.

Fig. 2

Associations of abnormal TDT values with gray matter volume (A, B) and functional brain activation during speech production (C) across all LD patients. Z-scores equal or greater than 2.0 were considered abnormal. The color bar indicates the r values.

Fig. 3

Significant correlations of abnormal TDT with brain function and structure in LD patients. Top panel: In patients with sporadic and familial LD, abnormal TDT showed significant relationships with gray matter volume (A), resting-state brain activity (B), and brain activity during symptomatic speech production (C, D). Panel (C) shows regions of spatial overlap of these correlations between the two patient groups; Panel (D) shows additional regions of distinct correlations in each group. Bottom panel: In patients with ADLD and ABLD, abnormal TDT showed significant relationships with gray matter volume (E), resting-state brain activity (F, G), and brain activity during symptomatic speech production (H, I). Panels (F, H) show regions of spatial overlap of the corresponding correlations between the two patient groups. Panels (G, I) show additional regions of corresponding distinct correlations in each group. The color bars represent distinct correlations in sporadic (S), familial (F), ADLD (AD) and ABLD (AB) patients as well as common correlations between sporadic and familial patients (S × D) and between ADLD and ABLD patients (AD × AB). For the direction of correlations (positive and negative), see Table 3, Table 4.