Tactile Temporal Discrimination Is Impaired in Myoclonus‐Dystonia

The temporal discrimination threshold (TDT), defined as the shortest interval at which two sequential sensory stimuli are perceived as being asynchronous, is usually assessed using a tactile or visual modality. Increased TDT was previously described in various forms of adult-onset focal dystonia. TDT was suggested to be a mediational endophenotype for dystonia as it is abnormal in unaffected first-degree relatives, and there is no correlation between TDT and dystonia severity. Myoclonus-dystonia, caused by mutation of the epsilonsarcoglycan gene (DYT-SGCE), is clinically characterized by myoclonus associated with mild dystonia, likely underpinned by a dysfunction of the cerebello-thalamo-cortical and striatopallido-thalamo-cortical pathway. We showed abnormal threshold for the visual TDT in the most severe DYT-SGCE patients treated with deep brain stimulation of the internal globus pallidus. The existence of abnormalities in another sensory modality remains unclear. We used the tactile temporal discrimination task and stair-case procedure (Fig. 1A and Supplementary Data) for assessing the temporal discrimination in 23 DYT-SGCE patients compared to 25 age-, gender-, and educational level-matched healthy volunteers (HV) (Supplementary Table S1). We also evaluated a tactile perception threshold (TT), which refers to the lowest tactile stimuli intensity the subject could perceive. Both TT and TDT were measured on the dominant hand of the subjects. We found no differences between the groups in TT threshold (all P > 0.05), suggesting absence of the deficit in tactile sensitivity per se in DYT-SGCE. As shown in the Figure 1B, DYTSGCE (mean ± SEM, 110.22 ± 9.15 ms) showed increased TDT compared to HV (mean ± SEM, 82.20 ± 5.71 ms; F1,47 = 6.99, P = 0.01). The TDT was not related to any clinical (BFM, UMRS, psychiatric comorbidities and medication) or demographic (gender, laterality, age, years of education) measures. In conjunction with previous results on visual TDT, our results suggest a widespread disturbance of the sensory information processing for DYT-SGCE patients. Basal ganglia and sensori-motor cortex are known to be involved in tactile TDT processing. In dystonia, increased TDT was related to reduced activity of inhibitory circuits within the primary somatosensory cortex. DYT-SGCE patients have a normal intracortical inhibition but lower excitability of the motor cortex and therefore, dysfunction of cortical inhibitory circuits as mechanism of TDT increase cannot be ruled out. Other regions involved with tactile simultaneity judgment are the inferior parietal lobule and striatum, the latter specifically coding time interval between tactile stimuli. Basal ganglia remain the main nodes underlying TDT abnormalities in other dystonias. In addition, the cerebellum, a key structure in the pathogenesis of myoclonus-dystonia, has also been implicated in time perception and in TDT disturbances of patients with Parkinson’s disease, degenerative cerebellar ataxia, and cervical dystonia. Consequently, in DYT-SGCE, increased tactile TDT might be driven by a dysfunction of cerebello-striato-cortical network. However, the exact role of each of these structures still remains to be investigated. In addition to an abnormal plasticity of the motor cortex and abnormal cerebellar learning, impaired temporal discrimination appears to belong to the various neurophysiological abnormalities shared by myoclonus-dystonia and other forms of dystonia.