Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients

Abstract

Background: An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms.Objective: To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD.Methods: Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses.Results: Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination.Conclusion: Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.

Visual Sensory Processing is Altered in Myoclonus Dystonia

“…However, we found the correlation of greater putaminal volumes with severity of the myoclonus in DYT‐ SGCE ‐non‐DBS. Interestingly, unaffected relatives of cervical dystonia with an abnormal TDT threshold had abnormally high regional homogeneity signaling in the thalamus, suggesting a close implication of this structure in TDT. DYT‐ SGCE is a neurodevelopmental disorder with an early onset in most patients, with a known interaction between the development and phenomenology of the movement disorder .…”

Visual temporal discrimination is impaired in patients with migraine without aura

“…Observations made especially in patients with dystonia have indicated that temporal discrimination thresholds are prolonged even in relatives of those who did not have dystonia. It is assumed that this may be an endophenotypic marker in patients with multigenic inheritance, such as dystonia 43 . Considering the studies suggesting that migraine is inherited depending on genetic predisposition, 44 the value of the VTDT as an endophenotypic marker in patients with migraine needs to be investigated by comprehensive studies with more participants.…”

“…It is assumed that this may be an endophenotypic marker in patients with multigenic inheritance, such as dystonia. 43 Considering the studies suggesting that migraine is inherited depending on genetic predisposition, 44 the value of the VTDT as an endophenotypic marker in patients with migraine needs to be investigated by comprehensive studies with more participants.…”