AUTHOR=Narasimham Shruti , McGovern Eavan M. , Quinlivan Brendan , Killian Owen , Beck Rebecca , O’Riordan Sean , Hutchinson Michael , Reilly Richard B. 

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

JOURNAL=Frontiers in Integrative Neuroscience

VOLUME=Volume 13 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/integrative-neuroscience/articles/10.3389/fnint.2019.00008

DOI=10.3389/fnint.2019.00008

ISSN=1662-5145

ABSTRACT=Background
An abnormal temporal discrimination threshold in cervical dystonia is considered to be a mediational endophenotype; in unaffected relatives it is hypothesised 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 cervical dystonia 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 cervical dystonia, thereby illuminating the neural substrates of the link between temporal discrimination and cervical dystonia. 

Methods
Rs-fMRI data was analysed from two sex- and age-matched cohorts: 16 unaffected relatives of cervical dystonia 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.