Objective: To investigate resting state functional networks across cervical dystonia patients and their unaffected relatives with and without abnormal temporal discrimination thresholds (TDTs) based on independent component analysis and graph theoretical analysis of resting state functional magnetic resonance imaging data.

Background: Cervical Dystonia is hypothesised to be a functional network disorder associated with aberrant gamma-amino-butyric acid levels in the mid-brain. While an abnormal TDT is an endophenotype for cervical dystonia, the functional networks involved in temporal discrimination and their links to the pathomechanism of cervical dystonia remain unexplored. Resting state functional studies may elucidate the mechanisms of abnormal TDTs in unaffected relatives; we postulate functional connectivity aberrations will be similar in patients and unaffected relatives with abnormal TDT.

Methods: We employed independent component analysis followed by dual regression and graph theory analysis to examine and compare large-scale topology of functional brain networks using resting state functional magnetic resonance imaging data acquired from 64 age and sex matched participants (16 in each group – cervical dystonia patients, unaffected first degree relatives with normal temporal discrimination, unaffected first degree relatives with normal temporal discrimination and healthy controls).

Results: On comparison of the functional connectivity and network architecture across the four cohorts, first degree unaffected relatives and patients showed similar (i) widespread functional network reorganization and significant differences in connectivity (p<0.05) in the Visual, Basal Ganglia (BGN), Cerebellum, Mid-Brain and Sensorimotor (SMN) resting state networks (ii) significant abnormalities in the inter-connectivity between the BGN and SMN (iii) SMN connectivity correlated significantly with TDT values (iv) significant differences in network properties at the nodal level compared to healthy controls (reduced clustering coefficient and increased number of shortest paths).

Conclusions: Our results suggest that first degree unaffected relatives with abnormal TDT manifest some common functional network aberrations as observed in cervical dystonia patients, shedding new light on the pathomechanisms of this disorder.

References: Hutchinson, M., Isa, T., Molloy, A., Kimmich, O., Williams, L., Molloy, F., . . . O’Riordan, S. (2014). Cervical Dystonia: A Disorder of the Midbrain Network for Covert Attentional Orienting. Frontiers in Neurology, 5. doi:10.3389/fneur.2014.00054

Battistella, G., Termsarasab, P., Ramdhani, R. A., Fuertinger, S., & Simonyan, K. (2015). Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks. Cerebral Cortex. doi:10.1093/cercor/bhv313

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MDS Abstracts - https://www.mdsabstracts.org/abstract/associations-between-functional-networks-and-temporal-discrimination-thresholds-in-cervical-dystonia-patients-and-their-unaffected-relatives/