Disrupted superior collicular activity may reveal cervical dystonia disease pathomechanisms

Eavan M Mc Govern,Richard B Reilly,Michael Hutchinson,Michael Farrell,Laura W Williams,Sean O’Riordan,Shruti Narasimham,Owen Killian,Ines Beiser,Brendan Quinlivan,Rebecca Beck,John B Butler,Ronan P Killeen

doi:10.1038/s41598-017-17074-x

Abstract

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected first-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participant’s superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) significantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically significant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These findings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans.

Highlights

Cervical dystonia is a hyperkinetic movement disorder characterised by sustained or intermittent muscle contractions causing abnormal movements and postures[1]
Aberrant sensorimotor plasticity has been linked to the pathogenesis of dystonia[8,23,24], in particular focal-hand dystonia, a phenotype of AOIFD frequently
Unaffected relatives and patients were selected in the present study to investigate the role of superior collicular dysfunction in cervical dystonia

Summary

Introduction

Cervical dystonia is a hyperkinetic movement disorder characterised by sustained or intermittent muscle contractions causing abnormal movements and postures[1]. While cervical dystonia is considered to be essentially due to basal ganglia dysfunction[1,2,3,4,5,6], mounting evidence indicates a wider network disorder involving cortical, subcortical and cerebellar regions[7,8,9]. Unaffected relatives with abnormal temporal discrimination (up to 50% of female relatives & 20% male relatives33) are hypothesised to be non-manifesting gene carriers This group may manifest similar alterations in brain activity to patients (without the complication of secondary effects due to motor manifestations). These unaffected relatives form an interesting study group because, by studying them one may examine disordered brain activation resulting from the endophenotype alone (an abnormal TDT) without the secondary effects from phenotype manifestation (cervical dystonia). A functional magnetic resonance imaging (fMRI) study revealed that looming stimuli (but not random stimuli) activated the superior colliculus[41]

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