SCIENTIfIC REpoRts | 7: 16753 | DOI:10.1038/s41598-017-17074-x
Disrupted superior collicular
activity may reveal cervical
dystonia disease pathomechanisms
Eavan M. Mc Govern
, Owen Killian
, Shruti Narasimham
, Brendan Quinlivan
John B. Butler
, Rebecca Beck
, Ines Beiser
, Laura W. Williams
, Ronan P. Killeen
, Sean O’Riordan
, Richard B. Reilly
& Michael Hutchinson
Cervical dystonia is a common neurological movement disorder characterised by muscle contractions
causing abnormal movements and postures aecting 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 aected patients and in relatives harbouring a disease-specic endophenotype (abnormal temporal
discrimination). The study participants were 16 cervical dystonia patients, 16 unaected rst-degree
relatives with abnormal temporal discrimination, 16 unaected rst-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) signicantly reduced superior
collicular activation for whole brain and region of interest analysis; (ii) a statistically signicant 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 ndings, which align with animal models of cervical dystonia, shed new light on
pathomechanisms in humans.
Cervical dystonia is a hyperkinetic movement disorder characterised by sustained or intermittent muscle contrac-
tions causing abnormal movements and postures
. It is the most common phenotype of adult onset focal isolated
dystonia (AOIFD), of which several phenotypes exist. e pathogenesis and the neural networks underpinning
this condition remain unknown. While cervical dystonia is considered to be essentially due to basal ganglia dys-
, mounting evidence indicates a wider network disorder involving cortical, subcortical and cerebellar
. Understanding how these various structures interact with the basal ganglia is important when consid-
ering possible pathomechanisms in cervical dystonia
. Subcortical structures including the midbrain interstitial
nucleus of Cajal, midbrain neural integrators and the superior colliculus form part of this network and have been
implicated in its pathogenesis
. Alterations in basal ganglia-brainstem and cerebellum-brainstem connections
are also considered important
. Disruption of inhibitory input to the superior colliculus in macaques results in a
primate model of cervical dystonia
. While decient inhibition has long been considered important in the patho-
genesis of dystonia
, how the superior colliculus ts into this paradigm has yet to be studied in humans.
Cervical dystonia is postulated to be a poorly penetrant autosomal dominant condition
. However caus-
ative genes have been identied in <1% of cases
. is shortfall in gene discovery has stimulated a search
for endophenotypes and alternative pathomechanistic theories
. Aberrant sensorimotor plasticity has been
linked to the pathogenesis of dystonia
, in particular focal-hand dystonia, a phenotype of AOIFD frequently
Department of Neurology, St Vincent’s University Hospital Dublin, Dublin, Ireland.
School of Medicine & Medical
Science, University College Dublin, Dublin, Ireland.
Trinity Centre for Bioengineering, Trinity College, The University
of Dublin, Dublin, Ireland.
School of Engineering, Trinity College, The University of Dublin, Dublin, Ireland.
of Medicine, Trinity College, The University of Dublin, Dublin, Ireland.
School of Mathematical Sciences, Dublin
Institute of Technology, Kevin St, Dublin, Ireland.
Department of Neuroradiology, St. Vincent’s University Hospital,
Elm park, Dublin, Ireland.
Department of Neuropathology, Beaumont Hospital, Dublin, Ireland. Correspondence
and requests for materials should be addressed to E.M.M.G. (email: email@example.com)
Received: 16 May 2017
Accepted: 21 November 2017
Published: xx xx xxxx