Cervical dystonia: a disorder of the midbrain network for covert attentional orienting.

Michael Hutchinson,Okka Kimmich,Tadashi Isa,Richard B Reilly,Daniel G Healy,Cathal Walsh,Sean Oâ€™Riordan,Fiona Molloy,Anna Molloy,Tim Lynch,Laura Williams,Helena Moore,John Butler,Richard Walsh

doi:10.3389/fneur.2014.00054

Abstract

While the pathogenesis of cervical dystonia remains unknown, recent animal and clinical experimental studies have indicated its probable mechanisms. Abnormal temporal discrimination is a mediational endophenotype of cervical dystonia and informs new concepts of disease pathogenesis. Our hypothesis is that both abnormal temporal discrimination and cervical dystonia are due to a disorder of the midbrain network for covert attentional orienting caused by reduced gamma-aminobutyric acid (GABA) inhibition, resulting, in turn, from as yet undetermined, genetic mutations. Such disinhibition is (a) subclinically manifested by abnormal temporal discrimination due to prolonged duration firing of the visual sensory neurons in the superficial laminae of the superior colliculus and (b) clinically manifested by cervical dystonia due to disinhibited burst activity of the cephalomotor neurons of the intermediate and deep laminae of the superior colliculus. Abnormal temporal discrimination in unaffected first-degree relatives of patients with cervical dystonia represents a subclinical manifestation of defective GABA activity both within the superior colliculus and from the substantia nigra pars reticulata. A number of experiments are required to prove or disprove this hypothesis.

Highlights

Cervical dystonia, characterized by sustained or intermittent neck muscle contractions causing abnormal head movements, is the most common form of adult-onset idiopathic isolated focal dystonia (AOIFD) and may be sporadic or familial [1]
HYPOTHESIS We postulate that cervical dystonia is a disorder of a midbrain network for covert attentional orienting involving both the sensory and motor laminae of the superior colliculus
We postulate that cervical dystonia and abnormal temporal discrimination are both due to a disorder of the midbrain network for attentional orienting, caused by impaired GABAergic mechanisms of inhibition of sensorimotor processing within the superior colliculus

Summary

INTRODUCTION

Cervical dystonia, characterized by sustained or intermittent neck muscle contractions causing abnormal head movements, is the most common form of adult-onset idiopathic isolated focal dystonia (AOIFD) and may be sporadic or familial [1]. In patients with cervical dystonia, a number of neurophysiological and neuroimaging abnormalities have been described as endophenotypes implying a relationship to causal mechanisms [reviewed in Ref. Shared pathological mechanisms for both disordered temporal discrimination and cervical dystonia have become evident over the past 10 years from highly sophisticated piecemeal investigations in diverse disciplines including primate and sub-primate neurophysiology, anatomy, chemistry, psychology, and clinical research. Using this evidence, we propose a unified theoretical model to explain the etiopathogenesis of cervical dystonia.

Cervical dystonia and the superior colliculus

CONTROL OF CEPHALOMOTOR OUTPUT FROM THE SUPERIOR COLLICULUS

Findings

CONCLUSION