title: Cervical dystonia: a disorder of the midbrain network for covert attentional orienting.
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.
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College Dublin , Dublin , Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Department of Developmental Physiology, National Institute for Physiological Sciences , Okazaki , Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isa
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College Dublin , Dublin , Ireland.
authors.forename: Anna
authors.initials: A
authors.lastname: Molloy
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College Dublin , Dublin , Ireland.
authors.forename: Okka
authors.initials: O
authors.lastname: Kimmich
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College Dublin , Dublin , Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Neurophysiology, Beaumont Hospital , Dublin , Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Molloy
authors.affiliation: Cork University Hospital , Cork , Ireland.
authors.forename: Helena
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Neurology, Beaumont Hospital , Dublin , Ireland.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Healy
authors.affiliation: Dublin Neurological Institute, Mater Misericordiae Hospital , Dublin , Ireland.
authors.forename: Tim
authors.initials: T
authors.lastname: Lynch
authors.affiliation: Department of Statistics, Trinity College Dublin , Dublin , Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin , Dublin , Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Butler
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin , Dublin , Ireland.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital , Dublin , Ireland.
authors.forename: Richard
authors.initials: R
authors.lastname: Walsh
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College Dublin , Dublin , Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Riordan
keywords: GABA; cervical dystonia; covert attention; superior colliculus; temporal discrimination