Table 2.

An outline summary of some of the more important experimental evidence from clinical and animal studies supporting the hypothesis that both abnormal temporal discrimination and adult-onset isolated focal dystonia are due to a disorder of reflex covert orienting caused by defective GABAergic inhibition in the superior colliculus.

Hypothesis: pathological disinhibition in the midbrain network for covert attentional orienting due to deficient GABAergic activity causes

(a) Subclinically, abnormal temporal discrimination due to disordered visual processing in the SLSC

(b) Clinically, cervical dystonia due to disinhibited prolonged burst activity of cephalomotor neurons in the DLSC

Key observations in support of the hypothesis

Sensory aspects

(1) The midbrain network for covert attentional orienting is a primitive, highly conserved system for detecting salient environmental change, inspecting the change, and responding rapidly and appropriately

(2) Wide field visual sensory neurons in the SLSC, via the retinotectal pathway, detect environmental visual change and respond by transient discharges to the pre-motor neurons for saccade generation and head turning

(3) Focal inactivation of the SLSC causes loss of covert visual attention in the visual field represented by the inactivated part of the SLSC

(4) Inhibitory GABAergic activity (within the superior colliculus and from the SNpr) limits the duration of the transient response in visual sensory neurons in the SLSC

(5) A moving or sudden luminant visual stimulus elicits a time-locked electromyographic response in cervical muscles involved in ipsilateral head turning

Motor aspects

(1) Movement is initiated by the striatum through release from the tonic inhibition exerted by the SNpr. A core neurophysiological feature of dystonia is reduced inhibition at all levels of the CNS; the most probable cause is defective GABAergic inhibition

(2) The oculomotor and cephalomotor pre-motor neurons of the DLSC for saccade generation and head turning are tonically inhibited by the SNpr. Release from that inhibition allows prolonged burst discharges of premotor neurons

(3) Oculomotor premotor neurons are gated by omnipause neurons; the cephalomotor premotor neurons are not gated

(4) Stimulation of cephalomotor neurons in the DLSC causes ipsilateral head turning in monkeys via the tectospinal and tecto-reticulospinal fiber tracts terminating in the cervical cord

(5) A unilateral lesion of the SNpr in macaques causes a movement disorder resembling cervical dystonia. A further lesion in the superior colliculus abolishes/attenuates the movement disorder

This argument is expanded and fully referenced in the text. AOIFD, adult-onset isolated focal dystonia; DLSC, intermediate and deep laminae of the superior colliculus; SLSC, superficial laminae of the superior colliculus; SNpr, substantia nigra pars reticulata; TDT, temporal discrimination threshold.