What is a possible model of tic production in the pathophysiology of Tourette syndrome (TS) and other tic disorders?

Updated: May 30, 2019
  • Author: William C Robertson, Jr, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP  more...
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Answer

Knowledge about primate basal ganglia anatomy and physiology has been summarized (see the image below). [100, 101, 102] In this view, motor patterns are generated in the cerebral cortex and brain stem. Performance of a specific intended movement includes not only selection of the desired movement but also inhibition of antagonistic movements and of similar movements of neighboring body parts.

Tourette syndrome and other tic disorders. Schemat Tourette syndrome and other tic disorders. Schematic of the hypothetical reorganization of the basal ganglia output in tic disorders, with excitatory projections (open arrows) and inhibitory projections (solid arrows). Line thickness represents the relative magnitude of activity. When a discrete set of striatal neurons becomes active inappropriately (right), aberrant inhibition of a discrete set of internal segment of globus pallidus (GPi) neurons occurs. The abnormally inhibited GPi neurons disinhibit thalamocortical mechanisms involved in a specific unwanted competing motor pattern, resulting in a stereotyped involuntary movement.

The basal ganglia are organized so as to inhibit, or apply a "brake" to these undesired motor programs. Normally, the basal ganglia allow selective release of the brake from the desired action. Tics may result from a defect in this braking function. This may be caused by an episode of overactivity in a focal subset of striatal neurons, perhaps in the striatal matrisomes identified by Graybiel and colleagues. [103] The episodic focal overactivity may result from any of various mechanisms acting at any of various locations from cortex to thalamus.

Dopaminergic innervation of striatum has several characteristics that would allow generation of such abnormal epochs of striatal activity; these include dopamine's modulation of the resting membrane potential set point and the influence of dopamine on long-term potentiation or long-term depression (relatively long lasting changes in neuronal excitability based on the prior neuronal inputs).

Finally, this theory is largely derived from studies of the motor circuit involving motor cortex, striatum, internal pallidum, subthalamic nucleus, and ventral thalamus. However, parallel neuronal circuits influence other regions of frontal cortex, including orbitofrontal, medial prefrontal, and dorsolateral prefrontal cortex. These pathways are relatively separated in the cortex, yet they physically course closer together in the basal ganglia, thalamus, and midbrain.

Lesional and neuroimaging data in individuals with OCD or ADHD implicate abnormalities in nonmotor regions of frontal cortex. Possibly the frequent, but not uniform, occurrence of these symptom complexes in patients with tics represents processes of similar pathology but overlapping anatomy (see image below).


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