Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor
movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder
characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of
co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology
of tics/TS remains unknown.
Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically:
1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor
control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential
anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of
specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract
Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed
to provide: 1) an expanded understanding of individual components and the complex integration
of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved
with motor control; and 2) scientific data directly addressing each of the aforementioned controversies
regarding pathways, inhibition, classification, anatomy, and neurotransmitters.
Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach
is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the
motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a
tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed
toward the primary abnormality.