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Despite their frequency, the underlying pathophysiology of tics\/Tourette syndrome remains unknown. In this review, we discuss a variety of controversies surrounding the pathophysiology of tics, including the following: Are tics voluntary or involuntary? What is the role of the premonitory urge? Are tics due to excess excitatory or deficient inhibition? Is it time to adopt the contemporary version of the cortico-basal ganglia-thalamocortical (CBGTC) circuit? and Do we know the primary abnormal neurotransmitter in Tourette syndrome? Data from convergent clinical and animal model studies support complex interactions among the various CBGTC sites and neurotransmitters. 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