The pathophysiology of tics; An evolving story

Harvey S. Singer, Farhan Augustine

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


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 figure). 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.

Original languageEnglish (US)
Pages (from-to)92-123
Number of pages32
JournalCurrent Drug Therapy
Issue number2
StatePublished - 2020


  • CBGTC circuits
  • Habitual behaviors
  • Neurotransmitters
  • Pathophysiology
  • Tics

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)


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