Pathophysiology of tic disorders

Abstract

Tics are the defining symptom of Tourette syndrome and other tic disorders (TDs); however, they form only a part of their overall symptoms. The recent surge of studies addressing the underlying pathophysiology of tics has revealed an intricate picture involving multiple brain areas and complex pathways. The myriad of pathophysiological findings stem, at least partially, from the multifaceted properties of tics and the disorders that express them. Distinct brain pathways mediate the expression of tics, whereas others are involved in the generation of the premonitory urge, associated comorbidities, and other changes in brain state. Expression of these symptoms is controlled by additional networks underlying voluntary suppression by the patient or those reflecting overall behavioral state. This review aims to simplify the complex picture of tic pathophysiology by dividing it into these key components based on converging data from human and animal model studies. Thus, involvement of the corticobasal ganglia pathway and its interaction with motor, sensory, limbic, and executive networks in each of the components as well as their control by different neuromodulators is described. This division enables a focused definition of the neuronal systems involved in each of these processes and allows a better understanding of the pathophysiology of TDs as a whole.

Neurobiology of the Premonitory Urge in Tourette’s Syndrome: Pathophysiology and Treatment Implications

“…The exact pathophysiology and brain mechanisms underlying tic expression are not fully understood, however converging evidence points toward a role for dysfunction of dopaminergic transmission within cortico-striato-cortico-frontal circuitries as a key etiological pathway {11,12}. TS is a genetically heterogeneous condition, with epidemiological evidence suggesting an association with pre- and peri-natal problems and a possible role for post-streptococcal autoimmune dysfunction in the etiopathogenesis of at least a subgroup of patients with TS {13,14}, although this remains highly controversial.…”

Tics and Tourette syndrome

“…The pathophysiology of tics is not well understood but is believed to involve abnormalities in the pathways between the cerebral cortex and basal ganglia, leading to a background neuronal disinhibition in both motor and limbic systems . Aligning with the clinical association that sensory features are common, sensory limbic and executive corticostriatal loops have also been demonstrated to be affected . Biochemically, TS appears to result from alteration in both dopaminergic modulation and histaminergic transmission, although other neurotransmitter systems may also be involved.…”

Deep Brain Stimulation of the H Fields of Forel Alleviates Tics in Tourette Syndrome

“…Thus, to our knowledge, this is the first study reporting successful tic suppression following functional neurosurgery of the H fields of Forel, in particular field H1, in a retrospective uncontrolled trial of two patients. Successful stimulation can be attributed to the central position of Forel's fields, relaying sensorimotor, associative, and limbic information between core anatomical structures involved in the pathophysiology of TS (Yael et al, 2015). Field H1 can therefore be considered a “bottleneck” both functionally and anatomically (Figure 1).…”

“…Among functional parallel circuits, the motor pathway is the principal network involved in tic generation (Yael et al, 2015). Premonitory urges as well as comorbid conditions on the other hand are mediated by sensory, associative and limbic pathways.…”