Figure 2. Models of Tourette syndrome pathophysiology.
(A) Cortico-basal ganglia networks and Tourette syndrome clinical characteristics. Distinct cortico-basal ganglia networks are related to tics (sensorimotor network [orange]) and comorbidities (associative and limbic networks [grey]) in Tourette syndrome. (B) Neuropathological underpinnings of Tourette syndrome: stereological cellular count in post-mortem tissue revealed different cellular distributions in the basal ganglia of individuals with Tourette syndrome (3 patients, mean [SEM] age 42·0 [11·9] years) compared with controls (5 healthy controls, mean [SEM] age 60·0 [9·7] years; left panel), with fewer inhibitory GABAergic cells (red circle) and cholinergic cells (green hexagon) within the striatum in Tourette syndrome (5 patients, mean [SEM] age 43·0 [3·6] years) compared with 5 controls mean [SEM] age 61·8 [4·3] years (right panel). (C) Model of relationship between premonitory urges and tics: abnormal interoceptive information processing (insular cortex; blue area) and exteroceptive processing (sensorimotor cortex; pink areas) results in genesis of premonitory urges (insular cortex), leading to action initiation (via anterior cingulate cortex; green area) and subsequent tic execution (via cortico-basal ganglia sensorimotor network (as shown in A). Acc=anterior cingulate cortex. Ach+=cholinergic interneurons of the striatum. ADHD=attention deficit hyperactivity disorder. GABA Pav+=GABAergic parvalbumin-positive interneurons of the striatum. GPi=globus pallidus internus. GPe=globus pallidus externus. Ins=insular cortex. MSN=medium spiny neurons. OCD=obsessive-compulsive disorder. OFC=orbitofrontal cortex. SM=sensorimotor cortex. B (left) has been adapted from Kalanithi and colleagues51 and B (right) from Kataoka and colleagues52.