Two other studies of interest were conducted on children with TS. One study \citep{Hsu_2023} investigated microstructural changes, while the other \citep{Xin_2023} examined alterations in dynamic brain functional networks. The first study \citep{Hsu_2023} compared two cohorts comprising 30 individuals each (healthy controls versus individuals with pure and treatment-naïve TS). Utilizing diffusion spectrum imaging metrics, with a specific focus on the cortico-striato-thalamocortical network, the authors did not observe any significant alterations in several segments of the network, but they identified that TS was associated with elevated generalized fractional anisotropy in the right frontostriatal tract (which also correlated with tic severity) and in the bilateral thalamic radiation. In the second study \citep{Xin_2023}, temporal properties of functional connectivity were assessed by comparing 36 male individuals with TS to 27 matched healthy controls. Notably, a dysfunctional functional state was identified in TS, correlating with tic severity. This state was characterized by over-connection within the subcortical, sensorimotor, and default mode networks, coupled with under-connection in the salience and executive control networks. Additionally, TS was associated with higher temporal variability in functional networks compared to controls. Although employing different methodologies, both studies converged to underscore the dysfunction of the basal ganglia in TS, thereby enriching our comprehension of brain functioning in children with the disorder.
Finally, using tractography in 58 TS patients and 35 healthy volunteers, Temiz and colleagues showed a significantly increased limbic cortical connectivity in TS patients \citep{Temiz2023}. In particular, connectivity of the left insular-subthalamic nucleus was positively correlated with higher impulsivity and anxiety scores.
Animal models
TS pathophysiology has been linked to a disturbed migration of cholinergic interneurons into the striatum \citep{Kataoka2010}, disturbed dopaminergic transmission \citep{Maia2018}, and, in rare monogenetic forms, a loss-of-function in the SLITRK1 gene \citep{Abelson2005}. Du and colleagues attempt to link all three in a mouse model where SLITRK1 si-RNA was injected into the dorsal striatum, and they observed a number of behavioral, neurochemical and electrophysiological abnormalities compatible with TS in humans. They conclude that targeting the function of striatal cholinergic interneurons might represent as a potential therapeutic strategy for TS \citep{Du2023}.