A monumental and definitive review (for the time being) on the immunology (immune pathways, neuroinflammation, microbiome) of brain development in general and TS in particular by one of the foremost specialists in the field \citep{Martino2020}. 

Title: "Metastable attractors explain the variable timing of stable behavioral action sequences"  Abstract: "Here, we focus on the observation that the timing of self-initiated actions shows large variability even when they are executed in stable, well-learned sequences. Could this mix of reliability and stochasticity arise within the same circuit? We trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), which is known to reflect trial-by-trial action timing fluctuations. Using hidden Markov models we established a robust and accurate dictionary between ensemble activity patterns and actions. We then showed that metastable attractors, representing activity patterns with the requisite combination of reliable sequential structure and high transition timing variability, could be produced by reciprocally coupling a high dimensional recurrent network and a low dimensional feedforward one."  \citep{Recanatesi_2020} (emphasis added)

Inhibiting parvalbumin-containing GABAergic neurons in a prefrontal-striatal circuit previously implicated in excessive habit generation (persistent rodent grooming to a tone before a drop of water on the face) impairs feedforward inhibition \citep{32029441}   (reviewed in TAA conference talk 2021-05-14)

Cagle and colleagues reported an interesting study based on LFP recording of both the centromedian thalamic nucleus and the primary motor cortex in 4 TS patients following bilateral deep brain stimulation surgery \citep{Cagle_2020}. They highlighted that beta power (12-30Hz) was reduced in the primary motor cortex after both a tic and a voluntary action, while low-frequency power (3-10Hz) was increased after a tic but not after a voluntary movement. They concluded to the identification of a tics’ specific signal within the centromedian thalamic nucleus which could be a target for developing closed-loop deep brain stimulation.

A vast resting-state EEG study comparing young (7-15 years old) TS patients, chronic tic disorders patients and HC revealed many interesting results \citep{Naro_2020}. Among them, they highlighted a disconnection of the fronto-parietal network which could contribute to TS motor symptomatology, while a sensorimotor disconnection was revealed for both TS and chronic tic disorders patients as related to tic severity only. In addition, they identified the dynamic of tics in both groups of patients as follow: (1) for TS patients only, tics are preceded by a gamma (30-70Hz) frequency activation and a beta2 (20-30Hz) frequency deactivation in the posterior cingulate cortex and the supplementary motor area; (2) for both, tics onset are associated with alpha (8-13Hz) and beta (13-30Hz) deactivation within the sensorimotor areas; (3) for TS patients only, tics are followed by a gamma (30-70Hz) and beta (13-30Hz) frequency activation in the left dorsolateral prefrontal cortex, while for chronic tic disorders patients they are followed by a delta (2-4Hz) and alpha (8-13Hz) deactivation within the posterior cingulate cortex. Therefore, the dynamic of tics in TS and chronic tic disorders patients are differently disturbed, and the fronto-parietal network disconnection result reinforces the known pathophysiology of TS as related to an impairment of the limbic, paralimbic and cortico-striatal-thalamo-cortical pathways.