Pathophysiology
Roger Albin wrote a very thoughtful review of Tourette syndrome as "a disorder of the social decision-making network" \citep{29053770}. Beste and MĂĽnchau describe tics in the context of the Theory of Event Coding, which describes the brain's bidirectional pairing of stimulus and movement \citep*{29278288}. They note the salience of urges to most tic patients, and the fact that most tics are individually relatively normal movements, but occur repeatedly and out of context. Similarly, \citet{Shafer2017} focus on the strong connections between movement and sensory function to propose a theory that encompasses both the development of stereotypies as part of typical development and their persistence in maladaptive forms.
Animal models
A special issue on animal models of TS appeared in the Journal of Neuroscience Methods \citep*{29038076}. Articles reviewed gait and sensorimotor function in the D1CT-7 mouse model of Tourette syndrome \citep{28099872}, stress mediating the timing of abnormal movements in animal models \citep*{Godar2017123}, and chemogenetic and optogenetic models \cite{28756273}. Deer mice have behavior that has been discussed as a natural model of OCD \citep{29214602}.
Recently postnatal ablation of the TrkB receptor in cells expressing parvalbumin was shown to produce dramatic changes in cortex and cerebellum and "profound hyperactivity, stereotypies, motor deficits and learning/memory defects" \citep{28968898}. This result may help explain why autopsies in TS show a lower number of parvalbumin-containing interneurons in the striatum, but this model also produces much more substantial neuroanatomical changes than are seen in TS.
A gene identified in human OCD, slc1a1, which codes an excitatory amino acid transporter, was altered in mice to prevent its expression and function \citep{28507136}. The loss of this protein resulted in mice with reduced extracellular dopamine concentrations and reduced movement and stereotypic behavior after challenge with amphetamine or a dopamine D1 receptor agonist. Restoring the gene's expression in the midbrain, but not in the striatum, partially rescued the exogenous dopamine-induced stereotypies. This research is important for its direct links to human illness and its anatomical specificity, and lends additional support to testing dopamine D1 antagonists in TS (see Medication section, below).
New insights from computational modelling
Using the neurophysiological data obtained from a TS animal model of pharmacological striatal disinhibition, \citet{28358814} proposed a computational model of the basal ganglia-cerebellar-thalamo-cortical system to address the mechanisms of motor tic generation in Tourette syndrome. Overall, the model suggested that interplay between dopaminergic signal and cortical activity triggered the occurrence of a tic and was able to predict the number of tics generated when striatal dopamine increases and when the cortex is externally stimulated. \citet*{28734459} further discussed the role of tonic and phasic dopamine in tics learning and expression. Based on the existing literature of habit formation and reinforcement learning in TS, the authors proposed a model of tics as exaggerated and persistent motor habits reinforced by aberrant, increased phasic dopamine responses. According to this model, tonic dopamine release would serve to amplify the tendency to execute learned tics. The authors also proposed the mechanism of antipsychotics’ action on tics: increased activity of indirect pathway due to antipsychotic administration could result in tic reduction, but at the same time potentially also could increase the propensity for reinforcing tics due to plasticity in the indirect pathway. In contrast, the authors also suggested that low-dose dopamine agonists could decrease both phasic and tonic dopamine and thus reduce both tic learning and tic expression. Both of these reports assume increasing tics with increasing dopamine concentrations, an assumption that seems to contradict observations that tics do not worsen with exogenous levodopa \cite{kj2013,Black2000} nor improve with development of Parkinson disease \citep{Shale1986,Kumar1997,Martinez-Torres2009}. Furthermore, low-dose pergolide in children and adolescents with TS that reduced tic severity suppressed prolactin rather than increasing it, consistent with overall enhancement of dopamine transmission, at least in the hypothalamic-pituitary dopaminergic pathway \citep{sethuraman2000,10746603}.
Based largely on available functional anatomical studies, \citet{29017141} also proposed a computational model of premonitory urges in TS. According to this model, premonitory urges and in particular their termination, like termination of other aversive stimuli, might elicit positive prediction errors, supported by phasic dopamine release that would then reinforce tics. The insula may play a central role in aversive feeling associated with premonitory urges and their learned negative value. The insula might send this information via direct or indirect projections to dopamine neurons, which might use it for calculation of the positive prediction errors that occur with termination of the premonitory urge. In short, the authors provide a more detailed neurobiological explanation for the classic model that premonitory urges may strengthen tics through negative reinforcement.