A research consortium in Germany has recently proposed that tics may correspond to altered perception-action binding \citep{Beste2018}. \citet{Petruo2018} provide a first experimental demonstration in 35 adolescents with TS and 39 healthy controls using a Go/no-go task and subsequent EEG analysis, providing support for the idea that stimulus-action binding is stronger in patients with TS, and that "unbinding" may thus represent a useful therapeutic venue.
Inhibitory control in TS has been assessed in a myriad of different ways, with conflicting results. For instance, \citet{Mancini2018} report abnormal inhibitory function in patients with OCD, but no deficits in the TS group. Similarly, \citet{30485912} performed a clever study of a form of automatic motor inhibition. Exposure to a subliminal stimulus at an appropriate time prior to a supraliminal movement cue inhibits movement, a phenomenon called the negative compatibility effect (NCE). Here, 21 adults with TS and 21 tic-free controls performed similarly, suggesting that NCE is another form of experimental motor inhibition that appears normal in TS.
By contrast, the role of abnormal habit-learning has been posited as a cognitive marker of TS. It is yet unclear if tics would result from increased habit-learning, deficits in unlearning maladaptive behaviors, or a combination of both. \citet{Shephard2018} investigated implicit sequence learning in youth with TS with or without ADHD compared to tic-free youth with or without ADHD. Subjects with ADHD demonstrated impaired learning of a motor sequence learning task, while subjects with TS had mildly enhanced learning. However, they found evidence of "hyper-learning," in which subjects with TS had difficulty in unlearning the motor sequence task. Similarly, \citet{30292925} demonstrated slower unlearning (forgetting) of a visuomotor task in children and adolescents with TS. The role that impaired habit unlearning may play in TS warrants further investigation.
Adaptive functioning, a person's ability to function and organize themselves in daily life, has not been well-characterized in TS. Taylor et al. found that, in a TS sample, deficits in adaptive function were mostly driven by impaired executive function. ADHD and two or more comorbid conditions were associated with decreased adaptive function. More than half of the variance in this study was explained by deficits in executive function, rather than tics themselves. These results suggest that aggressive treatment of ADHD and comorbid diagnoses may be important in clinical management of TS \cite{murphy2018}.
Treatment
Psychological interventions
Group-based psychotherapeutic interventions for tics bear the promise of reduced costs and easier access to appropriate care, and several recent reports address this treatment option. One recent paper investigated the long term effects of group therapy on tic severity, quality of life and school attendance in 28 children with TS 12 months after completing HRT training or education (a follow up to the 2016 study, \cite{Yates2016}), showing positive effects in the long run but apparently without significant differences between both groups \cite{Dabrowski2018}. A Danish study investigated a combined ERP / HRT protocol comparing group with individual sessions (n=27 per group, n=54 total). The efficacy on decreasing tic severity was similar in both treatment arms \citep{Nissen2018}. Traditionally, ERP sessions (as compared to HRT / CBIT) were supposed to last for two hours, making them more difficult and expensive. In this study, session duration was shortened to one hour and shorter exposure was as effective, if not more, than the classic format \citep{van2018}. In another potential method for wider behavior therapy accessibility, \citet{Andr_n_2019} report preliminary results from a major study on therapist-supported, parent-guided, online behavior therapy for TS. Patients improved substantially (mean 75% with ERP, 55% with HRT), and the improvement persisted up twelve months later. The average therapist time was only 25 minutes per week.
Medication
Swedish treatment registries were searched to identify patterns of medication prescribing for almost 7000 patients with TS/CTD from 2005–2013 \citep{29870273}. Among other interesting findings, ADHD drugs, antidepressants, and hypnotics/sedatives were all prescribed more often than antipsychotics, for which there is much stronger evidence of efficacy.
\citet{Rizzo2018} provide the first direct comparison of pharmacotherapy with behavioral therapy in children and adolescents with TS / CTD. Both approaches were effective in reducing tics and improving quality of life; however, only pharmacotherapy was effective in reducing OC symptoms.
The D1 receptor antagonist ecopipam was compared to placebo in a double-blind, crossover, randomized controlled trial (RCT) in children and adolescents with TS \citep{chipkin2017}\citep{chipkin2018}. YGTSS total tic score (TTS) declined significantly more with the active drug. Another drug acting largely on dopamine, the VMAT2 inhibitor valbenazine, was tested in a phase IIb study in TS, but failed to meet the primary efficacy endpoint \citep*{syndrome2018}.
Neurosurgery
Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry
\citep{Martinez_Ramirez_2018}. This report summarizes information on 185 Tourette patients from 10 countries. Mean improvement in total YGTSS score was 40% at 6 months after
vs. before surgery, and 45% at 12 months. The difference between stimulation sites (CM-Pf, anterior GPi, posterior GPi) was not statistically significant. About a third of patients had side effects, mostly related to stimulation not surgery. A large, collaborative group is beginning a study using this database to investigate the optimal site for DBS via a 3D analysis (
link).
DBS in children remains controversial. Coulombe et al. review available data on DBS in "children" (ages 12-21) \citep{30497215}, and \citet{Smeets2018} discuss ethical considerations regarding DBS in TS patients under the age of 18.