To better understand the deficit in motor inhibitory control in TS, Indrajeet and colleagues used a recent alternative method (cancellable rise-to-threshold model, CRTT), which distinguishes between proactive (anticipation of a inhibition movement) and reactive (cancelation of a planned unwanted movement) inhibitory control \citep{Indrajeet2022}. They compared 63 patients with TS and 34 HC on an Emotional Stop Signal Task (ESST) and identified robust deficits in reactive control, but not in proactive control in TS. The TS group had difficulties in slowing down the speed of movement preparation, which they rectified by their intact ability to postpone the movement.

An EEG study assessing inhibitory control of frontal lobe regions,  which are important for motor inhibition in chronic tic disorders, was conducted using a stop signal task \citep{Zea2022}. Right superior frontal gyrus gamma event-related desynchronization (ERD) was elevated in patients with chronic tic disorders  during stop preparation. Elevated right superior frontal gyrus gamma ERD correlated with decreased tic severity, suggesting that right superior frontal gyrus gamma ERD may reflect a mechanism of tic suppression. Using magnetoencephalography, error-related negativity, an event-related potential component and an index of performance monitoring processes during simple stimulus-response tasks, was examined for changes in the performance monitoring system in TS \citep{Metzlaff2022}. The results suggest that increased motor control induced by conflict between high target task performance and tic suppression in TS patients may influence early error-related processing, and that TS patients may initially tend to process all responses as error responses. In the future, it is envisioned that electroencephalography will be useful as a biomarker in TS and in understanding the pathophysiology of tics.
Electrophysiology has also been discussed as a biomarker for tic disorders. TMS was also discussed including reduced short-interval intracortical inhibition at rest, which suggests a correlation with motor tic severity, shortened cortical silent period duration, increased intracortical facilitation, and decreased motor evoked-potential amplitude \citep{Jannati2022}. Using EEG as a biomarker for comprehensive behavioral intervention (CBIT), a randomized controlled trial was conducted to determine whether EEG coherence during Go/NoGo tasks correlated with CBIT outcomes \citep{Morand-Beaulieu2022}. No association was found between EEG coherence during the Go/NoGo task and changes in tic severity, suggesting that brain processes in the inhibition of motor responses do not play any role in CBIT. 
Electrophysiological studies were discussed as a possible therapeutic modality for tic disorders. Transcranial magnetic stimulation (TMS) as a treatment modality for tics has been discussed in several reviews. Repetitive TMS has shown to improve tic symptoms and tic comorbidities, and its safety has been confirmed \citep{Bejenaru2022}. Other review articles have discussed not only TMS but also on other electrophysiological modalities such as transcranial direct current stimulation (tDCS), peripheral nerve stimulation, and cranial electrotherapeutic stimulation for the treatment of tics \citep{Frey2022}. In contrast to repetitive TMS, tDCS, which works by applying a constant low current to electrodes attached directly to the scalp, is inexpensive, portable, and easy to implement. To date, results have been mixed and inconclusive as many studies have been open-label designs. Vagus nerve stimulation (VNS) treatment has also been reported to improve tic symptoms, but it is still unknown how VNS affects tic symptoms. Stimulation of peripheral nerves  (i.e., median nerve) with 12 Hz rhythmic pulses synchronized with mu-band oscillations in the brain has been reported to significantly reduce the frequency and severity of tics. CES is a small, portable device that stimulates the brain with a weak electric current and is being studied for its effectiveness in treating tic disorders.

Neuroimaging studies

On the topic of thalamic DBS, Baldermannan colleagues \citep{Baldermann_2022} used data of 15 operated TS patients. Concerning tic reduction (i) a positive relationship was observed for the functional connectivity between the activated tissue by DBS and the sensorimotor cortex, the bilateral insula and the inferior frontal cortex, and (ii) a negative relationship was described between the activated tissue and the cerebellum, the temporal and the orbitofrontal cortex, as well as with the ventral striatum.
From a purely pathophysiological viewpoint, three publications used MRI to identify abnormalities in TS. The first one \citep{Bharti_2022} highlighted that pure TS, as well as TS associated with OCD (both drug-naïve), were underpinned by an increased white matter fractional anisotropy in the corticospinal tract, the anterior thalamic radiations, the inferior longitudinal fasciculus and the corpus callosum, all correlated with tic severity. The second \citep{Liao_2022}, also focused on drug-naïve children with TS , assessed topological brain alterations. If they found some networks metrics as abnormal at the global level (i.e., increased global efficiency, decreased path length), they also showed some nodal changes, especially in the cortico-striato-thalamo-cortical circuit (i.e., supplementary motor area, caudate nucleus, thalamus, superior parietal gyrus, posterior cingulate cortex). This study is especially relevant since the authors used brain metrics which are rarely investigated. The third study focused on gyral abnormalities \citep{McCann_2022}. They identified that the youngest patients with TS (children) had an increased surface curvature in the frontal cortex (opercular and triangular parts of the inferior frontal cortex), while the oldest (adolescents) had an increased grey matter volume in the cerebellum, the precentral cortex and the primary motor cortex.
Another interesting work was published last year, using different statistical models to classify BOLD rs-fMRI of patients with TS and healthy controls \citep{Xin_2022}. The model which achieved the highest accuracy (multivariate non-linear model, 94% of accuracy, 96% of sensitivity and 92% of specificity) was especially based on changes observed in the frontal cortex (superior, medial and middle frontal gyrus, supplementary motor area, pre- and postcentral cortex), basal ganglia (putamen, thalamus and caudate nucleus) and the cerebellum. In the future, this kind of work could lead to the build some specific tools to contribute to the diagnosis of TS.
From a more cognitive viewpoint, three studies linked specific TS symptoms to brain alterations. The first one investigated the relation between the structural connectivity of several basal ganglia (caudate nucleus, putamen, nucleus accumbens, subthalamic nucleus and the medial subthalamic region) and the cortex with anxiety and impulsivity in TS \citep{Temiz_2022}. They found a hyperconnectivity in TS patients between the left medial subthalamic region and the insula, entorhinal and temporal cortex. Moreover, the connectivity between the subthalamic nucleus and the left insula was shown as positively related to impulsivity and anxiety scores respectively measured with BIS-11 and the STAI. The second study focused on the role of GABA as related to the urges to tics through several measures of cortical inhibition obtained with TMS \cite{Larsh_2022}. The authors found that severe urges were negatively correlated to cortical excitability and long-interval cortical inhibition obtained in the primary motor cortex. However, they also found that more severe tics were positively correlated with both of these measures. Last, they found that the right supplementary motor area GABA (cortical excitability and long-interval cortical inhibition) was changed in TS patients compared to healthy controls. Altogether, they concluded that changes in the primary motor cortex were modulated by GABA within the supplementary motor area and could reflect compensatory mechanisms. The third study focused on the error-related negativity obtained with MEG \citep{Metzlaff_2022}. This measure is known to reflect processes of performance monitoring, to be increased during error processing and conflicting response, and to be related to the dopaminergic system and the prefrontal cortex activity. Based on a small sample of adults’ patients without any medication nor comorbidities (n=8) performing a Go-NoGo task, the authors showed a significant interaction between groups (TS vs. healthy controls) and response (correct vs. error). The authors explained this difference by suggesting that TS patients processed all their responses as erroneous, which means that TS patients had an altered performance monitoring.

Treatment

Psychological interventions

Behavior therapy (BT) is recommended as the first-line intervention for TS/CTD in treatment guidelines published by the American Academy of Neurology (AAN)\citep{Pringsheim_2019} and the European Society for the Study of Tourette Syndrome (ESSTS) \citep{M_ller_Vahl_2021}. Two types of BT are recommended, of which is Habit Reversal Training (HRT) and its extended package Comprehensive Behavioral Intervention for Tics (CBIT) has the strongest evidence base. The second recommended BT-intervention, Exposure and Response Prevention (ERP), has comparatively less support to date, but is especially popular among clinicians and researchers in Europe \citep{Andrén2022}
Remote delivery of BT has become increasingly popular within the last years as a way to make BT more accessible to healthcare seeking individuals with TS/CTD. Several new studies on remote delivery of BT were published in 2022. The by far largest study was conducted in Sweden by Andrén and colleagues \citep{Andrén2022a} where 221 young individuals were randomized to therapist-supported, internet-delivered ERP or therapist-supported, internet-delivered psychoeducation (comparator). The results showed that both groups improved on the primary outcome (tic severity as measured by the Yale Global Tic Severity Scale - Total Tic Severity Score [YGTSS-TTS]) from baseline to the primary endpoint (3 months post-treatment). YGTSS-TTS reductions were 6.1 points (27%) in the ERP group and 5.3 points (23%) in the comparator. Contrary to the similar ORBIT study conducted in the UK \citep{Hollis2021}, there was no significant interaction of group and time on the primary outcome. However, treatment response rates at the 3-month follow-up were identical in both studies, with significantly more treatment responders in ERP (47%) than in the comparator (29%). The authors concluded that both internet-delivered interventions may be efficacious for young individuals with TS/CTD. Long-term follow-up data will be published in a future publication.
Internet-delivered BT has also recently been evaluated in Israel. Originally published in 2020, Rachamim and colleagues compared internet-delivered CBIT to waitlist in a randomized controlled trial (RCT) of 41 youth with TS/CTD \citep{Rachamim2022}. The results showed that internet-delivered CBIT was feasible to implement and superior to waitlist. In a new analysis of the same data published in 2022 \citep{Rachamim2021}, the authors focused on 27 treatment completers with comorbid attention deficit hyperactivity disorder (ADHD; n=16) or comorbid obsessive-compulsive disorder (OCD; n=11). This new analysis showed that, like the complete sample, tic severity (YGTSS-TTS) improved in both the ADHD and the OCD groups, although the OCD group improved significantly less than participants without comorbid OCD.
Another way of delivering BT remotely is through videoconferencing, a format which increased in popularity worldwide during the COVID-19 pandemic. In an Italian RCT conducted by Prato and colleagues \citep{Prato2022} 40 youth with TS were randomized to BT (HRT or ERP) delivered face-to-face at a clinic or remotely via videoconference. Participants improved on the YGTSS-TTS in both groups, in line with previous studies \citep{Himle2012}\citep{Ricketts2016}. This did however not, contrary to the authors’ claim, indicate that the two interventions were to be considered as equally efficacious, since the study lacked a pre-defined non-inferiority aim. The videoconference format was also partly used in a naturalistic study of ERP conducted at a TS/CTD specialist clinic in Denmark. In this study by Sørensen and colleagues \citep{Soerensen2023}\citep{Soerensen2023a}, 116 youth received ERP (either face-to-face [n=72] or via videoconference [n=44]) and were followed up one-year post-treatment. The study showed significant short- and long-term tic severity reductions (YGTSS-TTS) in both groups, with no significant between-group differences. Participants who completed the planned ERP sessions or discontinued early due to a satisfactory tic reduction, improved significantly more than participants who dropped out due to lack of motivation. Firm conclusions are limited by the open design, but the study overall provides support for both face-to-face and videoconference delivery of ERP. 
Another way to make BT more accessible is the group format, where the simultaneous treatment of several individuals by one therapist may save therapist resources. Based in the Republic of Korea, Kang and colleagues \citep{Kang2022} conducted a non-randomized controlled study (n=30) comparing group-CBIT (n=18) to a supportive psychotherapy and psychoeducational control condition (n=12). Overall, the baseline TS/CTD severity of the sample was mild. The CBIT group showed modest improvements, with the clearest result being superiority over the comparator in reducing tic-related impairment. The study provided some preliminary support to the feasibility of providing CBIT in a group format in this Korean context. Also published in 2022, Inoue and colleagues \citep{Inoue2022} evaluated group-CBIT in a case series (n=3) in Japan. In this study, group-CBIT was delivered via videoconference software, to further increase accessibility of BT to individuals in the region. The results showed an average tic severity reduction (YGTSS-TTS) of 7 points from baseline to post-treatment. Overall, the treatment was concluded feasible, acceptable, and promising for further evaluation.
A few studies on face-to-face CBIT were also conducted in 2022. In a US study, Greenberg and colleagues \citep{Greenberg2023} evaluated a modified CBIT intervention, which also included the treatment of comorbid ADHD and associated psychosocial impairment (from both TS/CTD and ADHD). Seventeen young participants with both TS/CTD and ADHD were randomized to modified CBIT (n=9) or a traditional CBIT comparator (n=8). The results showed significant improvements in tic severity, tic-related impairment, and ADHD severity for both groups, but the study was likely underpowered to detect between-group differences. Overall, the results indicated feasibility and acceptability for this modified treatment for youth with TS/CTD and ADHD. In a Chinese RCT, Xu and colleagues  \citep{Xu2022} recruited 37 youth with TS/CTD to compare face-to-face CBIT (n=12), face-to-face CBIT combined with pharmacotherapy (n=10), and pharmacotherapy alone (n=15). Tic severity (YGTSS-TTS) improved for all three groups between baseline and post-treatment. Although the approach of comparing BT and pharmacotherapy is relatively novel for the TS/CTD field, the study lacked sufficient power for between-group comparisons.
Lastly, interest in investigating the underlying working mechanisms of BT has increased in later years. In a study of 80 adults with TS, Ramsey and colleagues \citep{Ramsey2022} used structural equation modeling (SEM) to examine the distress provoked by the PU in patients with tics. They concluded that higher levels of premonitory urge intolerance predicted greater levels of tic severity and tic-related impairment. This result highlights a potential clinical implication of targeting the concept of urge intolerance, rather than for instance urge severity, in BT. In an RCT including 53 youth, McGuire and colleagues \citep{McGuire2022} investigated the relationship between several pre-selected cognitive control processes and face-to-face CBIT outcomes. The results showed that only one of the investigated processes – baseline inhibition/switching (as measured by the D-KEFS Color Word Interference Test) – predicted post-treatment tic severity. Interestingly, Gur and colleagues \citep{Gur2022} studied cognitive inhibition and emotion regulation before and after CBIT group therapy. 55 participants aged 8-15 years with tic disorders were randomly assigned to the CBIT group or the Educational Intervention group and compared on tests of cognitive inhibition and emotion regulation strategies. Their results showed an increase in cognitive reappraisal in the-CBIT group only, which was associated with higher intellectual ability. This study raises the possibility that CBIT contributes beyond tic control to cognitive and emotional regulation.