DOI

Etiology

Genetics and epigenetics

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A risk model based on 10 genes with variants previously associated with tic disorders, tuned to allele frequencies relevant to the local population, produced an ROC curve for distinguishing TS from controls with area under the curve 0.62 \citep{Borczyk_2021}. This model was then applied to patients with other tic disorders, and the oligogenic risk score increased monotonically from tic-free people, to non-TS tic disorders, to TS patients as a group, to TS patients with severe symptoms. The polygenic signal from the Psychiatric Genomics Consortium (PGC) showed a similar increase across groups. The authors interpret the results as "evidence that typical and severe adult TS as well as other tic disorders may exist on a single spectrum in terms of their genetic background."

Environmental risk factors

\cite{Choi2023}  conducted a case-control study of prenatal and perinatal risk factors for the development of TS. Antiemetic exposure and medically assisted reproduction were found to increase the risk. 
According to a study by   \cite{Prato_2023}. reported that children and adolescents with TS who had COVID-19 infections may experience both short lasting as well as long lasting symptoms (long COVID). Of note, 35% of patients experienced worsening of tics and/or psychiatric comorbidities following a COVID-19 infection.   

Pathophysiology

Neurophysiology

In 2023, three studies assessed brain connectivity in individuals with TS using EEG. Jurgiel and colleagues investigated the additive and interactive effects of TS and ADHD on effective connectivity in children \citep{Jurgiel_2023}. They reported additive effects of aberrant effective connectivity in TS and ADHD spanning several frequency bands. Aberrant effective connectivity was mostly found in children with ADHD, who showed reduced effective connectivity across several posterior and occipital-frontal connections. TS was associated with increased connectivity from the left postcentral to the right precuneus and reduced connectivity from the left occipital cortex to the right precuneus. Another EEG study, which was conducted in adults, assessed functional connectivity within and across nodes of the default mode network \citep{Yang_2023}. They found increased beta-band connectivity between the left and right posterior cingulate/retrosplenial cortices, relative to controls. Also, using graph theoretical metrics, they found enhanced gamma-band degree centrality in the left temporal lobe, which was significantly correlated with increased tic severity. Finally, an EEG study specifically assessed functional connectivity during a tic suppression session in the context of a randomized controlled trial of CBIT \citep{Morand_Beaulieu_2023}. It was found that increased alpha-band functional connectivity during tic suppression predicted the reduction in phonic tics (but not motor tics) following CBIT.
Two EEG studies have investigated proactive control and binding processes in TS \citep{Wehmeyer_2023,Wendiggensen_2023}. In the first study, EEG markers of proactive control and binding were recorded during a cued task switching paradigm in adults with TS \citep{Wehmeyer_2023}. After temporal decomposition, they found an absence of N2 modulation but increased P3 for repeated responses on task switch trials in the C-cluster, which includes intermediate processes between stimulus and response. In the second study, a S1-S2 paradigm was used to assess binding processes in adolescents and adults with TS \citep{Wendiggensen_2023}. Their analyses, which focused on the theta frequency band, revealed that action file binding effects in the control group relied on the superior parietal regions cortex and the precuneus, whereas the superior frontal gyrus was involved in individuals with TS. Of note, both studies support the idea that integration of action in individuals with TS involves different neurophysiological processes, relative to controls.
To test whether altered social behaviors in TS reflected an overactive mirror neuron system, Weiblen and colleagues investigated mu suppression during an empathy for pain task in adults with TS \citep{Weiblen_2023}. Mu suppression is thought to reflect empathic abilities and could serve as a marker of mirror neuron system function. During the experimental task, participants viewed pictures of hand and feet in neutral or painful situations. Study results revealed that adults with TS showed reduced pain-related mu suppression relative to controls, suggesting altered processing of others’ emotional states.
Triggiani and colleagues assessed the sense of volition and the neural antecedents of tics and voluntary movements using a Libet's clock paradigm \citep{Triggiani_2023}. They asked adults with TS and controls to take note of the time they had the conscious intention to move and the time when they felt the initiation of a voluntary movement. However, groups did not differ on that matter. In those with TS, judgements of the timing of the intention and the initiation of tics were also noted, but those did not differ from the timing of voluntary movements. While most adults with TS showed a Bereitschaftspotential prior to tics, beta desynchronization was absent in a majority of individuals, suggesting dissociation between both processes. Furthermore, as commented by Gunduz and Ganos, the absence of beta desynchronization prior to tics could possibly help in distinguishing primary tics from functional tic-like behaviors  \citep{Gunduz_2023}.behaviors .
Other electrophysiological studies aimed to investigate motor cortical inhibition using transcranial magnetic stimulation. Consistent with previous findings \citep[see][]{Larsh_2022a}, Batschelett and colleagues found no difference between children with TS and controls in terms of motor cortex short-interval cortical inhibition \citep{Batschelett_2023a}. However, short-interval cortical inhibition was significantly associated with increased tic severity. Schmidgen and colleagues used transcranial magnetic stimulation to evoke the N100 event-related potential, a marker of motor cortical inhibition thought to reflect GABAB receptors functioning \citep{Schmidgen_2023}. They found reduced modulation of N100 by external (different stimulation intensities) and internal (different motor states: movement preparation and execution) modulation in children with TS. These results suggest altered modulation of motor cortical inhibition in TS, which would be related to GABAB processes.

Neuroimaging studies

One of the most noteworthy neuroimaging studies of the last year was conductedby Zouki et al. \citep{Zouki_2023}. Similar to a study published the preceding year \cite{Ganos_2022}, they combined both lesion-network mapping (derived from cases associated with tic-inducing lesions) and resting-state functional networks obtained in patients with TS. While the precise anatomical localization of the lesions did not reveal a singular site related to tics, the network-based analysis highlighted a neural network implicating the posterior putamen, the caudate nucleus, the globus pallidus externus, and the precuneus. As a second level analysis, this network was found the be functionally disconnected in TS patients with a specific cluster identified in the right frontal white matter and cingulate gyrus. As highlighted in a recent scientific commentary \cite{Ganos_2023}, the robustness of these findings underscores their potential translation into clinical practice, offering promising avenues for the development of targeted therapeutic interventions.