A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) are neurological disorders of childhood onset characterized by the occurrence of tics; repetitive, purposeless, movements or vocalizations of short duration which can occur many times throughout a day. Currently, effective treatment for tic disorders is an area of considerable unmet clinical need. We aimed to evaluate the efficacy of a home-administered neuromodulation treatment for tics involving the delivery of rhythmic pulse trains of median nerve stimulation (MNS) delivered via a wearable 'watch-like' device worn at the wrist. We conducted a UK-wide parallel double-blind sham-controlled trial for the reduction of tics in individuals with tic disorder. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve for a pre-determined duration each day, and was intended to be used by each participant in their home once each day, 5 days each week, for a period of 4 weeks. Between 18th March 2022 and 26th September 2022, 135 participants (45 per group) were initially allocated, using stratified randomization, to one of the following groups; active stimulation; sham stimulation or to a waitlist (i.e. treatment as usual) control group. Recruited participants were individuals with confirmed or suspected TS/CTD aged 12 years of age or upward with moderate to severe tics. Researchers involved in the collection or processing of measurement outcomes and assessing the outcomes, as well as participants in the active and sham groups and their legal guardians were all blind to the group allocation. The primary outcome measure used to assess the 'offline' or treatment effect of stimulation was the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS) assessed at the conclusion of 4 weeks of stimulation. The primary outcome measure used to assess the 'online' effects of stimulation was tic frequency, measured as the number of tics per minute (TPM) observed, based upon blind analysis of daily video recordings obtained while stimulation was delivered. The results demonstrated that after 4-week stimulation, tic severity (YGTSS-TTSS) had reduced by 7.1 points (35 percentile reduction) for the active stimulation group compared to 2.13/2.11 points for the sham stimulation and waitlist control groups. The reduction in YGTSS-TTSS for the active stimulation group was substantially larger, clinically meaningful (effect size = .5) and statistically significant (p = .02) compared to both the sham stimulation and waitlist control groups, which did not differ from one another (effect size = -.03). Furthermore, blind analyses of video recordings demonstrated that tic frequency (tics per minute) reduced substantially (-15.6 TPM) during active stimulation compared to sham stimulation (-7.7 TPM). This difference represents a statistically significant (p < .03) and clinically meaningful reduction in tic frequency (>25 percentile reduction: effect size = .3). These findings indicate that home-administered rhythmic MNS delivered through a wearable wrist-worn device has the potential to be an effective community-based treatment for tic disorders.

Self-help Digital Interventions Targeted at Improving Psychological Well-being in Young People With Perceived or Clinically Diagnosed Reduced Well-being: Systematic Review.

BACKGROUND: Levels of well-being are declining, whereas rates of mental health problems remain high in young people. The World Health Organization defines mental health as not merely the absence of mental disorder but also includes social and psychological well-being as integral to positive mental health, highlighting that mental health is applicable to young people with mental health conditions and those without a diagnosis of a mental health condition. Reduced mental well-being have been identified in studies of young people with clinical populations, as well as in populations consisting of nonclinical young people. Self-help digital interventions can be delivered at mass at a low cost and without the need for trained input, thereby facilitating access to support for well-being. Self-help interventions are effective in young people with mental health conditions, but systematic reviews of such studies have been limited to randomized controlled trials, have not included reduced well-being as an inclusion criterion, and do not consider engagement factors such as retention. OBJECTIVE: The objective of this study was to systematically review all controlled studies of digitally delivered, self-administered interventions for young people aged 9 to 25 years, with perceived or clinically diagnosed reduced psychological well-being. Participant retention and effectiveness of the interventions were also explored. METHODS: A systematic search of the PsycInfo, EMBASE, Cochrane, Scopus, and MEDLINE databases from inception to 2021, reference searches of relevant papers, and gray literature was carried out for digitally controlled studies conducted with young people with perceived or clinically diagnosed reduced well-being, aimed at improving psychological well-being. Data were extracted to identify the effectiveness and retention rates of the interventions and the quality of the studies. RESULTS: Overall, 1.04% (12/1153) of studies met the inclusion criteria: 83% (10/12) of studies were randomized controlled trials and 17% (2/12) were controlled pre-post studies. Most (6/12, 50%) studies aimed to improve symptoms of depression; 3 interventions aimed at both anxiety and depressive symptoms and 2 studies aimed at improving social functioning difficulties. Owing to the high risk of bias across interventions and lack of similar outcome measures, a meta-analysis was not conducted. Retention rates across studies were regarded as good, with moderate to high retention. Overall, the findings indicated that predominantly self-administered self-help interventions improved well-being in the areas targeted by the intervention and identified additional areas of well-being that were positively affected by interventions. Few interventions supported psychological well-being that was different from those used by young people with a clinical diagnosis of mental illness or young people from neurodiverse backgrounds. CONCLUSIONS: The findings, along with the advantages of self-help interventions, highlight the need for upscaling self-help interventions to better support vulnerable populations of young people who experience poor psychological well-being. TRIAL REGISTRATION: PROSPERO CRD42019129321; https://tinyurl.com/4fb2t4fz.

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit dysfunction and hyper-excitability of cortical limbic and motor regions that lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as an urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued by some that tics should be viewed as voluntary movements that are executed in response to the presence of PU. To investigate this issue further, we conducted a study using electroencephalography (EEG). We recorded movement-related EEG (mu- and beta-band oscillations) during (1) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (2) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta oscillations are not reliably observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, the basal ganglia and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.

Non-invasive brain stimulation as therapy: systematic review and recommendations with a focus on the treatment of Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental condition characterised by tics, which are stereotyped movements and/or vocalisations. Tics often cause difficulties in daily life and many with TS express a desire to reduce and/or gain control over them. No singular effective treatment exists for TS, and while pharmacological and behavioural interventions can be effective, the results are variable, and issues relating to access, availability and side effects can be barriers to treatment. Consequently, over the past decade, there has been increasing interest into the potential benefits of non-invasive brain stimulation (NIBS) approaches. This systematic review highlights work exploring NIBS as a potential treatment for TS. On balance, the results tentatively suggest that multiple sessions of stimulation applied over the supplementary motor area (SMA) may help to reduce tics. However, a number of methodological and theoretical issues limit the strength of this conclusion, with the most problematic being the lack of large-scale sham-controlled studies. In this review, methodological and theoretical issues are discussed, unanswered questions highlighted and suggestions for future work put forward.

The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by 'premonitory sensory/urge phenomena' (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in 'urges-for-action' more generally. In the current study, we utilized voxel-based morphometry (VBM) techniques, together with 'seed-to-voxel' structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid-cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior cingulate 'seed' regions demonstrated that TS is associated with increased structural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.

Developing the Premonitory Urges for Tic Disorders Scale-Revised (PUTS-R).

BACKGROUND: Patients with Gilles de la Tourette syndrome (GTS) or chronic tic disorders frequently experience premonitory urges prior to tics. The 'Premonitory Urges for Tic Disorders Scale' (PUTS) is commonly used in order to assess urge severity in patients with tics. Several studies suggest that the PUTS might measure more than one dimension of urges. These include the quality and severity of premonitory urges. METHODS: This study aims to replicate and extend previous findings concerning the psychometric properties of the PUTS and its underlying dimensions in a large sample of 241 patients with GTS including both adults (n = 93; mean age = 34.2 ± 12.84; 73 male) and minors (n = 148; mean age = 11.8 ± 2.86; 123 male), pooled from three different recruitment sites. RESULTS: Data analysis confirmed good reliability across the PUTS items for both minors and adults and acceptable item characteristics for items 2-8. A factor analysis of items 1-8 confirmed the existence of two factors in both age groups. CONCLUSIONS: The results suggest that the PUTS might benefit from several further small modifications, such as rephrasing items 1 and 9 to increase convergence with the overall construct of the scale. Finally, we propose a revised version of the PUTS, consisting of two subscales: one for urge severity and another one for urge quality by including several new items.

A feasibility study for somatomotor cortical mapping in Tourette syndrome using neuronavigated transcranial magnetic stimulation.

Tourette syndrome (TS) is a hyperkinetic movement disorder characterised by the occurrence of chronic motor and vocal tics, and is associated with alterations in the balance of excitatory and inhibitory signalling within key brain networks; in particular the cortical-striatal-thalamic-cortical (CSTC) brain circuits that are implicated in movement selection and habit learning. Converging evidence indicates abnormal brain network function in TS may be largely due to the impaired operation of GABA signalling within the striatum and within cortical motor areas, leading to the occurrence of tics. TS has been linked to a heightened sensitivity to somatic stimulation and altered processing of somatosensory information, and there is evidence to indicate that alterations in GABAergic function is likely to contribute to altered somatomotor function. Based upon this evidence, we hypothesised that the specificity of somatomotor representations in primary motor cortex would likely be reduced in individuals with TS. To test this, we used a rapid acquisition method together with neuronavigated transcranial magnetic stimulation (nTMS) to measure the cortical representation of a several different muscles in a group of young adults with TS and a matched group of typically developing individuals.

Tic frequency and behavioural measures of cognitive control are improved in individuals with Tourette syndrome by aerobic exercise training.

Previous observations of improvements in cognition in typically developing children following moderate to vigorous exercise (e.g., Budde, Voelcker-Rehage, Pietrabyk-Kendziorra, Ribeiro, & Tidow, 2008; Hillman et al., 2009) have led to increased interest in the potential benefits of exercise for children with neurodevelopmental disorders, involving difficulties in self-regulation (e.g., Halperin & Healey, 2011; Archer & Kostrzewa, 2012). Using a within-sample design, the current study looked at the beneficial effects of non-aerobic movement training (Tai Chi), compared to aerobic movement training (Kick Boxing), on behavioural measures of cognitive control and clinical measures of tic severity in a group of young people with Tourette Syndrome (TS). We demonstrate that Kick Boxing, but not Tai Chi, led to a significant enhancement in cognitive control task performance. Furthermore, while tic frequency (tics per minute) was reduced during both types of exercise, this reduction was significantly greater, and sustained for longer, following Kick Boxing. Importantly, the magnitude of the increase in cognitive control following Kick Boxing predicted the degree of reduction in tic frequency. These findings suggest that aerobic exercise may be a useful intervention for improving self-regulation of tics in young people with TS, probably through enhancements in associated cognitive control circuits.

Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the occurrence of vocal and motor tics. Tics are involuntary, repetitive movements and vocalizations that occur in bouts, typically many times in a single day, and are often preceded by a strong urge-to-tic-referred to as a premonitory urge (PU). TS is associated with the following: dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits implicated in the selection of movements, impaired operation of GABA signaling within the striatum, and hyper-excitability of cortical sensorimotor regions that might contribute to the occurrence of tics. Non-invasive brain stimulation delivered to cortical motor areas can modulate cortical motor excitability, entrain brain oscillations, and reduce tics in TS. However, these techniques are not optimal for treatment outside of the clinic. We investigated whether rhythmic pulses of median nerve stimulation (MNS) could entrain brain oscillations linked to the suppression of movement and influence the initiation of tics in TS. We demonstrate that pulse trains of rhythmic MNS, delivered at 12 Hz, entrain sensorimotor mu-band oscillations, whereas pulse trains of arrhythmic MNS do not. Furthermore, we demonstrate that although rhythmic mu stimulation has statistically significant but small effects on the initiation of volitional movements and no discernable effect on performance of an attentionally demanding cognitive task, it nonetheless leads to a large reduction in tic frequency and tic intensity in individuals with TS. This approach has considerable potential, in our view, to be developed into a therapeutic device suitable for use outside of the clinic to suppress tics and PU in TS.

Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neurological disorder characterised by the occurrence of motor and vocal tics and the presence of premonitory sensory/urge phenomena. Functional neuroimaging studies in humans, and experimental investigations in animals, have shown that the genesis of tics in TS involve a complex interaction between cortical-striatal-thalamic-cortical brain circuits and additionally appears to involve the cerebellum. Furthermore, structural brain imaging studies have demonstrated alterations in grey matter (GM) volume in TS across a wide range of brain areas, including alterations in GM volume within the cerebellum. Until now, no study to our knowledge has yet investigated how GM structural covariance networks linked to the cerebellum may be altered in individuals with TS. In this study we employed voxel-based morphometry, and a 'seed-to-voxel' structural covariance network (SCN) mapping approach, to investigate alterations in GM cerebellar volume in people with TS, and alterations in cerebellar SCNs associated with TS. Data from 64 young participants was entered in the final analysis, of which 28 had TS while 36 were age-and sex-matched healthy volunteers. Using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) atlas, we found reduced GM volume in cerebellar lobule involved in higher-order cognitive functions and sensorimotor processing, in patients. In addition, we found that several areas located in frontal and cingulate cortices and sensorimotor network in addition to subcortical areas show altered structural covariance with our cerebellar seed compared to age-matched controls. These results add to the increasing evidence that cortico-basal ganglia-cerebellar interactions play an important role in tic symptomology.

The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by 'premonitory sensory/urge phenomena' (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance, not least because they form the core component in many behavioural therapies used in the treatment of tic disorders. Several lines of evidence indicate that the insular cortex may play a particularly important role in the generation of PU in TS and 'urges-for-action' more generally. In the current study we utilised voxel-based morphometry techniques together with 'seed-to-voxel' structural covariance network (SCN) mapping to investigate the putative role played by the right insular cortex in the generation of motor tics and the experience of PU in a relatively large group of young people TS. We demonstrate that clinical measures of motor tic severity and PU are uncorrelated with one another, that motor tic severity and PU scores are associated with separate regions of the insular cortex, and that the insula is associated with different structural covariance networks in individuals with TS compared to a matched group of typically developing individuals.

Effects of single-session cathodal transcranial direct current stimulation on tic symptoms in Tourette's syndrome.

Tourette syndrome is a neurodevelopmental disorder characterised by motor and phonic tics. For some, tics can be managed using medication and/or forms of behavioural therapy; however, adverse side effects and access to specialist resources can be barriers to treatment. In this sham-controlled brain stimulation study, we investigated the effects of transcranial direct current stimulation (tDCS) on the occurrence of tics and motor cortical excitability in individuals aged 16-33 years with Tourette syndrome. Changes in tics were measured using video recordings scored using the RUSH method (Goetz et al. in Mov Disord 14:502-506, 1999) and changes in cortical excitability were measured using single-pulse transcranial magnetic stimulation (spTMS) over the primary motor cortex (M1). Video recordings and spTMS measures were taken before and after 20 min of sham or active tDCS: during which cathodal current was delivered to an electrode placed above the supplementary motor area (SMA). Tic impairment scores, calculated from the video data, were significantly lower post-cathodal stimulation in comparison with post-sham stimulation; however, the interaction between time (pre/post) and stimulation (cathodal/sham) was not significant. There was no indication of a statistically significant change in M1 cortical excitability following SMA stimulation. This study presents tentative evidence that tDCS may be helpful in reducing tics for some individuals, and provides a foundation for larger scale explorations of the use of tDCS as a treatment for reducing tics.

Implicit sequence learning in young people with Tourette syndrome with and without co-occurring attention-deficit/hyperactivity disorder.

Impaired habit-learning has been proposed to underlie the tic symptoms of Tourette syndrome (TS). However, accounts differ in terms of how habit-learning is altered in TS, with some authors proposing habit formation is impaired due to a deficient 'chunking' mechanism, and others proposing habit-learning is overactive and tics reflect hyperlearned behaviours. Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with TS and is known to affect cognitive function in young people with co-occurring TS and ADHD (TS + ADHD). It is unclear, however, how co-occurring ADHD symptoms affect habit-learning in TS. In this study, we investigated whether young people with TS would show deficient or hyperactive habit-learning, and assessed the effects of co-occurring ADHD symptoms on habit-learning in TS. Participants aged 9-17 years with TS (n = 18), TS + ADHD (n = 17), ADHD (n = 13), and typical development (n = 20) completed a motor sequence learning task to assess habit-learning. We used a 2 (TS-yes, TS-no) × 2 (ADHD-yes, ADHD-no) factorial analysis to test the effects of TS, ADHD, and their interaction on accuracy and reaction time indices of sequence learning. TS was associated with intact sequence learning, but a tendency for difficulty transitioning from sequenced to non-sequenced performance was suggestive of hyper-learning. ADHD was associated with significantly poorer accuracy during acquisition of the sequence, indicative of impaired habit-learning. There were no interactions between the TS and ADHD factors, indicating young people with TS + ADHD showed both TS- and ADHD-related atypicalities in habit-learning.

Impaired forward model updating in young adults with Tourette syndrome.

Current theories of motor control emphasize how the brain may use internal models of the body to ensure accurate planning and control of movements. One such internal model-a forward model-is thought to generate an estimate of the next motor state and/or the sensory consequences of an upcoming movement, thereby allowing movement errors to be monitored. In addition, forward models may provide a means by which to determine a sense of agency, i.e. the (conscious) sense of authorship and control over our actions. Tourette syndrome is a developmental neurological condition characterized by the occurrence of motor and phonic tics. The involuntary (or voluntary) nature of tics has been the subject of considerable debate, and it was recently argued that the presence of tics in Tourette syndrome could result in a blurring of any subjective boundary between voluntary and involuntary movements. In particular, it was proposed that the level of sensorimotor noise that accompanies tics may be particularly high in Tourette syndrome, and this may contribute to less efficient forward models used to determine agency. We investigated whether the internal monitoring of movements is impaired in individuals with Tourette syndrome, relative to a matched group of typically developing individuals, using a task that involved executing double-step aiming movements using a hand-held robot manipulandum. Participants were required on each trial to execute two movements in turn, each directed to a remembered target location without visual feedback. Importantly, we assumed that to perform accurately on the second (return) movement it would be necessary to update any forward model to take into account errors made during the first (outward) movement. Here we demonstrate that while the Tourette syndrome group were equally accurate, and no more variable, than the matched control group in executing aiming movements to the first (outward) target location, they were significantly less accurate, and exhibited greater movement variability, than controls when executing the second (return) movement. Furthermore, we show that for the return movement only, movement accuracy and movement variability were significantly predicted by the Tourette syndrome group's clinical severity scores. We interpret these findings as consistent with the view that individuals with Tourette syndrome may experience a reduction in the precision of the forward model estimates thought necessary for the accurate planning and control of movements.

Desired Features of a Digital Technology Tool for Self-Management of Well-Being in a Nonclinical Sample of Young People: Qualitative Study.

BACKGROUND: Adaptive coping behaviors can improve well-being for young people experiencing life stressors, while maladaptive coping can increase vulnerability to mental health problems in youth and into adulthood. Young people could potentially benefit from the use of digital technology tools to enhance their coping skills and overcome barriers in help-seeking behaviors. However, little is known about the desired digital technology use for self-management of well-being among young people in the general population. OBJECTIVE: This is a small, qualitative study aimed at exploring what young people desire from digital technology tools for the self-management of their well-being. METHODS: Young people aged 12-18 years were recruited from the general community to take part in semistructured interviews. Recorded data from the interviews were transcribed and analyzed using inductive thematic analysis. RESULTS: In total, 14 participants were recruited and completed the study, with a mean age of 14.6 years (female n=3). None of the participants reported using any digital tools specifically designed to manage well-being. However, as indicated through the emerged themes, young people used digital technology to reduce their stress levels and manage their mood, mainly through games, music, and videos. Overall, identified themes showed that young people were keen on using such tools and desired certain facets and features of an ideal tool for self-management of well-being. Themes related to these facets indicated what young people felt a tool should do to improve well-being, including being immersed in a stress-free environment, being uplifting, and that such a tool would direct them to resources based on their needs. The feature-based themes suggested that young people wanted the tool to be flexible and enable engagement with others while also being sensitive to privacy. CONCLUSIONS: The young people interviewed in this study did not report engaging with digital technology specialized to improving well-being but instead used media already accessed in their daily lives in order to self-manage their psychological states. As a result, the variety of coping strategies reported and digital tools used was limited to the resources that were already being used for recreational and social purposes. These findings contribute to the scarce research into young people's preferred use of digital technology tools for the self-management of their well-being. However, this was a small-scale study and the current participant sample is not representative of the general youth population. Therefore, the results are only tentative and warrant further investigation.

Visuomotor learning and unlearning in children and adolescents with tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neurological condition characterised by an evolving repertoire of chronic motor tics and one or more phonic tics. Tics, like habits, are inflexible and repetitive behaviours that are acquired over a period of time. It has been proposed that tics arise in TS as a result of increased habit learning: which may bias the child to acquire automatic behaviours (i.e., tics) more readily than is normal and make it harder to unlearn maladaptive habits once they have been acquired. Using a well-established visuomotor adaptation task, we investigated motor learning in a group of children and adolescents with a clinical diagnosis of TS relative to a group of age and gender matched typically developing individuals. In particular, we quantified differences in the strength and quality of motor learning and unlearning in TS, and the consolidation of motor learning over a 24 h washout period. We demonstrated that there was a marginally significant decrease in learning rate in the individuals with TS relative to age and gender matched typically developing controls. However, this effect was not associated with tic severity and could be entirely accounted for by the severity of co-occurring ADHD symptoms. Thus, once ADHD symptoms had been accounted for, there were no between group differences in learning rate or the degree of learning observed. By contrast, and more importantly, we found that following learning the rate of forgetting (unlearning) was significantly negatively associated with motor tic severity, such that individuals with more severe tics took longer to unlearn previously learnt motor patterns of behaviour. This finding is consistent with the proposal that TS is associated with alterations in the striatal habit learning system and with the view that TS may make it harder to unlearn maladaptive motor habits once they have been acquired.

Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography.

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by repetitive and intermittent motor and vocal tics. TS is thought to reflect fronto-striatal dysfunction and the aetiology of the disorder has been linked to widespread alterations in the functional and structural integrity of the brain. The aim of this study was to assess white matter (WM) abnormalities in a large sample of young patients with TS in comparison to a sample of matched typically developing control individuals (CS) using diffusion MRI. The study included 35 patients with TS (3 females; mean age: 14.0 ± 3.3) and 35 CS (3 females; mean age: 13.9 ± 3.3). Diffusion MRI data was analysed using tract-based spatial statistics (TBSS) and probabilistic tractography. Patients with TS demonstrated both marked and widespread decreases in axial diffusivity (AD) together with altered WM connectivity. Moreover, we showed that tic severity and the frequency of premonitory urges (PU) were associated with increased connectivity between primary motor cortex (M1) and the caudate nuclei, and increased information transfer between M1 and the insula, respectively. This is to our knowledge the first study to employ both TBSS and probabilistic tractography in a sample of young patients with TS. Our results contribute to the limited existing literature demonstrating altered connectivity in TS and confirm previous results suggesting in particular, that altered insular function contributes to increased frequency of PU.