Recent Submissions

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

    Jackson, Georgina M.; Jackson, Stephen R. (2021)
    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.
  • Efficacy and cost-effectiveness of therapist-guided internet-delivered behaviour therapy for children and adolescents with Tourette syndrome: study protocol for a single-blind randomised controlled trial

    Hall, Charlotte L.; Davies, E. Bethan; Hollis, Chris P. (2021)
    BACKGROUNDTreatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial's primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention.METHODSIn this single-blind superiority RCT, 220 participants (9-17 years) with TS/CTD throughout Sweden will be randomised to 10-12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale - Total Tic Severity Score. Treatment response is operationalised as scores of "Very much improved" or "Much improved" on the Clinical Global Impression - Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses.DISCUSSIONParticipant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint.TRIAL REGISTRATIONClinicalTrials.gov NCT03916055 . Registered on 16 April 2019.
  • Therapist-supported online remote behavioural intervention for tics in children and adolescents in England (ORBIT): a multicentre, parallel group, single-blind, randomised controlled trial

    Hollis, Chris P.; Hall, Charlotte L.; Brown, Beverley J.; Chamberlain, Liam R.; Davies, E. Bethan; McKenzie, Caitlin; Khan, Kareem; Kilgariff, Joseph; Glazebrook, Cris (2021)
    Background: Exposure and Response Prevention (ERP) for tics appears a promising form of behaviour therapy for online delivery which could widen access to treatment. However, the effectiveness of ERP in general, and in particular when delivered online, remains uncertain. We evaluated the effectiveness of internet-delivered, therapist-supported and parent-assisted ERP for tics. Methods: Multi-centre, parallel group, single-blind, randomised controlled trial. Eligible participants were aged 9-17 years with Tourette syndrome/chronic tic disorder, who had not received behaviour therapy for tics within 12 months, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of >15, or >10 if motor or vocal tics only. Participants were recruited via 16 patient identification centres, two study sites in England (Nottingham and London), or online self-referral, and were randomised (1:1) by blinded outcome-assessors to receive either 10 weeks of ERP or psychoeducation (active control). The primary outcome was YGTSS-TTSS at 3 months’ post-randomisation, analysis was by intention-to-treat. The mean cost per patient for the intervention were calculated. Longer term follow-ups are still on-going. Registrations are ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). Findings: Between 8th May 2018 and 30th September 2019, 224 participants were enrolled; 112 to ERP and 112 to psychoeducation. The sample was predominately male (177; 79%) and of white ethnicity (195; 87%). The difference between the groups on the YGTSS-TTSS was -2.29 points (95% CI: -3.86 to -0.71), a reduction favouring the ERP intervention at 3 months, an effect that increased by 6 months post-randomisation (-2.64, 95% CI: -4.56 to -0.73). The average therapist time spent supporting the intervention was 2.5 hours. The additional cost per participant of the ERP intervention compared to psychoeducation was £159 (95% CI -£53 to £370). There were two unrelated serious adverse events, both in the psychoeducation group. Interpretation: ERP is an effective behavioural therapy for tics. Digitally enabled ERP with minimal therapist contact time represents an efficient public mental health approach to improve access to behavioural therapy for tics in children and adolescents.
  • Fidelity of delivery and contextual factors influencing children's level of engagement: Process evaluation of the online remote behavioral intervention for tics trial

    Khan, Kareem; Hollis, Chris P.; Hall, Charlotte L.; Davies, E. Bethan; Glazebrook, Cris (2021)
    Background: The Online Remote Behavioral Intervention for Tics (ORBIT) study was a multicenter randomized controlled trial of a complex intervention that consisted of a web-based behavioral intervention for children and young people with tic disorders. In the first part of a two-stage process evaluation, we conducted a mixed methods study exploring the reach, dose, and fidelity of the intervention and contextual factors influencing engagement. Objective: This study aims to explore the fidelity of delivery and contextual factors underpinning the ORBIT trial. Methods: Baseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (N=112). The experiences of being in the intervention were explored through semistructured interviews with children (n=20) and parent participants (n=20), therapists (n=4), and referring clinicians (n=6). A principal component analysis was used to create a comprehensive, composite measure of children and young people’s engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices, including chapters accessed, number of pages visited, and number of log-ins. The engagement factor score was used as the dependent variable in a multiple linear regression analysis with various contextual variables as independent variables to assess if there were any significant predictors of engagement. Results: The intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. The engagement was high, with child participants completing an average of 7.5 of 10 (SD 2.7) chapters, and 88.4% (99/112) of participants completed the minimum of the first four chapters—the predefined threshold effective dose. Compared with the total population of children with tic disorders, participants in the sample tended to have more educated parents and lived in more economically advantaged areas; however, socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site versus the Nottingham site (P=.01), self-referred versus clinic referred (P=.04), higher parental engagement as evidenced by the number of parental chapters completed (n=111; ρ=0.73; P<.001), and more therapist time for parents (n=111; ρ=0.46; P<.001). A multiple linear regression indicated that parents’ chapter completion (β=.69; t110=10.18; P<.001) and therapist time for parents (β=.19; t110=2.95; P=.004) were the only significant independent predictors of child engagement factor scores. Conclusions: Overall, the intervention had high fidelity of delivery and was evaluated positively by participants, although reach may have been constrained by the nature of the randomized controlled trial. Parental engagement and therapist time for parents were strong predictors of intervention implementation, which has important implications for designing and implementing digital therapeutic interventions in child and adolescent mental health services.
  • The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome

    Jackson, Stephen R.; Jackson, Georgina M. (2021)
    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.
  • Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

    Jackson, Georgina M.; Jackson, Stephen R. (2021)
    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.
  • Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people

    Hall, Charlotte L.; Brown, Beverley J.; Chamberlain, Liam R.; Davies, E. Bethan; Khan, Kareem; McKenzie, Caitlin; Hollis, Chris P. (2020)
    BACKGROUNDDespite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT).METHODWe extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online.RESULTSData were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials.CONCLUSIONAn approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery.TRIAL REGISTRATIONThe ORBIT trial is registered with ISRTCN ( ISRCTN70758207 ) Registered on March 20, 2018. and ClinicalTrials.gov ( NCT03483493 ). Registered on March 30, 2018.
  • Using online support communities for Tourette syndrome and tic disorders: Online survey of users' experiences

    Davies, E. Bethan (2020)
    BACKGROUNDPeople living with a tic disorder (TD)-such as Tourette syndrome (TS)-experience many negative psychological and social challenges arising from chronic tics, such as stigmatization from peers and poorer quality of life, and these can impact upon their families too. It can be difficult for this population to access face-to-face support for tics, and so online support communities offer one avenue for support from peers facing similar experiences. However, little is known about how online support communities may be used by people with TS and other TDs, and by others (eg, parents, caregivers) supporting a person with TS/TD.OBJECTIVEThis study aimed to explore users' experiences of participation in online support communities for TS and TDs.METHODSIn total, 90 respondents (aged 13-62 years; 62% [56/90] female) from 13 countries completed an online survey exploring their experiences of using online support communities for TS and TDs. Respondents were people living with TS/TD themselves (n=68) or supportive others of someone with TS/TD (eg, parent, sibling, spouse; n=14), or both (n=8). The online survey contained open-ended questions eliciting their self-reported motivations for using online communities, their benefits and drawbacks of participation, and whether online support communities affected offline management of tics. Responses were analyzed using thematic analysis.RESULTSSeven overarching themes captured experiences of using online support communities for TS/TDs. The overwhelming reason for their use was to find accessible support due to a lack of offline face-to-face support. Online support communities were valued sources of informational and emotional support, and also had a positive impact upon helping users' psychological well-being. Online communities helped provide a space where people with TS/TDs could feel accepted and reduce the social isolation they felt offline. The suggestible nature of tics and being reminded of the challenging nature of TDs were main disadvantages arising from using online support communities, alongside conflict arising within online communities.CONCLUSIONSThe findings suggest that online support communities appear to offer valuable informational and emotional support to those living with TS/TD and their families too, especially given the lack of locally available support. This facilitates a sense of community online, which can help users in overcoming long-standing social isolation and aid self-reported improvements in psychosocial well-being. Users reported some drawbacks in engaging with online support communities, such as conflict between different types of users and triggering content, which negatively affected experiences of community participation.
  • Therapist-supported online interventions for children and young people with tic disorders: Lessons learned from a randomized controlled trial and considerations for future practice

    Chamberlain, Liam R.; Hall, Charlotte L.; Davies, E. Bethan; Kilgariff, Joseph; Hollis, Chris P. (2020)
    In recent years, research into internet-based cognitive behavioral therapy (iCBT) has suggested that therapist-guided digital interventions have greater engagement, adherence, and effectiveness than self-directed digital therapies. While research has focused on the effectiveness of, and adherence to, these interventions, less attention has been paid to their implementation in practice and what aspects of the therapist role support success. An understanding of the key factors related to the therapist role and intervention delivery is required if these iCBTs are to be applied in routine clinical care and outcomes optimized. In light of the coronavirus disease 2019 (COVID-19) pandemic, there is greater emphasis on allowing patients access to remote therapies. We report the experiences and reflections of 4 therapists and their 2 supervisors in delivering an online, therapist-supported intervention in a randomized controlled trial for children and young people with tic disorders (the Online Remote Behavioural Intervention for Tics [ORBIT] trial). Themes discussed include the importance of training, supervision, creating support documents/manuals, and record keeping. Alongside this are communication strategies used by therapists to encourage patient adherence and treatment effectiveness. These include rapport building, treatment personalization, and suggestions for overcoming non-engagement. These reflections offer important considerations for the delivery of iCBTs as well as implications associated with the implementation of these interventions in existing services and future research studies. We share thoughts on where iCBTs may sit in a stepped care model, how services may deal with comorbid conditions, and the potential role of iCBTs in collecting clinical data.
  • Developing the Premonitory Urges for Tic Disorders Scale-Revised (PUTS-R)

    Jackson, Georgina M.; Jackson, Stephen R. (2020)
    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

    Jackson, Stephen R.; Kim, Soyoung; Jackson, Georgina M. (2020)
    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.
  • Entraining movement-related brain oscillations to suppress tics in Tourette syndrome

    Dyke, Katherine; Jackson, Georgina M.; Jackson, Stephen R. (2020)
    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.
  • The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome

    Jackson, Stephen R.; Jackson, Georgina M. (2020)
    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.
  • Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome

    Jackson, Stephen R.; Jackson, Georgina M. (2020)
    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.
  • Rethinking the nature of inhibitory control deficits in Tourette syndrome

    Jackson, Georgina M. (2020)
    This scientific commentary refers to ‘Impaired automatic but intact volitional inhibition in primary tic disorders’, by Rawji etal. (doi:10.1093/brain/awaa024).
  • Protocol for the Process Evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) randomized controlled trial for children and young people

    Khan, Kareem; Hollis, Chris P.; Hall, Charlotte L.; Davies, E. Bethan; Brown, Beverley J.; Glazebrook, Cris (2020)
    BACKGROUND: Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. METHODS: The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. DISCUSSION: This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.
  • Reply: Forward model deficits and enhanced motor noise in Tourette syndrome?

    Jackson, Stephen R.; Kim, Soyoung; Dyke, Katherine; Jackson, Georgina M. (2019)
    This is a letter to the editor.
  • Effects of single-session cathodal transcranial direct current stimulation on tic symptoms in Tourette's syndrome

    Jackson, Georgina M.; Nixon, Elena; Jackson, Stephen R. (2019)
    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.
  • Impaired forward model updating in young adults with Tourette syndrome

    Kim, Soyoung; Jackson, Georgina M.; Dyke, Katherine; Jackson, Stephen R. (2019)
    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.
  • Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents - 'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial

    Hall, Charlotte L.; Davies, E. Bethan; Brown, Susan S.; Craven, Michael P.; Glazebrook, Cris (2019)
    INTRODUCTION: Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms. METHODS AND ANALYSIS: This parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9-17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02). ETHICS AND DISSEMINATION: The findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079). TRIAL REGISTRATION NUMBERS: ISRCTN70758207 and NCT03483493; Pre-results.

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