Dietary inflammatory index and its impact on severity and recurrence of Tourette syndrome in children.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and vocal tics, typically beginning in childhood. Despite significant research efforts, the exact pathophysiology of TS remains incompletely understood. Recent studies suggest that inflammation may play a role in the severity and progression of TS, pointing to the potential influence of dietary and lifestyle factors on the condition. Currently, research on the specific connection between dietary inflammatory index (DII) and TS is still in its early stages, requiring additional clinical and epidemiological studies to validate the strength and specific mechanisms of this connection. AIM: To investigate the association between DII and the severity, recurrence, and inflammatory levels of TS in children. METHODS: A total of 207 children diagnosed with TS in the pediatric department of Qingdao Chengyang People's Hospital from January 2022 to January 2023 were selected. They were divided into stable and unstable groups based on follow-up conditions. Before enrollment, general information of the children [age, gender, body mass index (BMI), guardian's education level, DII score, medical history, family history, academic stress, electronic device usage, medication, and disease progression] was assessed, and serum inflammatory levels were measured during follow-up visits. DII scores and Yale Global Tic Severity Scale (YGTSS) scores were calculated. Furthermore, based on YGTSS scores, the children were classified into mild, moderate, and severe groups. The DII, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels in each group were compared. RESULTS: Follow-up surveys were completed by 207 children and their guardians. Among them, 117 children were in the stable group, and 90 were in the recurrent group. We found no statistically significant differences in age, gender, comorbidities, BMI, and disease duration between the two groups (P > 0.05). However, academic stress, electronic device usage, medication, guardian's education level, and DII scores showed statistically significant differences between the groups (P < 0.05). Multifactorial regression analysis revealed that guardian's anxiety level, DII score, medication, academic stress, and family history were statistically significant factors (P < 0.05) affecting the recurrence of TS in children. Therefore, anxiety level, DII score, medication status, electronic device usage, and academic stress were identified as factors influencing the recurrence of TS in children. Among them, DII score, academic stress, and family history had odds ratios (OR) greater than 1, indicating risk factors, whereas medication status and guardian's education level had OR values less than 1, indicating protective factors. According to the YGTSS scores, children were categorized into mild, moderate, and severe groups. Comparative analysis of DII and inflammatory levels in children with different degrees of tic disorders revealed that the severe group had the highest DII and inflammatory levels, followed by the moderate group, and the mild group had the lowest levels. The trend of TS progression was consistent with the DII results. Receiver operating characteristic curves were plotted to predict disease progression in patients with TS via inflammatory markers. The areas under the curve for IL-6, CRP, and TNF-α were 0.894 (95%CI: 0.817-0.969), 0.793 (95%CI: 0.694-0.893), and 0.728 (95%CI: 0.614-0.843) respectively, with statistically significant differences (P < 0.05). According to the Youden index, the optimal cutoff values were IL-6 = 3.775 ng/L (sensitivity 68.1% and specificity 68.4%), CRP = 6.650 mg/L (sensitivity 60.6% and specificity 68.4%), and TNF-α = 0.666 (sensitivity 60.6% and specificity 71.1%). CONCLUSION: We found a certain correlation between DII and the severity, recurrence, and inflammatory levels of TS in children. Reasonable reduction in the intake of pro-inflammatory foods may be beneficial in reducing the risk of disease progression in children with TS.

An Observational Longitudinal Study on Seasonal Variations in Tourette Syndrome: Evidence for a Role of Ambient Temperature in Tic Exacerbation.

Tourette syndrome (TS) is a high-incidence neurobehavioral disorder that generally begins in childhood. Several factors play a role in its etiology, including genetic influence and auto-immune activation by streptococcal infections. In general, symptoms subside after the end of adolescence, but, in a significant number of patients, they remain in adulthood. In this study, we evaluated temporal variations in the two core clinical features of TS including tics and obsessive-compulsive disorder (OCD) symptoms. An observational longitudinal study lasting 15 months (2017-2019) was conducted on a cohort of 24 people recruited in Milan (Italy) who were diagnosed with a subtype of TS known as obsessive-compulsive tic disorder. Inclusion criteria included a global score of the Yale global tic severity scale (Y-GTSS) > 50, a Yale-Brown obsessive-compulsive scale (Y-BOCS) global score > 15, and TS onset at least one year prior. Y-GTSS and Y-BOCS data were acquired at six time points, together with local environmental data. Tics, but not OCD symptoms, were found to be more severe in spring and summer compared with winter and autumn (p < 0.001). Changes in tics displayed an appreciable oscillation pattern in the same subject and also a clear synchrony among different subjects, indicating an external orchestrating factor. Ambient temperature showed a significant correlation with Y-GTSS measurements (p < 0.001). We argue that the increase in tics observed during hot seasons can be related to increasing ambient temperature. We believe that our results can shed light on the seasonal dynamics of TS symptomatology and provide clues for preventing their worsening over the year.

Efficacy of cognitive-behavioral therapy combined with habit reversal training on anxiety disorders in children with Tourette's syndrome.

BACKGROUND: Cognitive-behavioral therapy (CBT) and habit reversal training (HRT) have shown application potential in addressing tic symptoms and comorbid psychiatric conditions. Despite their theoretical potential, empirical evidence on their combined efficacy remains limited. AIM: To evaluate the efficacy of CBT combined with HRT on anxiety disorders in children with Tourette's syndrome (TS). METHODS: Clinical data of children with TS admitted to our hospital from January 2022 to June 2023 were collected, and the patients were grouped into the conventional therapy (control) group and the CBT combined with HRT group. Baseline characteristics, anxiety scores, tic severity scores, treatment adherence, and parental satisfaction were assessed. Statistical analysis was performed using t-tests, chi-square tests, and correlation analysis. RESULTS: A total of 136 patients, including 65 patients in the control group and 71 patients in the CBT combined with HRT group, were included. The CBT combined with HRT group showed remarkable improvements compared with the control group. Post-intervention assessment revealed a decrease in anxiety scores from 63.52 ± 1.81 to 40.53 ± 1.64 (t = 2.022, P = 0.045), and the Yale Global Tic Severity Scale total score decreased from 22.14 ± 5.67 to 16.28 ± 4.91 (t = 2.288, P = 0.024). Treatment adherence was significantly higher in the CBT combined with HRT group (85.47 ± 7.62%) compared with the control group (82.32 ± 6.54%; t = 2.596, P = 0.010). Parental satisfaction scores were also higher in the CBT combined with HRT group (8.69 ± 1.77) compared with the control group (7.87 ± 1.92; t = 2.592, P = 0.011). CONCLUSION: This study demonstrates that CBT combined with HRT significantly reduces anxiety symptoms and tic severity in children with TS, with higher treatment adherence and parental satisfaction. These findings support the potential application of this comprehensive therapeutic approach for TS treatment.

Prevalence of mass social media-induced illness presenting with Tourette-like behavior in Germany between 2019 and 2021.

Starting in 2019, in Germany the first well documented outbreak of mass sociogenic illness induced by social media (mass social media-induced illness; MSMI) occurred presenting with functional Tourette-like behaviors (FTB). This study aimed to provide first data on the prevalence rate of MSMI-FTB in Germany between 2019 and 2021 in the general population. We conducted a large-scale representative population survey in cooperation with the USUMA market and social research institute. Between August and December 2021, n = 2.509 people (mean age: 49.5 years, range: 16-95 years, n = 1.276 females) were randomly selected, visited in their households, interviewed, and asked to answer for themselves, but also for close family members (n = 6.744). Thus, in total, we received answers for n = 9.253 people. Probable MSMI-FTB was found in n = 33 individuals (mean age at onset: 30.5 years, n = 8 females). Based on strict criteria, the diagnosis of MSMI-FTB was considered highly likely in 16/33 individuals (mean age at onset: 25.6 years, n = 2 females) corresponding to prevalence rates of 0.17% (CIlower = 0.10, CIupper = 0.28) and 0.36% (CIlower = 0.25, CIupper = 0.50), respectively. This is the first large-scale, population representative study investigating the prevalence of MSMI-FTB in the general population in Germany between 2019 and 2021. Based on the prevalence rates found, MSMI-FTB is highly relevant for health economy. Accordingly, we suggest educating healthcare professionals and the general public to avoid misdiagnosis and inefficient treatment.

An update on the pharmacological management of Tourette syndrome and emerging treatment paradigms.

INTRODUCTION: Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by tics. Pharmacotherapy is advised for patients whose symptoms affect their quality of life. AREAS COVERED: The authors review the tic phenomenology and TS diagnostic criteria. The bulk of this article focuses on pharmacotherapeutic options for treating tics. They also highlight pharmacotherapies in the research pipeline. EXPERT OPINION: Tic treatment must be tailored to individual needs. Behavioral therapy is the first line of treatment. Most with bothersome tics need pharmacotherapy and rarely, for medication-refractory cases, surgical therapy is indicated. Alpha-2 agonists are considered in patients with mild tics, especially in those with attention deficit with or without hyperactivity. Second-generation antipsychotics like aripiprazole and tiapride may be considered for severe tics. However, prescribers should be mindful of potential side effects, especially drug-induced movement disorders. Botulinum toxin injections may be considered for focal motor tics. Topiramate can be considered when other treatments are ineffective, and its benefits outweigh the risks. The same holds true for vesicular monoamine transporter-2 inhibitors, as they are deemed to be safe and effective in real-world use and open-label trials despite not meeting primary endpoints in placebo-controlled trials. Cannabinoids may be considered in adults if the approaches above do not control tics.

Cytokine expression profiles in children and adolescents with tic disorders.

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.

Efficacy of cannabis-based medicine in the treatment of Tourette syndrome: a systematic review and meta-analysis.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics. It is a condition that affects between 0.3% and 0.7% of children, and its pathophysiology remains largely elusive. TS is associated with structural and functional alterations in corticostriatal circuits and neurochemical imbalances. Even though TS is currently incurable, there are established treatment options available, including behavioral therapy and neuroleptics. The use of cannabis-based medicine for tic management is an emerging therapeutic strategy, although its efficacy is still under investigation. It is hypothesized to interact with the endogenous cannabinoid system, but further research is required to ascertain its safety and effectiveness in TS. AIM: In our systematic review and meta-analysis, we aim to assess the effectiveness of cannabis-based medicine in the treatment of TS. METHODS: We searched PubMed, Cochrane, Scopus, and Web of Sciences until February 2024. We included clinical trials and cohort studies investigating the efficacy of cannabis-based medicine in the treatment of TS. Data extraction focused on baseline characteristics of the included studies and efficacy outcomes, including scores on the Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We conducted the meta-analysis using Review Manager version 5.4. software. We compared the measurements before and after drug intake using mean difference (MD) and 95% confidence interval (CI). RESULTS: In total, 357 articles were identified for screening, with nine studies included in the systematic review and 3 in the meta-analysis. These studies involved 401 adult patients with TS treated with cannabis. YGTSS revealed a significant reduction in total scores (MD = -23.71, 95% CI [-43.86 to -3.55], P = 0.02), PUTS revealed a significant decrease in scores (MD = -5.36, 95% CI [-8.46 to -2.27], P = 0.0007), and Y-BOCS revealed no significant difference in score reduction (MD = -6.22, 95% CI [-12.68 to 0.23], P = 0.06). CONCLUSION: The current study indicates promising and potentially effective outcomes with the use of cannabis-based medicine in mitigating the severity of tics and premonitory urges. However, there is a need for larger, placebo-controlled studies with more representative samples to validate these findings.

Contextual Triggers and Tic Severity Across Life Periods: A Retrospective Analysis in Adults with Tic Disorders.

In tic disorders (TD), tic expression varies across the lifespan and as a function of contextual factors. This study explored connections between tic expression and contextual triggers across life periods in 74 adults (Mage = 23.2) with TDs. The Tic History and Coping Strategies form assessed retrospective self-reports of contextual antecedents, consequences, and tic severity during four life periods (middle school; 9th/10th grade; 11th/12th grade; college/work) and past month. Tics reportedly worsened during and after school in school-aged years and worsened in the evening during college/work years. Stress and anxiety were reported to consistently trigger tics across time. The impact of activities, places, and emotions did not differ across life periods. Attention-based consequences, most prevalent during middle school, were more common than escape- or avoidance-related consequences across all periods. Findings illuminate how contextual factors may influence tics across life periods and underscore the consistent impact of tic-triggering emotions and attention-related consequences.

Neurodevelopmental Disorders Associated with Gut Microbiome Dysbiosis in Children.

The formation of the human gut microbiome initiates in utero, and its maturation is established during the first 2-3 years of life. Numerous factors alter the composition of the gut microbiome and its functions, including mode of delivery, early onset of breastfeeding, exposure to antibiotics and chemicals, and maternal stress, among others. The gut microbiome-brain axis refers to the interconnection of biological networks that allow bidirectional communication between the gut microbiome and the brain, involving the nervous, endocrine, and immune systems. Evidence suggests that the gut microbiome and its metabolic byproducts are actively implicated in the regulation of the early brain development. Any disturbance during this stage may adversely affect brain functions, resulting in a variety of neurodevelopmental disorders (NDDs). In the present study, we reviewed recent evidence regarding the impact of the gut microbiome on early brain development, alongside its correlation with significant NDDs, such as autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, cerebral palsy, fetal alcohol spectrum disorders, and genetic NDDs (Rett, Down, Angelman, and Turner syndromes). Understanding changes in the gut microbiome in NDDs may provide new chances for their treatment in the future.

An Online Mindfulness-Based Group Intervention for Tics: A Pilot Randomized Controlled Trial.

BACKGROUND: Current treatments for Tourette syndrome (TS) and persistent tic disorder (PTD) are often insufficiently effective, inaccessible, and frequently associated with adverse events. Thus, we must continue to develop and test effective, accessible, and safe treatment options. OBJECTIVE: We aimed to conduct a pilot randomized controlled trial (RCT) comparing a novel, videoconference-delivered group mindfulness-based intervention for tics (MBIT) to videoconference-delivered group psychoeducation, relaxation, and supportive therapy (PRST) for adults with TS or PTD. METHODS: Thirty-two adults with TS or PTD were randomly assigned to receive 8 weeks of either MBIT or PRST. Tic severity, tic-related impairment, and global improvement were assessed by a trained, independent evaluator who was masked to treatment condition at baseline (week 0), posttreatment (week 9), 1-month follow-up, and 6-month follow-up. All study procedures were conducted online via secure videoconferencing. RESULTS: Twenty-eight participants began treatment and were included in analyses. MBIT, relative to PRST, was associated with a significantly greater decline in tic severity (d = 0.85) and tic-related impairment (d = 0.99) from baseline to posttreatment. Treatment response was significantly higher in MBIT (69%) than in PRST (13%). Neither treatment resulted in serious adverse effects. The durability of treatment outcomes is also reported and discussed. CONCLUSIONS: The results from this pilot RCT suggest that videoconference-delivered group MBIT may be an efficacious, accessible, and safe intervention for adults with tics. Future research is necessary to confirm these preliminary findings. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Functional Tic-like Behaviors: From the COVID-19 Pandemic to the Post-Pandemic Era.

During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis.

We've all been wrong about provisional tic disorder.

BACKGROUND: Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up. METHODS: Prospective study of 89 children with tics starting 0-9 months ago (median 4 months), fewer than half from clinical sources. Follow-up at 12 (± 24, 36, 48) months after the first tic. RESULTS: At study entry, many children had ADHD (39), an anxiety disorder (27), OCD (9) or enuresis (17). All had at least two current tics, with a mean total since onset of 6.9 motor and 2.0 phonic tics. Forty-one had experienced a complex tic, and 69 could suppress some tics. Tics were clinically meaningful: 64 had tics severe enough for a clinical trial, and 76 families sought medical attention for the tics. At 12 months, 79 returned, and 78 still had tics. Of these, 29 manifested no tics during history and extended examination, but only via audio-visual monitoring when the child was seated alone. Only 12/70 now had plans to see a doctor for tics. Most who returned at 2-4 years still had tics known to the child and family, but medical impact was low. CONCLUSIONS: Our results do not contradict previous data, but overturn clinical lore. The data strongly argue against the longstanding but arbitrary tradition of separating tic disorders into recent-onset versus chronic.

A Critical Examination of the Clinical Diagnosis of Functional Tic-like Behaviors.

BACKGROUND: Since the COVID-19 pandemic, movement disorder clinics have seen an increase in patients with an unusual type of tic-like symptoms: young adults with abrupt onset complex behaviors. It was quickly suspected that these patients suffered from functional neurological symptoms, later named Functional Tic-Like Behaviors (FTLB). Subsequent research on the differential diagnosis between FTLB and tics has been substantial and led to the development of diagnostic checklists. OBJECTIVES: We conducted a theoretical reappraisal of the FTLB literature to clarify the validity of the concept and its diagnostic implications. METHODS: This paper addresses several key aspects of the current FTLB literature: circular reasoning, the complications of the FTLB phenomenology and demographics, the impact of FTLB on tic literature at large, and issues with alignment of the FTLB concept with the diagnostic criteria for functional disorders. RESULTS: The clinical approach to FTLB might involve circular reasoning due to a lack of clinical benchmarks. The FTLB phenomenology and demographics may need more work to ensure a lack of bias and a proper description of this patient group including a clear distinction from tics. The impact of the FTLB discussion on the wider literature needs consideration. The validation of positive signs may help with both these endeavors and pave way to the inclusion of FTLB within psychiatric classification systems. Furthermore, the coexistence of FTLB and tics within the same patient needs to be addressed. CONCLUSION: More research may be needed to fully establish the diagnosis of FTLB and differentiate it from tics.

Functional brain networks associated with the urge for action: Implications for pathological urge.

Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed.

Psychometric Properties of the MOVES Scale for Tourette Syndrome and Comorbidities in a Chinese Cultural Context.

The Motor tic, Obsessions and Compulsions, Vocal tic Evaluation Survey (MOVES) is a widely used screening tool for Tourette syndrome (TS) and associated comorbidities. This study evaluated its applicability for children in China using 7,125 participants from the National Center for Children's Health (Beijing). Psychometric evaluations included exploratory and confirmatory factor analysis, yielding a 16-item, four-factor model that explained 55.11% of the variance and demonstrated good internal consistency (Cronbach's alpha = 0.88) and test-retest reliability (ICC = 0.86). The scale showed strong convergent, discriminant, and criterion-related validity and was significantly correlated with other established TS scales. The results affirm the reliability and validity of the MOVES for screening TS in Asian contexts, addressing a crucial gap in the region's TS assessment tools.

Gamified Closed-Loop Intervention Enhances Tic Suppression in Children: A Randomized Trial.

BACKGROUND: Gamification of behavioral intervention for tic disorders (TDs) potentially enhances compliance and offers key clinical advantages. By delivering immediate positive feedback upon tic-suppression, games may counteract negative reinforcement, which presumably contribute to tic consolidation by relieving uncomfortable premonitory urges. OBJECTIVES: We developed a gamified protocol (XTics), which leverages this potential by combining gamified tic-triggering with immediate feedback, and evaluated its clinical value in enhancing tic suppression. METHODS: XTics encompasses two conditions: Immediate and Contingent Reward (ICR), where game progression is contingent upon successful tic suppression, and Delayed Reward (DR), where game events' outcomes are random. Employing a randomized crossover design, 35 participants (aged 7-15 years) underwent daily gaming sessions over a week per condition. Improvements in our primary measures, including the inter-tic interval (ITI) and tic severity assessment by blinded evaluators (Yale Global Tic Severity-Total Tic Score [YGTSS-TTS], Rush), and parents (Parent Tic Questionnaire [PTQ]), were compared between ICR and DR, and assessed across conditions for the 4-week protocol. RESULTS: No participant voluntarily left the study before completing its two-phase protocol. As expected, ITI showed significantly larger improvement (Z = 4.19, P = 2.85 × 10-5) after ICR (1442 ± 2250%) versus DR (242 ± 493%) training, increasing at a higher pace (t(67) = 3.15, P = 0.0025). Similarly, Rush tic severity scores reduced more post-ICR versus DR (t(47) = 3.47, P = 0.002). We observed a clinically significant reduction of 25.69 ± 23.39% in YGTSS-TTS following a f4-week protocol including both conditions. Parent-reported tic severity decreased by 42.99 ± 31.69% from baseline to 3 months post-treatment. CONCLUSIONS: The combination of gamified tic-triggering with immediate and contingent rewards demonstrates a promising approach for enhancing treatment efficacy in TDs, boosting traditional therapeutic methods. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Surgical Concepts and Long-term Outcomes of Thalamic Deep Brain Stimulation in Patients with Severe Tourette Syndrome: A Single-center Experience.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by tic movements. Deep brain stimulation (DBS) may be a treatment option for severe cases refractory to medical and behavioral therapies. In this study, we reviewed the surgical techniques used for DBS in patients with severe TS and its clinical outcomes and sought to determine the optimal surgical procedure and current issues based on our experience and the literature. A total of 14 patients, consisting of 13 men and 1 woman, who underwent centromedian thalamic DBS and were followed up for a mean duration of 2.3 ± 1.0 years, participated in this study. The mean Yale Global Tic Severity Scale severity score significantly improved from 41.4 ± 7.0 at baseline to 19.8 ± 11.4 at 6 months (P = 0.01) and 12.7 ± 6.2 at the last follow-up (P < 0.01). Moreover, the mean Yale Global Tic Severity Scale impairment score significantly improved from 47.1 ± 4.7 at baseline to 23.1 ± 11.1 at 6 months (P < 0.01) and 7.6 ± 2.9 at the last follow-up (P < 0.01). However, there were problems with continuous postoperative monitoring (three cases were lost to follow-up) and surgery-related adverse events, including one case each of lead misplacement and a delayed intracerebral hemorrhage due to severe self-injurious tics. This study aimed to highlight not only the clinical efficacy of DBS for TS but also its challenges. Clinicians should understand the three-dimensional brain anatomy so that they can perform precise surgical procedures, avoid adverse events, and achieve favorable outcomes of DBS for TS.

Exploring protocol development: Implementing systematic contextual memory to enhance real-time fMRI neurofeedback.

Objective: The goal of this study was to explore the development and implementation of a protocol for real-time fMRI neurofeedback (rtfMRI-nf) and to assess the potential for enhancing the selective brain activation using stimuli from Virtual Reality (VR). In this study we focused on two specific brain regions, supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). Publications by other study groups have suggested impaired function in these specific brain regions in patients with the diagnoses Attention Deficit Hyperactivity Disorder (ADHD) and Tourette's Syndrome (TS). This study explored the development of a protocol to investigate if attention and contextual memory may be used to systematically strengthen the procedure of rtfMRI-nf. Methods: We used open-science software and platforms for rtfMRI-nf and for developing a simulated repetition of the rtfMRI-nf brain training in VR. We conducted seven exploratory tests in which we updated the protocol at each step. During rtfMRI-nf, MRI images are analyzed live while a person is undergoing an MRI scan, and the results are simultaneously shown to the person in the MRI-scanner. By focusing the analysis on specific regions of the brain, this procedure can be used to help the person strengthen conscious control of these regions. The VR simulation of the same experience involved a walk through the hospital toward the MRI scanner where the training sessions were conducted, as well as a subsequent simulated repetition of the MRI training. The VR simulation was a 2D projection of the experience.The seven exploratory tests involved 19 volunteers. Through this exploration, methods for aiming within the brain (e.g. masks/algorithms for coordinate-system control) and calculations for the analyses (e.g. calculations based on connectivity versus activity) were updated by the project team throughout the project. The final procedure involved three initial rounds of rtfMRI-nf for learning brain strategies. Then, the volunteers were provided with VR headsets and given instructions for one week of use. Afterward, a new session with three rounds of rtfMRI-nf was conducted. Results: Through our exploration of the indirect effect parameters - brain region activity (directed oxygenated blood flow), connectivity (degree of correlated activity in different regions), and neurofeedback score - the volunteers tended to increase activity in the reinforced brain regions through our seven tests. Updates of procedures and analyses were always conducted between pilots, and never within. The VR simulated repetition was tested in pilot 7, but the role of the VR contribution in this setting is unclear due to underpowered testing. Conclusion: This proof-of-concept protocol implies how rtfMRI-nf may be used to selectively train two brain regions (SMA and rIFG). The method may likely be adapted to train any given region in the brain, but readers are advised to update and adapt the procedure to experimental needs.

Neural representations of statistical and rule-based predictions in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is a disorder characterised by motor and vocal tics, which may represent habitual actions as a result of enhanced learning of associations between stimuli and responses (S-R). In this study, we investigated how adults with GTS and healthy controls (HC) learn two types of regularities in a sequence: statistics (non-adjacent probabilities) and rules (predefined order). Participants completed a visuomotor sequence learning task while EEG was recorded. To understand the neurophysiological underpinnings of these regularities in GTS, multivariate pattern analyses on the temporally decomposed EEG signal as well as sLORETA source localisation method were conducted. We found that people with GTS showed superior statistical learning but comparable rule-based learning compared to HC participants. Adults with GTS had different neural representations for both statistics and rules than HC adults; specifically, adults with GTS maintained the regularity representations longer and had more overlap between them than HCs. Moreover, over different time scales, distinct fronto-parietal structures contribute to statistical learning in the GTS and HC groups. We propose that hyper-learning in GTS is a consequence of the altered sensitivity to encode complex statistics, which might lead to habitual actions.