Automated Quantification of Eye Tics Using Computer Vision and Deep Learning Techniques.

BACKGROUND: Tourette syndrome (TS) tics are typically quantified using "paper and pencil" rating scales that are susceptible to factors that adversely impact validity. Video-based methods to more objectively quantify tics have been developed but are challenged by reliance on human raters and procedures that are resource intensive. Computer vision approaches that automate detection of atypical movements may be useful to apply to tic quantification. OBJECTIVE: The current proof-of-concept study applied a computer vision approach to train a supervised deep learning algorithm to detect eye tics in video, the most common tic type in patients with TS. METHODS: Videos (N = 54) of 11 adolescent patients with TS were rigorously coded by trained human raters to identify 1.5-second clips depicting "eye tic events" (N = 1775) and "non-tic events" (N = 3680). Clips were encoded into three-dimensional facial landmarks. Supervised deep learning was applied to processed data using random split and disjoint split regimens to simulate model validity under different conditions. RESULTS: Area under receiver operating characteristic curve was 0.89 for the random split regimen, indicating high accuracy in the algorithm's ability to properly classify eye tic vs. non-eye tic movements. Area under receiver operating characteristic curve was 0.74 for the disjoint split regimen, suggesting that algorithm generalizability is more limited when trained on a small patient sample. CONCLUSIONS: The algorithm was successful in detecting eye tics in unseen validation sets. Automated tic detection from video is a promising approach for tic quantification that may have future utility in TS screening, diagnostics, and treatment outcome measurement. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantifying tics: Best practices and design considerations for video-based tic coding in research.

Tic disorders (TD), including Tourette Syndrome, are characterized by involuntary, repetitive movements and/or vocalizations that can lead to persistent disability and impairment across the lifespan. Existing research demonstrates that video-based behavioral coding (VBBC) methods can be used to reliably quantify tics, enabling a more objective approach to tic measurement above and beyond standardly used TD questionnaires. VBBC is becoming more popular given the ease and ubiquity of obtaining patient videos. However, rigor and reproducibility of this work has been limited by undescribed and unstandardized approaches to using VBBC methods in TD research. The current paper describes "best practices" for VBBC in TD research, which have been tested and refined in our research over the past 15+ years, including considerations for data acquisition, coding implementation, interrater reliability demonstration, and methods reporting. We also address ethical considerations for researchers using this method.

Cognitive performance of youth with primary generalized anxiety disorder versus primary obsessive-compulsive disorder.

BACKGROUND: Despite gains made in the study of childhood anxiety, differential diagnosis remains challenging because of indistinct boundaries between disorders and high comorbidity. This is certainly true for generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as they share multiple cognitive processes (e.g., rumination, intolerance of uncertainty, and increased attention to threat). Disentangling such cognitive characteristics and, subsequently, underlying mechanisms could serve to inform assessment and treatment practices, and improve prognoses. METHODS: The current study sought to compare the cognitive performance (working memory, visuospatial memory, planning ability/efficiency, and cognitive flexibility), indexed by the Cambridge Neuropsychological Automated Battery (CANTAB) among three nonoverlapping groups of youth: (1) those diagnosed with OCD (n = 28), (2) those diagnosed with GAD, not OCD (n = 34), and (3) typically-developing controls (TDC) (n = 65). RESULTS: Results showed that OCD and GAD youth demonstrated neurocognitive deficits in planning ability/efficiency, cognitive flexibility, and visual processing when compared to TDC, with potential diagnostic specificity such that youth with GAD or OCD had unique deficits compared to TDC and to one another. Specifically, youth with OCD demonstrated significantly impaired planning ability compared to youth in the GAD and TDS groups, whereas youth with GAD demonstrated greater cognitive inflexibility and delayed visual processing compared to youth in the OCD and TDC groups. CONCLUSIONS: Future studies should expand upon these findings with more comprehensive assessment of cognitive functioning by including self- and parent-report forms, and neuroimaging to link behavioral findings with subjective ratings and neurocircuitry. Altogether, data can then inform future assessment and treatment targets.

Tic Treatment Goes Tech: A Review of TicHelper.com.

TicHelper.com ("TicHelper") is an interactive online treatment program for youth with chronic tic disorders (CTDs) or Tourette Syndrome (TS) and their parents. It is based on Comprehensive Behavioral Intervention for Tics (CBIT), an individual, outpatient therapy protocol shown to effectively reduce tics in randomized controlled trials. The TicHelper website offers a user-friendly dashboard that is effective in making it easy to navigate through different treatment modules. Modules parallel core CBIT procedures and consist of interactive exercises, informational videos, and self-report ratings. TicHelper has some weaknesses (e.g., no outcomes research specific to the program has been published to date); however, its strengths (easily navigable, clear instructions, appropriate content) outweigh its weaknesses, making it a potentially useful dissemination tool to make CBIT more accessible to families and youth with tics.

Tic-related activity restriction as a predictor of emotional functioning and quality of life.

OBJECTIVES: Tourette Syndrome (TS) is a chronic neuropsychiatric condition that frequently persists into adulthood. Existing research has identified demographic and symptom-level variables associated with psychopathology and poor quality of life in TS. However, behavior patterns associated with enhanced or adaptive psychological and global functioning among adults with TS have yet to be empirically identified. The current study examined whether tic-specific activity restriction is related to emotional functioning and quality of life in adults with TS. METHODS: Participants were 509 adults from the Tourette Syndrome Impact Survey who completed self-report measures of demographics, tic severity, emotional functioning, quality of life, and tic-related general and social activity restriction. RESULTS: Partial correlations controlling for tic severity indicated that tic-related general and social activity restriction were significantly correlated with lower quality of life and poorer emotional functioning. Hierarchical linear regression models indicated that activity restriction significantly predicted lower quality of life and poorer emotional functioning when controlling for tic severity and demographic variables. CONCLUSIONS: Adults who restrict fewer activities due to tics, regardless of tic severity, experience greater quality of life and better emotional functioning. Clinically, adults with chronic tics may benefit from interventions focused on enhancing engagement in valued life activities.

Sensory intolerance: latent structure and psychopathologic correlates.

BACKGROUND: Sensory intolerance refers to high levels of distress evoked by everyday sounds (e.g., sounds of people chewing) or commonplace tactile sensations (e.g., sticky or greasy substances). Sensory intolerance may be associated with obsessive-compulsive (OC) symptoms, OC-related phenomena, and other forms of psychopathology. Sensory intolerance is not included as a syndrome in current diagnostic systems, although preliminary research suggests that it might be a distinct syndrome. OBJECTIVES: First, to investigate the latent structure of sensory intolerance in adults; that is, to investigate whether it is syndrome-like in nature, in which auditory and tactile sensory intolerance co-occur and are associated with impaired functioning. Second, to investigate the psychopathologic correlates of sensory intolerance. In particular, to investigate whether sensory intolerance is associated with OC-related phenomena, as suggested by previous research. METHOD: A sample of 534 community-based participants were recruited via Amazon.com's Mechanical Turk program. Participants completed measures of sensory intolerance, OC-related phenomena, and general psychopathology. RESULTS: Latent class analysis revealed two classes of individuals: those who were intolerant of both auditory and tactile stimuli (n=150), and those who were relatively undisturbed by auditory or tactile stimuli (n=384). Sensory-intolerant individuals, compared to those who were comparatively sensory tolerant, had greater scores on indices of general psychopathology, more severe OC symptoms, a higher likelihood of meeting caseness criteria for OC disorder, elevated scores on measures of OC-related dysfunctional beliefs, a greater tendency to report OC-related phenomena (e.g., a greater frequency of tics), and more impairment on indices of social and occupational functioning. Sensory-intolerant individuals had significantly higher scores on OC symptoms even after controlling for general psychopathology. CONCLUSIONS: Consistent with recent research, these findings provide further evidence for a sensory intolerance syndrome. The findings provide a rationale for conducting future research for determining whether a sensory intolerance syndrome should be included in the diagnostic nomenclature.

Evidence base update for psychosocial treatments for pediatric obsessive-compulsive disorder.

Pediatric obsessive-compulsive disorder (OCD) is a chronic and impairing condition that often persists into adulthood. Barrett, Farrell, Pina, Peris, and Piacentini (2008), in this journal, provided a detailed review of evidence-based psychosocial treatments for youth with OCD. The current review provides an evidence base update of the pediatric OCD psychosocial treatment literature with particular attention to advances in the field as well as to the methodological challenges inherent in evaluating such findings. Psychosocial treatment studies conducted since the last review are described and evaluated according to methodological rigor and evidence-based classification using the JCCAP evidence-based treatment evaluation criteria (Southam-Gerow & Prinstein, this issue). Findings from this review clearly converge in support of cognitive-behavioral therapy as an effective and appropriate first line treatment for youth with OCD (either alone or in combination with medication). Although no treatment for pediatric OCD has yet to be designated as "well-established," both individual and individual family-based treatments have been shown to be "probably efficacious." Moderators and predictors of treatment outcome are discussed as are the areas where we have advanced the field and the areas where we have room to grow. The methodological and clinical challenges inherent in a review of the evidence base are reviewed. Finally, future research directions are outlined.

The role of parental perceptions of tic frequency and intensity in predicting tic-related functional impairment in youth with chronic tic disorders.

Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with chronic tic disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency.

Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics.

To establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day research planning summit with 46 individuals representing key stakeholder groups, and community response to summit reports. Four high-priority research domains were identified: (a) expanding treatment access, (b) improving treatment outcomes, (c) optimizing treatment within a broader care model, and (d) evaluating outcomes beyond tic severity. Community-engaged participatory research models can efficiently delineate clear and actionable priorities for clinical research. This approach holds promise for improving the impact of clinical research in TDs and other neuropsychiatric disorders.

Long-term follow-up of acceptance-enhanced behavior therapy for trichotillomania.

Acceptance-enhanced behavior therapy for trichotillomania (AEBT-TTM) is effective in reducing trichotillomania (TTM) symptoms, but the durability of treatment effects remains in question. This study analyzed 6-month follow-up data from a large randomized clinical trial comparing AEBT-TTM to an active psychoeducation and supportive therapy control (PST). Adults with TTM (N=85; 92% women) received 10 sessions of AEBT-TTM or PST across 12 weeks. Independent evaluators assessed participants at baseline, post-treatment, and 6 months follow-up. For both AEBT-TTM and PST, self-reported and evaluator-rated TTM symptom severity decreased from baseline to follow-up. TTM symptoms did not worsen from post-treatment to follow-up. At follow-up, AEBT-TTM and PST did not differ in rates of treatment response, TTM diagnosis, or symptom severity. High baseline TTM symptom severity was a stronger predictor of high follow-up severity for PST than for AEBT-TTM, suggesting AEBT-TTM may be a better option for more severe TTM. Results support the efficacy of AEBT-TTM and show that treatment gains were maintained over time. Although AEBT-TTM yielded lower symptoms at post-treatment, 6-month follow-up outcomes suggest AEBT-TTM and PST may lead to similar symptom levels in the longer term. Future research should examine mechanisms that contribute to long-term gain maintenance.

The impact of Tourette Syndrome in adults: results from the Tourette Syndrome impact survey.

Chronic tic disorders (CTD) are characterized by motor and/or vocal tics. Existing data on the impact of tics in adulthood is limited by small, treatment-seeking samples or by data aggregated across adults and children. The current study explored the functional impact of tics in adults using a nationwide sample of 672 participants with a self-reported CTD. The impact of tics on physical, social, occupational/academic, and psychological functioning was assessed. Results suggested mild to moderate functional impairment and positive correlations between impairment and tic severity. Notable portions of the sample reported social or public avoidance and experiences of discrimination resulting from tics. Compared to previously reported population norms, participants had more psychological difficulties, greater disability, and lower quality of life. The current study suggests that CTDs can adversely impact functioning in adults and highlights the need for clinical interventions and systemic efforts to address tic-related impairments.

Response Inhibition in Youth Undergoing Intensive Treatment for Obsessive Compulsive Disorder.

Response Inhibition (RI) is the ability to suppress behaviors that are inappropriate for a given context. Obsessive-compulsive disorder (OCD) has been associated with impaired RI in adults as measured by the Stop Signal Task (SST). Conflicting results have been found in terms of the relationship between OCD severity and SST performance, and no studies to date have examined the relationship between SST and response to OCD treatment. Also relatively unknown is whether RI performance in OCD is associated with developmental or gender differences. This naturalistic study examined the relationship between SST performance, OCD severity, and OCD treatment response in a pediatric sample undergoing intensive treatment involving exposure and response prevention and medication management (n = 36). The SST and Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS) were administered at admission and program discharge. OCD severity was not significantly related to stop signal reaction time (SSRT) in the whole sample and among subgroups divided by age and gender. Baseline SSRT and SSRT change did not predict CYBOCS change across treatment in the whole sample, but exploratory analyses indicated both were significant predictors among female adolescents. Results suggest there may be developmental gender differences in the relationship between RI and clinical improvement in pediatric OCD.

Integrating Causal Discovery and Clinically-Relevant Insights to Explore Directional Relationships between Autistic Features, Sex at Birth, and Cognitive Abilities.

Prevalence in autism spectrum disorder (ASD) diagnosis has long been strongly male-biased. Yet, consensus has not been reached on mechanisms and clinical features that underlie sex-based discrepancies. Whereas females may be under-diagnosed because of inconsistencies in diagnostic/ascertainment procedures (sex-biased criteria, social camouflaging), diagnosed males may have exhibited more overt behaviors (e.g., hyperactivity, aggression) that prompted clinical evaluation. Applying a novel network-theory-based approach, we extracted data-driven, clinically-relevant insights from a large, well-characterized sample (Simons Simplex Collection) of 2175 autistic males (Ages = 8.9±3.5 years) and 334 autistic females (Ages = 9.2±3.7 years). Exploratory factor analysis (EFA) and expert clinical review reduced data dimensionality to 15 factors of interest. To offset inherent confounds of an imbalanced sample, we identified a subset of males (N=331) matched to females on key variables (Age, IQ) and applied data-driven CDA using Greedy Fast Causal Inference (GFCI) for three groups (All Females, All Males, and Matched Males). Structural equation modeling (SEM) extracted measures of model fit and effect sizes for causal relationships between sex, age, and, IQ on EFA-selected factors capturing phenotypic representations of autism across sensory, social, and restricted and repetitive behavior domains. Our methodology unveiled sex-specific directional relationships to inform developmental outcomes and targeted interventions.

A Mobile Application Adjunct to Augment Cognitive-Behavioral Group Therapy for Adolescents with Social Anxiety: Feasibility and Acceptability Results from the Wiring Adolescents with Social Anxiety via Behavioral Interventions Pilot Trial.

Objective: Cognitive-Behavioral Group Therapy (CBGT) is an established treatment for Social Anxiety (SA). However, diagnostic recovery rate is only 20.5% in CBGT, and up to 50% of patients remain symptomatic posttreatment. Using videocalls to deliver digital CBGT (dCBGT) is feasible, cost-effective, and efficacious. Yet, the impact of dCBGT on social functioning remains limited, as dCBGT does not offer opportunities for monitoring cognition and behavior in social situations. Wiring Adolescents with Social Anxiety via Behavioral Interventions (WASABI), a clinician-assisted application that uses ecological momentary assessments (EMAs), cognitive bias tests, and clinical self-reports, was investigated as an adjunct to dCBGT. Methods: A prospective, parallel arm, double-blind randomized controlled trial was employed in 24 SA adolescents randomly assigned to dCBGT versus dCBGT plus WASABI. Results: Study completion rates (83%) and exit survey data indicated that WASABI is feasible and acceptable. Engagement with EMAs varied from four to 244 EMAs completed per person. Cognitive bias tests and clinical self-reports were completed at least weekly by 53% and 69% of participants, respectively. While standard tests did not reveal statistically significant differences between dCBGT plus WASABI and dCBGT alone, effect sizes were greater for dCBGT plus WASABI on symptom severity, social skills, and functioning. Conclusions: Despite the small sample, preliminary results suggest that WASABI is feasible, acceptable, and may be an effective augmentation tool for treating SA in teenagers.

Evaluating the feasibility, acceptability, and preliminary effectiveness of tele-comprehensive behavior therapy for tics (teleCBIT) for Tourette syndrome in youth and adults.

INTRODUCTION: Comprehensive behavioral intervention for tics (CBIT) is an efficacious, first-line treatment for Tourette syndrome (TS) and other chronic or persistent tic disorders. However, CBIT's public health impact has been limited by suboptimal treatment access. Preliminary research has shown that providing CBIT over videoconference (teleCBIT) is a promising delivery method for patients who cannot access in-person care. However, extant studies have been small efficacy trials focused only on pediatric patients. Replication of these studies is needed in additional treatment settings and across a wider age range of patients, especially in light of advances in telehealth technology and increasing telehealth adoption among practitioners. METHODS: We conducted a single-arm trial to evaluate the feasibility, acceptability, and effectiveness of teleCBIT embedded in comprehensive, medical tic specialty clinics. From October 2016 to September 2018, patients were offered teleCBIT at their usual care appointments. Those who were interested and met inclusion/exclusion criteria received 8 sessions of CBIT guided by a manualized protocol. An independent evaluator, masked to treatment progress, administered assessments at baseline, post-treatment, and 3 and 6 months after treatment. RESULTS: Twenty-five percent of patients who were offered treatment initiated teleCBIT through the study, and all treatment initiators completed treatment. From pre- to post-treatment, decreases in Yale Global Tic Severity Scale (YGTSS) total tic severity scores showed a large effect size among pediatric patients (n = 19; t = 5.72, P < 0.001, d = 1.31) and a medium-to-large effect size for adult patients (n = 10, t = 1.41, P = 0.096, d = 0.664). Thirteen of 19 pediatric patients (68%) and 6 of 10 adult patients (60%) had a positive global treatment response at post-treatment. Patients rated the treatment as highly satisfactory. Ninety-three percent of sessions were free of substantial technical problems. DISCUSSION: Within the context of medical tic specialty clinics, teleCBIT demonstrated strong evidence of feasibility, acceptability, and preliminary effectiveness comparable to in-person treatment for both pediatric and adult patients. TeleCBIT warrants study in future research on enhancing care systems for patients with TS. TRIAL REGISTRY: https://clinicaltrials.gov/ct2/keydates/NCT04007913.

Optimizing Individual Targeting of Fronto-Amygdala Network with Transcranial Magnetic Stimulation (TMS): Biophysical, Physiological and Behavioral Variations in People with Methamphetamine Use Disorder.

Background: Previous studies in people with substance use disorders (SUDs) have implicated both the frontopolar cortex and amygdala in drug cue reactivity and craving, and amygdala-frontopolar coupling is considered a marker of early relapse risk. Accumulating data highlight that the frontopolar cortex can be considered a promising therapeutic target for transcranial magnetic stimulation (TMS) in SUDs. However, one-size-fits-all approaches to TMS targets resulted in substantial variation in both physiological and behavioral outcomes. Individualized TMS approaches to target cortico-subcortical circuits like amygdala-frontopolar have not yet been investigated in SUDs. Objective: Here, we (1) defined individualized TMS target location based on functional connectivity of the amygdala-frontopolar circuit while people were exposed to drug-related cues, (2) optimized coil orientation based on maximizing electric field (EF) perpendicular to the individualized target, and (3) harmonized EF strength in targeted brain regions across a population. Method: MRI data including structural, resting-state, and task-based fMRI data were collected from 60 participants with methamphetamine use disorders (MUDs). Craving scores based on a visual analog scale were collected immediately before and after the MRI session. We analyzed inter-subject variability in the location of TMS targets based on the maximum task-based connectivity between the left medial amygdala (with the highest functional activity among subcortical areas during drug cue exposure) and frontopolar cortex using psychophysiological interaction (PPI) analysis. Computational head models were generated for all participants and EF simulations were calculated for fixed vs. optimized coil location (Fp1/Fp2 vs. individualized maximal PPI location), orientation (AF7/AF8 vs. orientation optimization algorithm), and stimulation intensity (constant vs. adjusted intensity across the population). Results: Left medial amygdala with the highest (mean ± SD: 0.31±0.29) functional activity during drug cue exposure was selected as the subcortical seed region. Amygdala-to-whole brain PPI analysis showed a significant cluster in the prefrontal cortex (cluster size: 2462 voxels, cluster peak in MNI space: [25 39 35]) that confirms cortico-subcortical connections. The location of the voxel with the most positive amygdala-frontopolar PPI connectivity in each participant was considered as the individualized TMS target (mean ± SD of the MNI coordinates: [12.6 64.23 -0.8] ± [13.64 3.50 11.01]). Individual amygdala-frontopolar PPI connectivity in each participant showed a significant correlation with VAS scores after cue exposure (R=0.27, p=0.03). Averaged EF strength in a sphere with r = 5mm around the individualized target location was significantly higher in the optimized (mean ± SD: 0.99 ± 0.21) compared to the fixed approach (Fp1: 0.56 ± 0.22, Fp2: 0.78 ± 0.25) with large effect sizes (Fp1: p = 1.1e-13, Hedges'g = 1.5, Fp2: p = 1.7e-5, Hedges'g = 1.26). Adjustment factor to have identical 1 V/m EF strength in a 5mm sphere around the individualized targets ranged from 0.72 to 2.3 (mean ± SD: 1.07 ± 0.29). Conclusion: Our results show that optimizing coil orientation and stimulation intensity based on individualized TMS targets led to stronger electric fields in the targeted brain regions compared to a one-size-fits-all approach. These findings provide valuable insights for refining TMS therapy for SUDs by optimizing the modulation of cortico-subcortical circuits.

Caregiver Perspectives on the Health Care System for Tic Disorders: Utilization and Barriers.

OBJECTIVE: This study aimed to understand health care experiences among a sample of caregivers of children with TDs to inform future directions for improving the health care system. METHODS: We conducted a survey of caregivers of youth with TDs and used descriptive statistics and quantitative analyses to characterize the health care utilization practices of the sample. RESULTS: The majority (70%) of families first consulted their pediatrician/primary care provider, and caregivers reported receiving care in line with current best practice guidelines. However, caregivers in the current sample perceived a lack of knowledgeability on the part of their first providers, which significantly predicted more providers seen and also reported difficulty finding specialty providers (63% of the sample reported difficulty finding a treatment provider who understood tics). CONCLUSION: Results suggest that improving caregiver satisfaction with early health care experiences for their child's TD may help to relieve the burden on families and the health care system more broadly, along with continued efforts to increase the number of specialty providers available.

The CBIT+TMS Trial: study protocol for a two-phase randomized controlled trial testing neuromodulation to augment behavior therapy for youth with chronic tics.

Background: Comprehensive Behavioral Intervention for Tics (CBIT) is a first-line treatment for tic disorders that aims to improve controllability over tics that an individual finds distressing or impairing. However, it is only effective for approximately half of patients. Supplementary motor area (SMA)-directed neurocircuitry plays a strong role in motor inhibition, and activity in this region is thought to contribute to tic expression. Targeted modulation of SMA using transcranial magnetic stimulation (TMS) may increase CBIT efficacy by improving patient ability to implement tic controllability behaviors. Methods: The CBIT+TMS trial is a two-phase, milestone driven early-stage randomized controlled trial. The trial will test whether augmenting CBIT with inhibitory, noninvasive stimulation of SMA with TMS modifies activity in SMA-mediated circuits and enhances tic controllability in youth ages 12-21 years with chronic tics. Phase 1 will directly compare two rTMS augmentation strategies (1Hz rTMS vs. cTBS) vs. sham in N = 60 participants. Quantifiable, a priori "Go/No Go Criteria" guide the decision to proceed to Phase 2 and selection of the optimal TMS regimen. Phase 2 will compare the optimal regimen vs. sham and test the link between neural target engagement and clinical outcomes in a new sample of N = 60 participants. Discussion: This clinical trial is one of few to date testing TMS augmentation of therapy in a pediatric sample. Results will provide insight into whether TMS is a potentially viable strategy for enhancing CBIT efficacy and reveal potential neural and behavioral mechanisms of change. Trial registration: ClinicalTrials.gov Identifier: NCT04578912.