Multimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics - PROJECT SUMMARY The overall objective of this proposal is to conduct the first mechanistic clinical trial of pediatric Comprehensive Behavioral Intervention for Tics (CBIT) to identify bio-behavioral predictors and correlates of response and the most potent aspects of CBIT delivery. Chronic tics affect 1-3% of youth in the US and are a disabling neuropsychiatric symptom associated with multiple childhood-onset mental disorders. CBIT is the current first-line, gold-standard treatment for tics and focuses on skills to enhance voluntary tic suppression and reduce tic triggers. However, about 50% of youth do not benefit from CBIT. The current study aims to use multimodal measurements to identify predictors of response (for whom does CBIT work?), the therapeutic processes that activate change (what are the potent aspects of CBIT delivery?), and correlates of response (what changes occur in patients whose tics improve?). Study hypotheses, based on the literature and our preliminary data, predict that CBIT relies upon, engages, and strengthens connectivity within and between functional brain networks that support top-down control over motor functions. Youth ages 10-17 years with chronic tics (N = 100) will complete a course of 8 outpatient, weekly sessions of CBIT and pre-, post-, and 3-month follow up assessments. Multimodal assessments will include: 1) neural measures of functional connectivity among the brain's large-scale functional networks using fMRI and EEG during rest and tic expression and suppression, 2) direct-observation behavioral measurement of tics, and 3) psychosocial measures, including assessments of clinical symptoms and patient-centered outcome measures informed by preliminary data and our Patient Advisory Board. CBIT process will be assessed via a novel video-based behavioral coding of CBIT sessions. This project has the potential to directly benefit patients both immediately and in the long-term. Results will have a downstream impact on clinical practice by informing individualized treatment planning and efforts to streamline and improve CBIT quality. Results will also have an upstream impact on treatment development by identifying novel neural targets for intervention and strategies for improving CBIT outcomes via refinement or adjunctive procedures.