Project Summary/Abstract Psychogenic non-epileptic seizures (PNES) are a type of functional neurological disorder (FND) characterized by seizure-like symptoms without EEG correlates. PNES is severely debilitating to children and families, making this a significant clinical and societal burden. Recent research has revealed catastrophic symptom expectations and sense of control as potential targets for pediatric PNES treatment. Children with PNES have greater catastrophic symptom expectations, or the interpretation of physical sensations as injurious, intense and disturbing, than their siblings and peers with epilepsy. Catastrophic symptom expectations such as these have been found to actually induce the expected symptom. Also, children do not have a sense of control over PNES symptoms, indicating that children perceive PNES to be involuntary and uncontrollable. In adults, studies using cognitive behavioral therapy or SSRIs to target mood and anxiety have demonstrated no significant reduction in PNES compared to control conditions. In a different cognitive behavioral approach, the aim of this study is to assess sense of control and catastrophic symptom expectations as treatment targets of Retraining and Control Therapy (ReACT), a novel cognitive behavioral treatment for pediatric PNES developed by the PI. Our recently published RCT demonstrated a significant decrease in PNES frequency after ReACT, and increased sense of control was significantly related to reduced PNES frequency in children with PNES. In the R61 phase, nine to 18-year olds diagnosed with PNES will engage in 12 sessions of ReACT. Sense of control over actions will be measured by the magic and turbulence task, and catastrophic symptom expectations will be measured by cortisol response to the cold pressor task 7 days before treatment and 7 days after the 8th and 12th treatment sessions (to evaluate treatment dose). PNES outcomes will be measured by number of PNES in the 30 days before and after treatment. The study will proceed to the R33 phase if Go criteria are met (Cohen's d effect size ≥ 0.5) for engagement of one of the targets. For the R33, children will be randomized to either ReACT or an active therapy (supportive therapy), and outcomes will be measured 7 days before and after treatment and 6 months after treatment. The replication of target engagement will be assessed as compared to supportive therapy, and the extent to which the change in the targets is associated with change in PNES frequency will be determined. The preliminary signal of efficacy for ReACT on PNES will be evaluated to prepare for a larger multicenter RCT assessing the efficacy of ReACT on pediatric PNES.