Anxiety disorders are the most prevalent childhood psychiatric disorders, impacting up to one third of youth. Pediatric anxiety disorders are highly impairing and, when not effectively addressed in childhood, persist across the lifespan and predict the onset of additional psychiatric disorders. Up to 50% of youth who receive the current first-line psychosocial treatment for pediatric anxiety do not sufficiently improve, highlighting the urgent need to improve treatment response rates. Prior research underscores the critical role of parents in supporting children’s fear regulation. Across species, parental presence is associated with alterations in key corticolimbic circuitry associated with fear regulation. In healthy youth, parental modulation of corticolimbic circuitry is in turn linked with reductions in anxiety. However, youth with anxiety disorders may be at risk for becoming overly reliant on parents for fear reduction. The vast majority of anxious youth (90%) report relying on their parent to help regulate their anxiety, and 97% of parents of youth with anxious children report accommodating their child’s anxiety by engaging in behaviors to reduce their child’s distress. Although accommodation reduces children’s anxiety in the short-term, it contributes to the maintenance and worsening of anxiety in the long-term. Supportive Parenting for Anxious Childhood Emotions (SPACE) offers an entirely parent-based alternative to traditional child-focused treatment that directly addresses parental accommodation of anxiety and targets parental modulation of their child’s medial prefrontal cortex activation to fearful stimuli. While SPACE has established efficacy, it is unlikely to be equally effective for all families, and questions remain regarding which families are likely to benefit most from this targeted intervention. The current multimodal study aims to identify specific pre-treatment predictors of the efficacy of SPACE as a step towards personalized treatment for pediatric anxiety disorders. A well-characterized sample of children with anxiety disorders (n=212, ages 6-12 years) completed an fMRI paradigm assessing youth’s neural reactivity to fearful face stimuli in the presence versus absence of a parent. A subset of families was then randomized to complete 12 sessions of SPACE (n=106) as part of an ongoing R61/R33-funded trial. Aim 1 will use a whole-brain approach to identify neural mechanisms related to parental accommodation of youth’s anxiety pre-treatment. Aim 2 will examine how pre-treatment individual differences in these neural and behavioral factors relate to changes in anxiety symptoms following SPACE. Finally, Aim 3 will use connectome-based predictive modeling to predict the efficacy of SPACE based on pre-treatment patterns of task-based functional connectivity. This study has important implications for improving our mechanistic and clinical understanding of family-level factors involved in anxiety. The results of this study could ...