Currently, 50% of children do not benefit from evidence-based treatments for childhood anxiety disorders. This R61/R33 application proposes to test whether a novel entirely parent-based psychosocial intervention for childhood anxiety disorders engages amygdala-medial prefrontal cortex (mPFC) neural circuitry in the child's brain, implicated in children's reliance on parents to reduce their amygdala reactivity and anxiety; and whether changes in the target circuitry after treatment are associated with reductions in child anxiety. The R61 study will randomly assign 90 children (ages 7-10yrs) with primary anxiety disorders to one of two interventions: 1) Supportive Parenting for Anxious Childhood Emotions (SPACE), a novel completely parent- based treatment with no direct child involvement, that reduces children's anxiety by reducing parents' accommodation of their child's symptoms; or 2) Parent Educational Support (PES), a credible comparator intervention that is also entirely parent-based and controls for treatment duration and parent-therapist contact, but does not include any active modification of parental behavior. Before and after treatment, functional magnetic resonance imaging (fMRI) will be used examine children's reliance on parents to engage the target circuitry by comparing children's amygdala reactivity and mPFC connectivity in the presence of their mother and in the absence of their mother. We expect SPACE to reduce child reliance on parental presence to reduce amygdala reactivity, significantly more than PES. If this hypothesis is supported the R33 will be performed. The R33 will randomly assign 136 children (7-10yrs) with primary anxiety disorders to one of two interventions: 1) Parents participate in SPACE; or 2) Children receive cognitive-behavioral therapy (CBT), a standard of care treatment of known efficacy. We will use before and after fMRI and multi-informant/multi-modal child anxiety evaluations. We expect SPACE to reduce child reliance on parental presence to reduce amygdala reactivity, significantly more than CBT; We expect target engagement in SPACE to be associated with child anxiety symptom reduction; We expect SPACE will be feasible to deliver and acceptable to children and parents. This study is innovative in several ways and has the potential for large clinical and scientific impact. It is the first study to examine the impact of a psychosocial intervention on the neural circuitry of children with anxiety disorders, and the first study to examine the effects of an exclusively parent-only intervention with no child-therapist contact, on child brain circuitry. It will provide insight into the neurobiology of children's dependence on attachment figures for anxiety reduction, a process that contributes to the impairment and costs associated with childhood anxiety disorders. As many children are unable or unwilling to participate in therapy, results supporting the promise of SPACE as an effective way to reduce childhood a...