Anxiety disorders are the most common pediatric psychopathology. Despite therapeutic advances, treatment-resistance remains high, and progress towards early detection of at-risk populations has hindered. The proposed research aims to address this problem by targeting information-processing functions, specifically fear learning and extinction, in an effort to link pediatric anxiety to dysfunction in cognitive mechanisms and the underlying perturbed fear circuits. Study 1 will examine differences in fear learning, extinction and extinction recall in anxious and non-anxious children. Participants will complete a novel fear condition- extinction task in the psychophysiology laboratory. Several weeks later, they will undergo fMRI scanning probing two distinctive processes: threat memory and threat appraisal. Since such deficient extinction occurs only in symptomatic individuals, it may provide a novel therapeutic target. Study 2 will demonstrate the therapeutic relevance by examining a link between impairments in extinction learning and exposure treatment outcomes. Exposure therapy is one of the most effective interventions for anxiety disorders. This intervention relies heavily on extinction learning principles and may produce beneficial effects by altering function in ventro-medial prefrontal cortex (vmPFC). Study 2 will assess vmPFC function in anxious adolescents prior to exposure therapy. A reduced vmPFC activation pre-exposure intervention is expected to predict a stronger response to exposure intervention, thereby moderating treatment outcome. The proposed study extends innovative translational work in animals and humans by examining specific neuro-cognitive mechanisms associated with pediatric anxiety. This study will yield clinically important data, which could ultimately advance early diagnosis of children at-risk for anxiety and improve treatment.
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