Neural Substrates of Emotion Processing and Cognitive Control Over Emotion in Youth Anxiety: An RDoC-Informed Study Across the Clinical to Nonclinical Continuum of Severity.

ABSTRACT

OBJECTIVE: Clinically anxious youth are hypervigilant to emotional stimuli and display difficulty shifting attention from emotional to nonemotional stimuli, suggesting impairments in cognitive control over emotion. However, it is unknown whether the neural substrates of such biases vary across the clinical-to-nonclinical range of anxiety or by age. METHOD: Youth aged 7 to 17 years with clinical anxiety (n = 119) or without an anxiety diagnosis (n = 41) matched emotional faces or matched shapes flanked by emotional face distractors during magnetic resonance imaging, probing emotion processing and cognitive control over emotion, respectively. Building from the National Institute of Mental Health Research Domain Criteria (RDoC) framework, clinically anxious youth were sampled across diagnostic categories, and non-clinically affected youth were sampled across minimal-to-subclinical severity. RESULTS: Across both conditions, anxiety severity was associated with hyperactivation in the right inferior parietal lobe, a substrate of hypervigilance. Brain-anxiety associations were also differentiated by attentional state; anxiety severity was associated with greater left ventrolateral prefrontal cortex activation during emotion processing (face matching) and greater activation in the left posterior superior temporal sulcus and temporoparietal junction (and slower responses) during cognitive control over emotion (shape matching). Age also moderated associations between anxiety and cognitive control over emotion, such that anxiety was associated with greater right thalamus and bilateral posterior cingulate cortex activation for children at younger and mean ages, but not for older youth. CONCLUSION: Aberrant function in brain regions implicated in stimulus-driven attention to emotional distractors may contribute to anxiety in youth. Results support the potential utility of attention modulation interventions for anxiety that are tailored to developmental stage. CLINICAL TRIAL REGISTRATION INFORMATION Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety; https//clinicaltrials.gov; NCT02810171.