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.

Plain language summary

Preferential attention to threat, an adaptive mechanism for detecting danger, is exaggerated in clinically anxious youth. This study included 150 youth aged 7 to 17 years spanning the clinical-nonclinical range of anxiety to examine the effects of anxiety and age on markers of emotion processing and cognitive control over emotion while undergoing MRI scanning. The authors found that more severe anxiety was associated with greater activation in the left ventrolateral prefrontal cortex, a region supporting cognitive control over emotion, which may prevent anxiety-related slowing of response times. Conversely, when participants were prompted to ignore emotional faces, anxiety severity was associated with slower performance and greater activation of the ventral attention network, suggesting greater stimulus-driven attention to emotional distractors. Age moderated associations between anxiety and brain activity during cognitive control over emotion, supporting the potential utility of tailoring interventions for anxiety.

Clinical Trial Registration Information

Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety; https://clinicaltrials.gov; NCT02810171.