Responding to threat: Associations between neural reactivity to and behavioral avoidance of threat in pediatric anxiety

Background: Despite broad recognition of the central role of avoidance in anxiety, a lack of specificity in its operationalization has hindered progress in understanding this clinically significant construct. The current study uses a multimodal approach to investigate how specific measures of avoidance relate to neural reactivity to threat in youth with anxiety disorders. Methods: Children with anxiety disorders (ages 6-12 years; n = 65 for primary analyses) completed laboratory task- and clinician -based measures of avoidance, as well as a functional magnetic resonance imaging task probing neural reactivity to threat. Primary analyses examined the ventral anterior insula (vAI), amygdala, and ventromedial prefrontal cortex (vmPFC). Results: Significant but distinct patterns of association with task- versus clinician -based measures of avoidance emerged. Clinician -rated avoidance was negatively associated with right and left vAI reactivity to threat, whereas laboratory -based avoidance was positively associated with right vAI reactivity to threat. Moreover, left vAI-right amygdala and bilateral vmPFC-right amygdala functional connectivity were negatively associated with clinicianrated avoidance but not laboratory -based avoidance. Limitations: These results should be considered in the context of the restricted range of our treatment -seeking sample, which limits the ability to draw conclusions about these associations across children with a broader range of symptomatology. In addition, the limited racial and ethnic diversity of our sample may limit the generalizability of findings. Conclusion: These findings mark an important step towards bridging neural findings and behavioral patterns using a multimodal approach. Advancing understanding of behavioral avoidance in pediatric anxiety may guide future treatment optimization by identifying individual -specific targets for treatment.