The identification of novel biomarkers related to potential and acute threats: Dynamically evolving threat processing and attention bias in youth with anxiety

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PROJECT SUMMARY Childhood anxiety is often debilitating, which is particularly concerning given that longitudinal research suggests that a child’s functioning continues to decrease from childhood into early adulthood. Anxiety disorders are one of the most common childhood mental health disorders and lead to subsequent diminished quality of life and an increased likelihood of developing comorbid conditions. Abnormally elevated threat processing is the crux of the pathophysiology and maintenance of anxiety disorders. While there have been substantial efforts at understanding the underlying mechanisms of passive threat processing of static threat stimuli, very few studies have focused on dynamic threat processing of real-life threats which are rarely static; rather, threats are dynamic and constantly changing over time. Dr. Crowley’s recent research has aimed at bridging this knowledge gap in the current research. His lab has recently designed a dynamic threat processing game called the “Bomb.” The Bomb was designed to assess a more ecologically valid profile of neural responses to dynamically evolving threats among anxious youth. The Bomb is engaging for youth, developmentally sensitive, and calibrated for the detection of individual differences in dynamic threat processing. The game assesses youths’ processing of successive, naturally evolving threat contexts: vigilance for potential threats, followed by detection of direct or indirect acute threats, and an opportunity to reappraise indirect threats that do not require an immediate response. The overall goal of the current application is to examine the Bomb in anxious and non-anxious youth utilizing a multi-method approach integrating a number of biophysiological responses and behavioral reports (i.e., EEG, eye-tracking, pupillometry, behavior, and multi-informant phenotyping). I aim to establish reliable and valid biomarkers of anxiety in the processing of dynamically evolving threats, attention bias towards threat, and how these biomarkers relate to one another, and differ among anxious and non-anxious youth. The study will evaluate the Bomb by assessing 10- to 14-year-olds’ neural responses to dynamically evolving threat contexts, and to begin to unpack successive stages in a threat processing cascade and attention bias in youth anxiety. It is expected that the Bomb will provide important and essential insights into biomarkers contributing to the development and acquisition and maintenance of anxiety disorders. This work was designed to provide future application by informing the design of novel or personalized interventions for anxiety disorders targeting dynamic threat processing disruptions and attention bias. This study will deliver quantitative, developmentally informed brain-based biomarkers, for two key Research Domain Criteria (RDoC) negative valence constructs: Potential Threat and Acute Threat. The current proposal was constructed to be in line with the NIMH Strategic Plan Strategy 1.1 that includes identification and validation of novel assays to quantify changes in the activity of brain circuits.