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

项目摘要 儿童期的焦虑往往会使人衰弱，这一点特别令人担忧，因为纵向研究表明， 从童年到成年早期，儿童的功能会持续下降。焦虑症就是其中之一 最常见的儿童心理健康障碍，并导致随后的生活质量下降， 增加了发生共病的可能性。异常升高的威胁处理是 焦虑症的病理生理学和维持。虽然已经做出了大量努力， 了解静态威胁刺激的被动威胁处理的潜在机制，很少有研究 一直专注于现实威胁的动态威胁处理，而现实威胁很少是静态的，而是动态的 并且随着时间的推移不断变化。克劳利博士最近的研究旨在弥合这一知识差距， 目前的研究。他的实验室最近设计了一款动态威胁处理游戏，名为“炸弹”。的 炸弹的目的是评估一个更生态有效的档案神经反应的动态演变 焦虑的年轻人的威胁。炸弹是从事青年，发展敏感，并校准为 在动态威胁处理中检测个体差异。游戏评估了年轻人对 连续、自然演变的威胁环境：警惕潜在威胁，然后检测直接或 间接的严重威胁，以及重新评估不需要立即采取行动的间接威胁的机会。 反应当前应用程序的总体目标是在焦虑和非焦虑状态下检查炸弹 青年利用多方法方法，整合一些生物生理反应， 行为报告（即，EEG、眼动追踪、瞳孔测量、行为和多信息者表型）。我 目的建立可靠有效的焦虑动态演变过程的生物标志物， 威胁，对威胁的注意力偏见，以及这些生物标志物如何相互关联， 焦虑和不焦虑的年轻人这项研究将通过评估10至14岁的青少年对炸弹的反应来评估炸弹。 神经反应动态演变的威胁环境，并开始开始解开连续的阶段， a threat威胁processing加工cascade级联and attention注意bias偏见in youth青年anxiety焦虑.预计炸弹将提供 对生物标志物的重要和必要的见解有助于发展和收购， 焦虑症的维持。这项工作的目的是提供未来的应用，通知设计 针对焦虑症的新型或个性化干预措施，目标是动态威胁处理中断， 注意偏向这项研究将提供定量的，发育知情的大脑生物标志物， 两个关键的研究领域标准（RDoC）负效价结构：潜在威胁和急性 威胁目前的建议是根据NIMH战略计划战略1.1构建的， 包括识别和验证新的测定以量化脑回路活动的变化。

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.