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

项目总结 童年焦虑通常使人虚弱，鉴于纵向研究表明，这一点尤其令人担忧 从儿童到成年早期，儿童的功能持续下降。焦虑症是一种 最常见的儿童心理健康障碍，并导致随后的生活质量下降和 罹患合并症的可能性增加。异常升高的威胁处理是关键 焦虑症的病理生理学和维持。虽然已经在以下方面做出了大量努力 了解静态威胁刺激的被动威胁加工的潜在机制的研究很少 我专注于现实生活中威胁的动态威胁处理，这些威胁很少是静态的；相反，威胁是动态的 并随着时间的推移而不断变化。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名为“炸弹”的动态威胁处理游戏。这个 BUMP的设计是为了评估对动态进化的神经反应的更生态有效的轮廓 焦虑的年轻人中的威胁。这枚炸弹吸引了年轻人，对发展敏感，并针对 在动态威胁处理中检测个体差异。这个游戏评估了青少年对 连续的、自然演变的威胁背景：对潜在威胁保持警惕，然后检测到直接或 间接严重威胁，以及重新评估不需要立即采取行动的间接威胁的机会 回应。当前应用程序的总体目标是在焦虑和非焦虑的情况下检查炸弹 青年利用多方法方法整合了许多生物生理反应和 行为报告(即脑电、眼球跟踪、瞳孔测量、行为和多信息者表型)。我 目的建立可靠、有效的焦虑生物标志物，研究焦虑的动态演变过程。 威胁、对威胁的注意偏向，以及这些生物标记物如何相互关联，并在 焦虑和不焦虑的年轻人。这项研究将通过评估10至14岁儿童的 神经对动态演变的威胁环境的反应，并开始拆解连续的阶段 青少年焦虑中的威胁加工级联效应和注意偏向。预计这枚炸弹将提供 对有助于开发和收购的生物标志物的重要和基本的见解 焦虑症的维持。这项工作旨在通过通知设计来提供未来的应用 针对焦虑症的新颖或个性化干预措施，目标是动态威胁处理中断和 注意力偏向。这项研究将提供基于大脑发育信息的定量生物标记物，用于 两个关键的研究领域标准(RDoC)负价结构：潜在威胁和急性 威胁。目前的提议是为了与NIMH战略计划战略1.1保持一致，即 包括确定和验证量化大脑回路活动变化的新分析方法。

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.