Neural signatures of dynamic threat processing in youth

项目摘要 焦虑症几乎是我们面临的最麻烦的公共卫生问题之首， 每年数十亿美元。同样重要的是，许多人的生命被令人衰弱的痛苦所摧毁， 慢性回避，导致生活质量下降，失去潜力和紧急共病状况（例如， 抑郁症）。慢性、异常升高的威胁处理是病理生理学中的关键， 焦虑症的维持。到目前为止，关于焦虑中威胁处理的研究一直使用被动观察， 静态威胁刺激。然而，现实生活中的威胁并不是静态的，威胁的性质会随着时间的推移而变化。我们 我建议用一个动态威胁处理游戏来弥补现存研究的这一重要局限性（ Boom）。Boom旨在评估神经系统对动态变化的威胁的反应， 有焦虑和无焦虑的年轻人。繁荣是发展敏感，从事青年， 校准用于检测威胁处理中的个体差异。采用儿童友好的卡通式 图像，游戏评估了年轻人对连续的，自然演变的威胁环境的处理： 潜在的威胁，然后是直接或间接的严重威胁的检测，并有机会重新评估间接威胁， 不需要立即作出反应的威胁。我们提出了一种多方法（EEG，行为和多方法）， 信息提供者表型）研究，以评估Boom评估10- 14岁儿童的有效性和可靠性。 20岁儿童对动态变化的威胁环境的神经反应，开始解开连续的 社区和临床转诊青年之间威胁处理级联的阶段， 焦虑的严重性繁荣提供了一个独特的透镜到动态威胁处理中断的焦虑， 现有的评估无法衡量。然而，建立繁荣的可靠性和有效性是一个 关键的第一步。在心理测量验证之后，我们预计繁荣将产生重要的见解， 机制有助于发展和维持焦虑症。这项工作可以告知 设计针对焦虑症的新型或个性化干预措施，以动态威胁处理为目标 干扰这项研究将提供定量的，基于大脑发育的生物标志物，用于两个关键的 研究领域标准（RDoC）负效价结构，潜在威胁和急性威胁。此外，委员会认为， 该项目与NIMH战略规划战略1.1保持一致，其中包括识别和验证 新的分析方法来量化大脑回路活动的变化。

PROJECT SUMMARY Anxiety disorders are near the top of the list of the most troublesome public health concerns we face, costing billions of dollars annually. Equally important are the many individual lives devastated by debilitating distress and chronic avoidance, leading to diminished quality of life, lost potential and emergent comorbid conditions (e.g. depression). Chronic, abnormally heightened threat processing is a linchpin in the pathophysiology and maintenance of anxiety disorders. Research to date on threat processing in anxiety has used passive viewing of static threat stimuli. However, real-life threats are not static—the nature of threats changes over time. We propose to remedy this important limitation of the extant research with a dynamic threat processing game (the Boom). The Boom is designed to assess a profile of neural responses to dynamically evolving threats among youth with and without elevated anxiety. The Boom is developmentally sensitive, engaging for youth, and calibrated for the detection of individual differences in threat processing. Employing child-friendly cartoon-like images, 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. We propose a multi-method (EEG, behavior, and multi- informant phenotyping) study to evaluate the validity and reliability of the Boom for assessing 10- to 14- year-olds’ neural responses to dynamically evolving threat contexts, to begin to unpack successive stages in a threat processing cascade among community and clinically-referred youth with varying anxiety severity. The Boom provides a unique lens into dynamic threat processing disruptions in anxiety that are not measured by existing assessments. However, establishing the reliability and validity of the Boom is a critical first step. Following psychometric validation, we expect the Boom will yield important insights into mechanisms contributing to the development and maintenance of anxiety disorders. This work may inform the design of novel or personalized interventions for anxiety disorders targeting dynamic threat processing disruptions. 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. Moreover, this project is well-aligned with the NIMH Strategic Plan Strategy 1.1, which includes identification and validation of novel assays to quantify changes in the activity of brain circuits.