Using Functional Neuroimaging and Smartphone Digital Phenotyping to Understand the Emergence of Internalizing Illness

焦虑和抑郁对公共卫生造成了惊人的负担，通常在压力时期出现。 然而，潜在的机制仍然知之甚少，阻碍了改进治疗的发展。 虽然内在化疾病的病因学无疑是复杂的和多因素的，但新出现的证据促使 威胁和安全的异常神经处理独立增加的总体假设 内在化疾病的风险。这项工作表明：(A)对不确定威胁预期的高反应性 增加风险，(B)安全信号缺陷增加风险，以及(C)这些关联被放大 暴露于负性生活事件(NLE)。来自马里兰iRisk研究的档案数据提供了最佳的 为严格解决这些根本差距提供了平台。IRisk是最近完成的前瞻性纵向 这项研究的重点是种族多元化、性别平衡的新兴成年人样本，他们的风险内化程度更高。在… 登记、功能磁共振成像和成熟的威胁预测任务被用来量化对不确定的反应性 以及一定的震撼性威胁，以及安全性。对受欢迎的情绪感知的反应(与威胁相关的脸) 任务也进行了评估。使用智能手机生态瞬时评估(EMA)对 0个月、6个月、24个月和30个月的日常体验，提供前所未有的多年情绪评估 动态和第一次机会来评估威胁和安全大脑电路的现实意义。在… 还评估了每个波、情绪、症状、功能和社会支持。诊断，尺寸 在0个月、15个月和30个月时，使用黄金标准访谈评估NLEs。这些数据将 使我能够(1)理解威胁和安全迂回与内在化的出现之间的关联 症状/诊断，(2)了解它们在更多病因近端病理的出现中的作用- 促进日常生活中的情感和行为，以及(3)探索一个真正的 痛苦的威胁预测任务与广泛使用的威胁感知(情绪面孔)任务。冲击力。 内在化疾病是人类痛苦和发病的主要原因。该项目将提供一个 潜在的变革性机会，加深我们对病因学的理解，完善临床科学理论。 它将为人类和动物的力学模型的发展提供信息，并提供一个定量的 将新的生物和心理社会目标优先用于治疗发展和再利用的理由， 包括可扩展的mHealth方法。这个项目建立在我强大的计算和神经成像技能的基础上， 我在学习实施实践方面的丰富经验，以及我的初步经验 使用均线数据。它将提供一种特殊的工具，用于培训最先进的分析 方法、EMA数据收集和最佳做法、疾病内在化和研究伦理； 发展尖端研究项目、专业技能和出版记录，这是蓬勃发展所必需的 作为一名独立的临床情感神经学家。

Anxiety and depression impose a staggering burden on public health and often emerge during times of stress. Yet the underlying mechanisms remain poorly understood, thwarting the development of improved treatments. While the etiology of internalizing illness is undoubtedly complex and multifactorial, emerging evidence motivates the overarching hypothesis that aberrant neural processing of Threat and Safety independently confer increased risk for internalizing illnesses. This work suggests that: (a) hyper-reactivity to Uncertain Threat anticipation increases risk, (b) deficient Safety Signaling increases risk, and (c) these associations are magnified by exposure to Negative Life Events (NLEs). Archival data from the Maryland iRisk Study provide an optimal platform for rigorously addressing these fundamental gaps. iRisk is a recently completed prospective-longitudinal study focused on a racially diverse, sex-balanced sample of emerging adults enriched for internalizing risk. At enrollment, fMRI and a well-established Threat-anticipation task were used to quantify reactivity to Uncertain and Certain Shock-Threat, as well as Safety. Reactivity to a popular emotion-perception (‘threat-related’ faces) task was also assessed. Smartphone ecological momentary assessment (EMA) was used to intensively probe daily experience at 0, 6, 24, and 30 months, providing an unprecedented multi-year assessment of mood dynamics and a first opportunity to assess the real-world significance of Threat and Safety brain circuitry. At each wave, mood, symptoms, function, and social support were also assessed. Diagnoses, dimensional symptoms, and NLEs were assessed using gold-standard interviews at 0, 15, and 30 months. These data will enable me to (1) understand the relevance of Threat and Safety circuity to the emergence of internalizing symptoms/diagnoses, (2) understand their role in the emergence of more etiologically proximal pathology- promoting feelings and behaviors in daily life, and (3) explore the relative predictive merits of a genuinely distressing Threat-anticipation task vs. a widely used Threat-perception (emotional-faces) task. Impact. Internalizing illnesses are a leading cause of human misery and morbidity. This project would provide a potentially transformative opportunity to deepen our understanding of etiology and refine clinical science theory. It would inform the development of mechanistic models in humans and animals, and provide a quantitative rationale for prioritizing new biological and psychosocial targets for therapeutics development and repurposing, including scalable mHealth approaches. This project builds on my strong computational and neuroimaging skills, my extensive experience with practical aspects of study implementation, and my preliminary experiences working with EMA data. It would provide an exceptional vehicle for training in state-of-the-art analytic approaches, EMA data collection and best-practices, internalizing illness, and research ethics; and for developing the cutting-edge research program, professional skills, and publication record necessary to flourish as an independent clinical affective neuroscientist.