Common and Specific Neural Mechanisms of Perseverative Thought in Real-World Contexts

焦虑和抑郁症是最常见的精神疾病形式，是一种主要的公共健康问题。 关心有越来越多的证据表明，持续性思维（PT），定义为以自我为中心的思维， 重复的，难以控制的，是焦虑和抑郁的关键机制。忧虑和沉思是两个 PT的流行和良好表征形式，已通过实验和前瞻性研究与 焦虑和抑郁的严重程度增加，药物滥用率上升，身体健康状况恶化。 然而，对PT的潜在神经生物学知之甚少，迄今为止还没有研究表明 PT调节成功或不成功的神经机制。文献中的空白 是至关重要的，因为从PT脱离的能力受损（即，停止忧虑的能力， 反刍）被认为是一种中心机制，通过这种机制，担忧或反刍从 从正常到病态K 01的首要目标是开发和测试一种生态有效的， PT的临床信息神经生物学模型，特别强调通过以下方式确定机制 通过成功和不成功的调节，PT从健康转变为病理。使用功能性 磁共振成像（fMRI）和生态瞬时评估（EMA），拟议的研究将1） 测试关于成功和失败的机制的特定神经生物学假设 脱离PT; 2）评价三种竞争性临床来源的 PT模型（即，双因素对双因素对维度模型）;以及3）将神经生物学发现与真实的- 病理性（失调）担忧和沉思的世界经验。总的来说，这些目标将允许 迭代完善具有临床意义的规范性和病理性PT的神经生物学模型， 可以为神经生物学干预的发展奠定基础。一致的 根据研究领域标准（RDoC）的跨诊断方法，N = 70名代表 PT严重程度的全谱（低;中度;病理性）将在经历时接受fMRI，然后 试图摆脱PT（担心和沉思）。脱离接触成功将通过思考进行评估 取样.然后，患有病理性PT的一部分参与者将完成EMA方案，以索引真实世界 成功和失败的脱离PT的经验。各种数据分析方法，包括 功能和有效的连通性、混合模型和结构方程模型将用于测试 具体假设和后续探索性分析。培训计划充分利用候选人的 背景，指导团队，研究环境，为候选人提供必要的神经成像， EMA和数据分析技能，以进行拟议的研究，并启动一个成功的独立研究 一个旨在确定情绪相关精神病理学（NIMH）的神经认知机制的职业 战略目标1）为确定新的治疗目标（NIMH战略目标3）服务。

Anxiety and depressive disorders are the most prevalent forms of mental illness and are a major public health concern. There is growing evidence that perseverative thought (PT), defined as thought that is self-focused, repetitive, and difficult-to-control, is a key mechanism of anxiety and depression. Worry and rumination are two prevalent and well-characterized forms of PT that have been experimentally and prospectively linked to increased anxiety and depression severity, higher rates of substance abuse, and poorer physical health. However, little is known about the underlying neurobiology of PT, and no studies to date have characterized the neural mechanisms that underlie the successful or unsuccessful regulation of PT. This gap in the literature is of central importance because an impaired ability to disengage from PT (i.e., an ability to stop worrying and ruminating) has been proposed as a central mechanism by which worry or rumination transitions from normative to pathological. The overarching goal of this K01 is to develop and test an ecologically-valid, clinically-informed neurobiological model of PT, with a particular emphasis on identifying the mechanisms by which PT shifts from healthy to pathological through successful and unsuccessful regulation. Using functional magnetic resonance imaging (fMRI) and ecological momentary assessment (EMA), the proposed study will 1) test specific neurobiological hypotheses about the mechanisms underlying successful and failed disengagement from PT; 2) evaluate the neurobiological plausibility of three competing clinically-derived models of PT (i.e., a bifactor vs. two-factor vs. dimensional model); and 3) link neurobiological findings to real- world experiences of pathological (dysregulated) worry and rumination. Collectively, these aims will permit the iterative refinement of a clinically meaningful neurobiological model of normative and pathological PT, which can form the basis for the development of neurobiologically informed interventions. Consistent with a transdiagnostic approach informed by the Research Domains Criteria (RDoC), N = 70 adults who represent the full spectrum of PT severity (low; moderate; pathological) will undergo fMRI while experiencing and then attempting to disengage from PT (worry and rumination). Disengagement success will be assessed via thought sampling. A subset of participants with pathological PT will then complete an EMA protocol to index real-world experiences of successful and failed disengagement from PT. A variety of data analytic approaches, including functional and effective connectivity, mixed models, and structural equation modeling will be applied to test specific hypotheses and in follow-up exploratory analyses. The training plan capitalizes on the candidate's background, mentorship team, research environment to provide the candidate with the requisite neuroimaging, EMA, and data analytic skills to conduct the proposed research and launch a successful independent research career aimed at identifying the neurocognitive mechanisms of emotion-related psychopathology (NIMH Strategic Objective 1) in service of identifying new targets for treatment (NIMH Strategic Objective 3).