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

焦虑和抑郁障碍是最常见的精神疾病形式，是一种主要的公共卫生 担忧。越来越多的证据表明，持之以恒的思维(PT)，定义为以自我为中心的思维， 重复且难以控制，是焦虑和抑郁的关键机制。忧虑和沉思是两件事 普遍的和特征良好的PT形式，已经在实验中和预期与 焦虑和抑郁的严重程度增加，药物滥用的比率更高，身体健康更差。 然而，人们对PT的潜在神经生物学知之甚少，到目前为止还没有研究表明 PT调节成功或失败的神经机制。文学中的这一空白 是至关重要的，因为脱离PT的能力受损(即停止担忧和 沉思)被认为是一种中心机制，通过这种机制，担忧或沉思从 从标准到病态。这款K01的首要目标是开发和测试一种生态有效的、 临床知情的PT神经生物学模型，特别强调通过以下方式确定机制 其中PT通过成功和不成功的调节从健康状态转变为病理状态。使用泛函 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背后机制的特定神经生物学假说 脱离PT；2)评估三个相互竞争的临床来源的神经生物学可信程度 PT的模型(即，双因素与双因素与维度模型)；以及3)将神经生物学的发现与真实的 病态(失调)焦虑和沉思的世界经验。总而言之，这些目标将允许 对具有临床意义的正常和病理性PT的神经生物学模型进行迭代改进，该模型 可以构成神经生物学知情干预措施发展的基础。与一项 研究领域标准(RDoC)提供的跨诊断方法，N=70名成人，代表 所有的PT严重程度(轻度；中度；病理性)将在经历的同时接受fMRI检查，然后 试图从PT中解脱出来(担心和沉思)。脱离接触的成功将通过思考进行评估 取样。然后，患有病理性PT的参与者子集将完成EMA协议以索引真实世界 脱离PT的成功和失败的经验。各种数据分析方法，包括 将应用功能和有效的连通性、混合模型和结构方程建模进行测试 具体的假设和后续的探索性分析。该培训计划充分利用了应聘者的 背景，指导团队，研究环境，为应聘者提供必要的神经成像， EMA，和数据分析技能，进行拟议的研究并启动成功的独立研究 旨在确定情绪相关精神病(NIMH)的神经认知机制的职业 战略目标1)，服务于确定新的治疗目标(NIMH战略目标3)。

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).