Neuroanatomy of Anticipation in Anxiety Disorders

描述（由申请人提供）：焦虑和情绪障碍是使人衰弱的疾病，会造成巨大的个人痛苦，并产生很高的社会和经济负担。这些障碍的一个中心特征是对潜在的令人厌恶的结果的过度预期。虽然预期对于成功准备和适应厌恶事件至关重要，但该系统的功能障碍会显著干扰社会和职业功能。通过研究这种预期系统的神经生物学，与预期的特定功能相关的神经区域，如自主处理，负面影响和行为退缩，可以通过心理或生物治疗来识别和靶向。此外，拟议中的事件相关功能性磁共振成像（fMRI）研究利用了预期的两个关键特征：对未来的不确定性和无法控制它。在先前研究的基础上，使用一个预测厌恶图片的警告符号和另一个预测中性的预测范式，第一项研究将操纵不确定性（即，图片内容的可预测性），包括一个模糊的警告符号，后面跟着令人厌恶的或中性的图片。第二项研究将通过包括行为反应可以缩短图片持续时间的条件来操纵不可控性。在前两项研究中，将在健康志愿者中测试不确定性和不可控性对所提出的厌恶预期模型中关键神经区域的影响。在最后的研究中，这两种模式将用于相关的临床人群广泛性焦虑症，社交焦虑症（社交恐惧症），和重性抑郁症，以确定前2项研究中确定的规范性回路如何在焦虑和情绪障碍中异常。主要的预测是，焦虑症有一个神经信号，对应于潜在的厌恶结果所涉及的预期过程中的一般功能障碍，特别是在不确定和不可控的情况下。总之，这种应用对预测即将发生的危险的能力的强调是研究情感障碍的一种新方法，该方法面向关于健康防御机制的神经生物学的基本知识（例如，预期导致适应性反应）以及了解该系统中的功能障碍如何发生。

DESCRIPTION (provided by applicant): Anxiety and mood disorders are debilitating conditions that cause tremendous personal suffering and engender a high societal and economic burden. A central feature of these disorders is excessive anticipation of potentially aversive outcomes. While anticipation is critical for successful preparation and adaptation to aversive events, dysfunction in this system can interfere markedly with social and occupational functioning. By investigating the neurobiology of this anticipatory system, neural areas associated with specific functions of anticipation, such as autonomic processing, negative affect, and behavioral withdrawal, can be identified and targeted by psychological or biological treatments. In addition, the proposed event-related functional magnetic resonance imaging (fMRI) studies capitalize on 2 key characteristics of anticipation: uncertainty about the future and an inability to control it. Building on prior research using an anticipation paradigm with 1 warning symbol that predicts aversive pictures and another predicting neutral, the first study will manipulate uncertainty (i.e., predictability of picture content) by including an ambiguous warning symbol that is followed by either aversive or neutral pictures. The second study will manipulate uncontrollability by including a condition in which a behavioral response can shorten picture duration. The influence of uncertainty and uncontrollability on key neural areas in the proposed model for aversive anticipation will be tested with healthy volunteers in the first 2 studies. For the final study, both paradigms will be used with relevant clinical populations-generalized anxiety disorder, social anxiety disorder (social phobia), and major depressive disorder-to determine how the normative circuitry identified in the first 2 studies is aberrant in anxiety and mood disorders. The primary prediction is that there is a neural signature for anxiety disorders that corresponds to a general dysfunction in anticipatory processes engaged by potential aversive outcomes, especially in situations of uncertainty and uncontrollability. In sum, the emphasis of this application on the capacity to anticipate impending danger is a novel approach to the study of affective disorders that is geared toward basic knowledge about the neurobiology of healthy defense mechanisms (e.g., anticipation that results in adaptive response) as well as understanding how dysfunction in this system occurs.