Brain Systems for Fear Generalization and Threat Processing in PTSD

描述(由申请人提供)： 创伤后应激障碍(PTSD)是一种对创伤事件的极端和持续的适应不良反应。创伤后应激障碍是受影响个人心理健康发病率和功能丧失的主要原因。有两组症状--重新体验的症状，包括侵入性记忆和思想，有时由环境线索触发；以及过度唤醒症状，其特征是紧张的担忧状态和积极监测环境中的威胁--对维持有效的职业和社会功能特别不利。患有创伤后应激障碍的人容易在各种环境中重新经历创伤，并对各种通常与最初的创伤事件不同的线索做出反应。恐惧泛化和情境化范式提供了模型来测试创伤后应激障碍中大脑功能区和连接性的假设变化，这些变化偏向于将环境中的线索解释为与创伤相关，从而维持再次体验的症状。高度觉醒症状的特征是持续的威胁监测。捕食者压力模型考察了对迫在眉睫的威胁的警觉和积极应对反应，对于测试管理由威胁环境产生的多个相互竞争的需求的系统中的变化很有用。我们建议测试一种神经回路模型，该模型形成了创伤后应激障碍的再体验和过度觉醒症状的基础。该网络模型的功能组件包括由杏仁核、扩展的杏仁核/腹侧纹状体、岛叶和腹内侧PFC组成的威胁警报系统，以及由海马体、前扣带回、背侧纹状体、背内侧PFC、楔前核和腹外侧PFC组成的威胁评估系统。为了深入了解创伤后应激障碍的再体验和高唤醒症状的发病机制，我们为fMRI环境开发了一系列恐惧学习和基于威胁的唤醒的互动范例，其中包含计算机游戏和虚拟现实的特征，以确定拟议的大脑网络中连接模式的相关功能障碍。这些任务将在退伍军人中进行，这些退伍军人从中东9/11事件后的行动中返回，并接受战斗暴露的对照，大脑网络关系将与当前的创伤后应激障碍症状相关。对创伤后应激障碍发病机制的洞察将为开发未来针对症状的治疗干预措施奠定基础。

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) is an extreme and sustained maladaptive response to traumatic events. PTSD is a major cause of mental health morbidity and loss of function in affected individuals. Two symptom clusters - re-experiencing symptoms, which include intrusive memories and thoughts, sometimes triggered by environmental cues, and hyperarousal symptoms, characterized by a tonic state of concern and active monitoring of the environment for threat - are particularly debilitating for maintaining effective occupational and social functioning. Individuals with PTSD are prone to re-experience the trauma in a variety of settings and in response to a variety of cues that often differ from the initial traumatic event. Fear generalization and contextualization paradigms provide models to test hypothesized alterations in functional brain regions and connectivity in PTSD that is biased to interpreting cues in the environment as trauma relevant, thus maintaining re-experiencing symptoms. Hyperarousal symptoms are characterized by constant threat monitoring. A predator stress model, which examines vigilance and active coping responses to imminent threats, is useful to test changes in systems that manage multiple, competing demands created by a threatening environment. We propose to test a neural circuit model that forms the basis of re-experiencing and hyperarousal symptoms of PTSD. The functional components of the network model include a threat-alerting system that consists of the amygdala, extended amygdala/ventral striatum, insula, and ventromedial PFC, and a threat-assessing system that consists of hippocampus, anterior cingulate, dorsal striatum, dorsomedial PFC, precuneus, and ventrolateral PFC. To gain insight into the pathogenesis of the re-experiencing and hyperarousal symptoms of PTSD, we have developed a series of interactive paradigms of fear learning and threat-based arousal for the fMRI setting that contain features of computer gaming and virtual reality to identify the relevant dysfunction in connectivity patterns within the proposed brain network. These tasks will be conducted in Veterans with PTSD returning from post-9/11 operations in the Middle East and combat-exposed controls, and brain network relationships will be correlated with current PTSD symptoms. The insights gained into the pathogenesis of PTSD will lay the groundwork for developing future therapeutic interventions that are targeted to symptoms.