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）是一种对创伤性事件的极端和持续的适应不良反应。PTSD是受影响个体的心理健康发病率和功能丧失的主要原因。两种症状群--重新体验症状，包括侵入性记忆和想法，有时由环境线索触发，以及过度觉醒症状，其特征是紧张的关注状态和对环境的积极监测--特别不利于维持有效的职业和社会功能。患有PTSD的个体倾向于在各种环境中重新经历创伤，并对通常不同于最初创伤事件的各种线索做出反应。恐惧泛化和情境化范式提供了模型来测试PTSD中功能性脑区和连接性的假设改变，PTSD偏向于将环境中的线索解释为创伤相关，从而维持重新经历的症状。过度觉醒症状的特征是持续的威胁监测。一个捕食者压力模型，检查警惕和积极应对迫在眉睫的威胁的反应，是有用的，以测试系统的变化，管理多个，竞争的需求所创造的威胁环境。我们建议测试一个神经回路模型，该模型构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、扩展杏仁核/腹侧纹状体、海马和腹内侧PFC组成的威胁警报系统，以及由海马、前扣带回、背侧纹状体、背内侧PFC、楔前叶和腹外侧PFC组成的威胁评估系统。为了深入了解PTSD的再体验和过度唤醒症状的发病机制，我们已经开发了一系列用于功能磁共振成像设置的恐惧学习和基于威胁的唤醒的交互范例，其包含计算机游戏和虚拟现实的特征，以识别所提出的大脑网络内的连接模式中的相关功能障碍。这些任务将在从中东9/11后行动返回的创伤后应激障碍退伍军人和战斗暴露对照中进行，大脑网络关系将与当前的创伤后应激障碍症状相关。对PTSD发病机制的深入了解将为开发针对症状的未来治疗干预奠定基础。

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.