Brain Systems for Fear Generalization and Threat Processing in PTSD

创伤后应激障碍 (PTSD) 中恐惧泛化和威胁处理的大脑系统

• 批准号: 8811835
• 负责人: RAJENDRA A MOREY
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811835
• 关键词: Adopted; Affect; Amygdaloid structure; Animal Model; Anterior; Arousal; Brain; Brain imaging; Brain region; Cognitive; Computers; Conditioned Reflex; Conditioned Stimulus; Corpus striatum structure; Cues; Dorsal; Emotional; Environment; Experimental Models; Extinction (Psychology); Face; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Galvanic Skin Response; Goals; Health; Hippocampus (Brain); Individual; Insula of Reil; Learning; Maintenance; Memory; Mental Health; Middle East; Modeling; Monitor; Morbidity - disease rate; Occupational; Participant; Pathogenesis; Pattern; Post-Traumatic Stress Disorders; Process; Recovery; Recruitment Activity; Research; Resources; Role; Series; Social Functioning; Stimulus; Stress; Symptoms; System; Task Performances; Testing; Therapeutic Intervention; Thinking; Trauma; Ventral Striatum; Veterans; War; base; brain behavior; classical conditioning; combat; conditioned fear; conditioning; coping; experience; innovation; insight; loss of function; memory process; mind control; network models; neural circuit; neural model; neuromechanism; novel; operation; public health relevance; relating to nervous system; response; traumatic event; vigilance; virtual reality; visual motor

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.

描述（由申请人提供）： 创伤后应激障碍（PTSD）是对创伤事件的一种极端且持续的适应不良反应。创伤后应激障碍是受影响个体心理健康发病和功能丧失的主要原因。两个症状群——重新体验症状，包括侵入性记忆和思想，有时由环境线索触发，以及过度警觉症状，其特征是紧张的关注状态和主动监测环境威胁——尤其会削弱维持有效的职业和活动能力。社会功能。患有创伤后应激障碍 (PTSD) 的人很容易在各种环境中重新经历创伤，并对各种与最初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 PTSD 中功能性大脑区域和连接性的假设变化，这些变化倾向于将环境中的线索解释为与创伤相关，从而维持重新体验症状。过度警觉症状的特点是持续的威胁监控。捕食者压力模型检查对迫在眉睫的威胁的警惕性和积极应对反应，可用于测试管理由威胁环境产生的多种竞争需求的系统的变化。我们建议测试一种神经回路模型，该模型构成了创伤后应激障碍（PTSD）重新体验和过度觉醒症状的基础。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、岛叶和腹内侧 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 组成的威胁评估系统、楔前叶和腹外侧 PFC。为了深入了解 PTSD 的重新体验和过度唤醒症状的发病机制，我们为 fMRI 设置开发了一系列恐惧学习和基于威胁的唤醒的交互式范例，其中包含计算机游戏和虚拟现实的特征，以识别相关的恐惧学习和基于威胁的唤醒。所提出的大脑网络内连接模式的功能障碍。这些任务将在从 9/11 后中东行动返回的患有 PTSD 的退伍军人和暴露在战斗中的对照中进行，并且大脑网络关系将与当前的 PTSD 症状相关联。对 PTSD 发病机制的深入了解将为开发未来针对症状的治疗干预措施奠定基础。