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

基本信息

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
项目类别：
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

项目摘要

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）是对创伤事件的极端和持续的不良适应反应。 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。两个症状簇 - 重新体验症状，包括侵入性记忆和思想，有时是由环境提示触发的，以及促进的症状，其特征是对威胁的滋补状态和对环境的主动监测，以维持有效的职业和社交功能。具有PTSD的个体很容易重新体验各种环境中的创伤，并响应各种线索，这些线索通常与最初的创伤事件不同。恐惧的概括和情境化范例提供了测试功能性大脑区域中假设的变化和PTSD中的连通性改变的模型，而PTSD的连通性偏向于将环境中的线索解释为相关的创伤，从而保持了重新体验的症状。高音症状的特征是持续的威胁监测。捕食者压力模型检查了对即将发生威胁的警惕和主动应对响应，这对于测试由威胁性环境创造的多个竞争需求的系统的变化很有用。我们建议测试一个神经回路模型，构成了PTSD的重新体验和超出症症状的基础。网络模型的功能组成部分包括由杏仁核，延长的杏仁核/腹侧纹状体，岛状和腹侧pFC组成的威胁系统，以及由河马，前扣带动式，背部纹状体，pororsomedial pfc pfc，Pfc，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，Pfc，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，PFC，精致。为了深入了解PTSD的重新体验和过度阳极症状的发病机理，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式，这些范式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相关功能障碍。这些任务将在退伍军人中进行，PTSD从中东的9/11后运营返回并暴露于战斗的控制措施，而大脑网络关系将与当前的PTSD症状相关。在PTSD的发病机理中获得的见解将为开发针对症状的未来治疗干预措施奠定基础。