Fear learning and reconsolidation after trauma exposure a computational approach

创伤暴露后的恐惧学习和重新巩固——一种计算方法

• 批准号: 8802342
• 负责人: ILAN HARPAZ-ROTEM
• 金额: $ 51.7万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8802342
• 关键词: Amygdaloid structure; Anxiety; Arousal; Arousal and Regulatory Systems; Attention; Behavior; Behavioral; Characteristics; Clinical; Cognitive; Computer Simulation; Corpus striatum structure; Cues; Development; Diagnosis; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Dimensions; Discrimination; Emotional; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Functional disorder; Galvanic Skin Response; Impairment; Individual; Individual Differences; Intervention; Learning; Link; Measures; Mediating; Memory; Mental Depression; Modeling; Modification; National Institute of Mental Health; Nature; Negative Valence; Neurobiology; Outcome; Participant; Performance; Phase; Phenotype; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Protocols documentation; Psychopathology; Psychophysiology; Research; Research Domain Criteria; Retrieval; Reversal Learning; Safety; Severities; Staging; Stimulus; Stress; Symptoms; System; Testing; Training; Trauma; Update; Veterans; anxious; base; classical conditioning; combat; disease classification; dysphoria; experience; fear memory; neural circuit; neural patterning; novel strategies; prevent; public health relevance; relating to nervous system; response; sound; tool

DESCRIPTION (provided by applicant): The emotional sequelae of combat and other trauma exposure primarily give rise to five core symptom clusters: re-experiencing, avoidance, emotional numbing/dysphoria, dysphoric arousal, and anxious arousal. This approach to characterizing trauma-related symptomatology is inherently transdiagnostic and dimensional in nature and accords with the NIMH Research Domain Criteria (RDoC) project, which seeks to classify individuals with respect to unique behavioral and neural patterns irrespective of DSM diagnosis. Although these factors constitute a sound phenotypic model of trauma-induced psychopathology, little is known about the neural circuitry that underlies these dimensions or how characteristics of trauma-related psychopathology, such as fear learning, relate to component aspects of this heterogeneous phenotype. Elucidation of links between phenotypic characteristics of trauma-induced psychopathology, based on dimensions of observable behavior and neurobiological measures, could uncover individual differences and promote personally- tailored clinical interventions. We propose to assess these associations in trauma-exposed individuals using two highly validated protocols: reversal learning and retrieval-extinction. In reversal learning, participants first undergo fear acquisition where they encounter two stimuli and learn that one of them terminates with threat, whereas the other one does not. In the subsequent reversal phase, participants learn that the formerly safe stimulus now predicts threat, and the fearful one is now safe. In the retrieval-extinction paradigm, extinction training occurs after memory reactivation, i.e., during reconsolidation, allowing the updating of the fear memory with the safety information learned in extinction, which was shown to successfully prevent old fear memories from resurfacing. These paradigms provides a unique platform to investigate the neurocircuitry and psychophysiology of fear and safety learning and memory modification, and their relation to phenotypic measures of negative valence systems implicated in threat, arousal and regulatory systems, and loss. In the proposed study, we aim to evaluate the neural, psychophysiological, and computational mechanisms that govern fear and safety learning and memory, and their association to stress related psychopathology as expressed in combat veterans presenting with a transdiagnostic and full dimensional range of associated psychiatric symptoms.

描述（由申请人提供）：战斗和其他创伤暴露的情绪后遗症主要引起五个核心症状群：重新体验、回避、情绪麻木/烦躁不安、烦躁不安和焦虑不安。这种表征创伤相关神经病学的方法本质上是跨诊断和维度的，并且符合NIMH研究领域标准（RDoC）项目，该项目旨在根据独特的行为和神经模式对个体进行分类，而不考虑DSM诊断。虽然这些因素构成了一个健全的表型模型的创伤诱导的精神病理学，鲜为人知的是这些方面的神经回路，或如何创伤相关的精神病理学的特点，如恐惧学习，涉及到组件方面的异质性表型。基于可观察行为和神经生物学测量的维度，阐明创伤诱导的精神病理学的表型特征之间的联系，可以揭示个体差异并促进个性化的临床干预。我们建议使用两种高度有效的协议来评估这些协会在创伤暴露的个人：逆转学习和检索灭绝。在反向学习中，参与者首先经历恐惧获得，他们遇到两个刺激，并了解到其中一个以威胁结束，而另一个则没有。在随后的逆转阶段，参与者了解到，以前安全的刺激现在预示着威胁，而恐惧的刺激现在是安全的。在提取-消退范式中，消退训练发生在记忆重新激活之后，即，在重新巩固期间，允许用在灭绝中学到的安全信息更新恐惧记忆，这被证明可以成功地防止旧的恐惧记忆重新出现。这些范例提供了一个独特的平台，以调查恐惧和安全学习和记忆修改的神经回路和心理生理学，以及它们与负价系统的表型测量的关系，这些负价系统涉及威胁，唤醒和调节系统，以及损失。在拟议的研究中，我们的目标是评估神经，心理生理学和计算机制，管理恐惧和安全的学习和记忆，以及它们的协会与压力相关的精神病理学表现在战斗退伍军人提出了transdiagnosis和全维度范围的相关精神症状。