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、烦躁唤起和焦虑唤起。这种表征创伤相关症状的方法本质上是跨诊断和多维的，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，而不管 DSM 诊断如何。尽管这些因素构成了创伤诱发的精神病理学的合理表型模型，但人们对这些维度背后的神经回路或创伤相关精神病理学的特征（例如恐惧学习）如何与这种异质表型的组成方面相关联知之甚少。基于可观察行为和神经生物学测量的维度，阐明创伤诱发的精神病理学表型特征之间的联系，可以揭示个体差异并促进针对个人的临床干预措施。我们建议使用两种高度验证的方案来评估遭受创伤的个体的这些关联：逆转学习和检索-消退。在逆向学习中，参与者首先经历恐惧习得，他们遇到两种刺激，并了解到其中一种刺激以威胁终止，而另一种则不会。在随后的逆转阶段，参与者了解到以前安全的刺激现在可以预测威胁，而令人恐惧的刺激现在是安全的。在检索-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，允许使用消退中学到的安全信息更新恐惧记忆，这被证明可以成功防止旧的恐惧记忆重新出现。这些范式提供了一个独特的平台来研究恐惧和安全学习和记忆修改的神经回路和心理生理学，及其与威胁、唤醒和调节系统以及损失所涉及的负价系统表型测量的关系。在拟议的研究中，我们的目的是评估控制恐惧和安全学习和记忆的神经、心理生理和计算机制，以及它们与压力相关的精神病理学的关联，如表现出跨诊断和全维度相关精神症状的退伍军人所表达的。