Fear learning and reconsolidation after trauma exposure a computational approach

描述（由申请人提供）：战斗和其他创伤暴露的情感后遗症主要产生五个核心症状群：重新体验，逃避，情绪麻木/烦躁不安，烦躁不安唤醒和焦虑唤醒。这种表征创伤相关症状的方法本质上是跨诊断和维度的，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的诊断。尽管这些因素构成了创伤性精神病理学的良好表型模型，但人们对这些维度背后的神经回路知之甚少，也不知道创伤性精神病理学的特征，如恐惧学习，是如何与这种异质性表型的组成方面相关联的。基于可观察行为和神经生物学测量的维度，阐明创伤性精神病理表型特征之间的联系，可以揭示个体差异，促进个性化的临床干预。我们建议在创伤暴露的个体中使用两种高度有效的方案来评估这些关联：逆转学习和检索-消失。在逆向学习中，参与者首先经历恐惧习得，当他们遇到两个刺激时，他们知道其中一个以威胁结束，而另一个没有。在随后的逆转阶段，参与者了解到先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再激活之后，即在再巩固期间，允许恐惧记忆与在消退中学习到的安全信息更新，这被证明可以成功地防止旧的恐惧记忆重新出现。这些范式为研究恐惧和安全学习和记忆修正的神经回路和心理生理学，以及它们与涉及威胁、唤醒和调节系统以及损失的负效价系统的表型测量的关系提供了一个独特的平台。在本研究中，我们旨在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，以及它们与表现为跨诊断和全维度相关精神症状的退伍军人的应激相关精神病理的关联。

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.