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、烦躁不安和焦虑唤醒。这种表征创伤相关症状的方法本质上是跨诊断和多维的，符合NIMH研究领域标准(RDoC)项目，该项目寻求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。尽管这些因素构成了创伤诱发精神病理学的一个良好的表型模型，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，如恐惧学习，如何与这种不同表型的组成方面联系在一起，知之甚少。基于可观察行为的维度和神经生物学测量，阐明创伤诱发精神病理学的表型特征之间的联系，可以发现个体差异，并促进个性化的临床干预。我们建议使用两种高度有效的方案来评估创伤暴露个体中的这些关联：反向学习和提取-灭绝。在反转学习中，参与者首先经历恐惧习得，在那里他们遇到两个刺激，并了解到其中一个以威胁结束，而另一个不是。在随后的逆转阶段，参与者了解到，以前安全的刺激现在预测威胁，而令人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，即在再巩固过程中，允许用在消退中学到的安全信息更新恐惧记忆，这被证明成功地防止了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改变的神经回路和心理生理学，以及它们与威胁、唤醒和调节系统以及损失中涉及的负价系统的表型测量的关系。在这项拟议的研究中，我们旨在评估支配恐惧和安全学习和记忆的神经、心理生理学和计算机制，以及它们与表现出跨诊断和全维度相关精神症状的作战退伍军人的应激相关精神病理学的关联。

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.