Neural and Computational Processing of Naturalistic Threat in PTSD

项目摘要 创伤后应激障碍（PTSD），一种以异常的 对威胁刺激的反应，是一个主要的公共卫生问题，与显著的发病率和死亡率相关， 尤其是在退伍军人中。PTSD的唯一有效疗法（即，暴露疗法）创建 新的安全应对措施，与有问题的威胁应对措施竞争，但不会改变这些措施。 此外，没有确凿的证据支持精神药理学干预治疗创伤后应激障碍， 这进一步突出了对这种疾病的神经生物学知识的缺乏。例如，尽管 一般人群和退伍军人人群中创伤暴露的患病率， 决定随后精神病理学的风险和恢复力的改变是未知的。实验室模型 经常被用来研究PTSD中的威胁记忆处理-然而，这些模型消除了 这种生动的多重刺激通常会引发创伤后应激障碍的异常反应。因此，我们对创伤后应激障碍的理解 可能受到实验室威胁模型和自然威胁刺激之间的差距的限制。的理解 PTSD患者对自然主义威胁刺激的异常反应背后的精确神经生物学损伤 将支持超越掩盖症状的治疗，针对根本问题，并为治愈铺平道路。 干预措施。目前的建议旨在定义与创伤后应激障碍有关的失调神经回路 曾在伊拉克或阿富汗服役的美国退伍军人人群中的症状严重程度。我们将利用新的 开发了多变量功能磁共振成像（fMRI）技术（即，多变量模式 分析; MVPA），以确定在自然主义威胁暴露期间的大脑活动的动态模式。通过监测 神经表征的动态，自然的刺激，我们将确定是否大脑差异 在创伤后应激障碍中处理自然主义威胁刺激这是朝着确定异常威胁的根本原因迈出的一步 反应，因为威胁性刺激的异常神经表征可能必然导致紊乱 对这些失调的表征的生理反应。由于创伤后应激障碍的异常威胁反应 由外部环境中的威胁性线索以及内部重新生活过去的消极因素引发 根据记忆，本提案将评估和量化两种情况。它将评估神经处理 通过量化由战斗电影引起的神经表征的稳定性， 该提案还将通过量化个人创伤记忆的稳定性来评估神经处理 在自传体记忆的反复激活过程中的神经表征。该项目将 加强我们对威胁刺激是否以及如何在PTSD中表现出差异的理解， 促进治疗方案的发展，超越掩盖PTSD的症状，并针对 潜在的认知障碍

Project Summary Post-traumatic stress disorder (PTSD), a debilitating psychological disorder characterized by aberrant responses to threat stimuli, is a major public health concern associated with significant morbidity and mortality, especially within the veteran population. The only effective therapies for PTSD (i.e., exposure therapies) create new safety responses that compete with and mask—but do not alter—the problematic threat responses. Additionally, there is no conclusive evidence supporting psychopharmacological interventions to treat PTSD, which further highlights a lack of knowledge of the neurobiology of the disorder. For example, despite the prevalence of trauma exposure in both the general and veteran populations, the specific susceptibilities or alterations that determine risk and resilience for ensuing psychopathology are unknown. Laboratory models are frequently used to study threat memory processing in PTSD—however, these models erase the nuance of the vivid, multiplex stimuli that typically trigger aberrant responding in PTSD. Thus, our understanding of PTSD may be limited by the gap between laboratory models of threat and naturalistic threat stimuli. An understanding of the precise neurobiological impairment underlying aberrant responses to naturalistic threat stimuli in PTSD will support therapies that go beyond masking symptoms, target the root issue, and pave the way for curative interventions. The present proposal aims to define the dysregulated neural circuits that relate to PTSD symptom severity in a population of American veterans who served in Iraq or Afghanistan. We will utilize newly developed multivariate functional magnetic resonance imaging (fMRI) techniques (i.e., multivariate pattern analyses; MVPA) to identify dynamic patterns of brain activity during naturalistic threat exposure. By monitoring neural representations of dynamic, naturalistic stimuli, we will determine whether the brain differentially processes naturalistic threat stimuli in PTSD. This is a step toward identifying the root cause of aberrant threat responses, as aberrant neural representations of threatening stimuli may necessarily lead to disordered physiological responses to those dysregulated representations. Since abnormal threat responses in PTSD are triggered both by threatening cues in the external environment as well as internally re-living past negative memories, the present proposal will evaluate and quantify two scenarios. It will evaluate the neural processing of aversive, naturalistic stimuli by quantifying the stability of neural representations elicited by a combat movie. The proposal will also evaluate the neural processing of personal trauma memories by quantifying the stability of neural representations during repeated reactivations of autobiographical memories. This project will enhance our understanding of whether and how threat stimuli are differentially represented in PTSD and facilitate development of treatment options that go beyond masking the symptoms of PTSD and target the underlying cognitive impairment.