Neural and Computational Processing of Naturalistic Threat in PTSD

PTSD 中自然威胁的神经和计算处理

• 批准号: 10241260
• 负责人: Temidayo Orederu
• 金额: $ 4.44万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241260
• 关键词: Address; Afghanistan; American; Aversive Stimulus; Behavior; Behavior Therapy; Brain; Complex; Cues; Depressed mood; Diagnosis; Disease; Environment; Exposure to; Functional Magnetic Resonance Imaging; General Population; Human; Imaging Techniques; Impaired cognition; Impairment; Intervention; Iraq; Knowledge; Laboratories; Lead; Masks; Memory; Mental disorders; Modeling; Monitor; Morbidity - disease rate; Neurobiology; Participant; Pattern; Physiological; Plant Roots; Population; Post-Traumatic Stress Disorders; Predisposition; Prevalence; Prevention; Process; Psychopathology; Public Health; Recovery; Risk; Safety; Severities; Stimulus; Symptoms; Techniques; Testing; Time; Trauma; Veterans; Work; cognitive neuroscience; cohort; combat; combat veteran; curative treatments; effective therapy; innovation; insight; memory process; military veteran; mortality; movie; neural circuit; neurofeedback; new therapeutic target; novel; patient population; post-traumatic symptoms; prevent; psychopharmacologic; relating to nervous system; resilience; response; therapy development; tool; trauma exposure

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.

项目摘要 创伤后应激障碍(PTSD)是一种以异常为特征的衰弱心理障碍 对威胁刺激的反应，是与重大发病率和死亡率相关的重大公共卫生问题， 尤其是在退伍军人群体中。治疗创伤后应激障碍的唯一有效疗法(即暴露疗法) 新的安全反应与有问题的威胁反应竞争并掩盖--但不会改变--。 此外，没有确凿证据支持精神药理学干预治疗创伤后应激障碍， 这进一步突显了对这种疾病的神经生物学知识的缺乏。例如，尽管 创伤暴露在普通人群和退伍军人中的流行率、特定易感性或 决定随后的精神病理的风险和弹性的变化是未知的。实验室模型 经常用于研究创伤后应激障碍的威胁记忆过程-然而，这些模型消除了 典型的在创伤后应激障碍中触发异常反应的生动的、多重的刺激。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。一种理解 创伤后应激障碍患者对自然威胁刺激异常反应的精确神经生物学损伤 将支持超越掩盖症状、针对根本问题并为治愈铺平道路的疗法 干预措施。本提案旨在定义与创伤后应激障碍相关的失调神经回路 在伊拉克或阿富汗服役的美国退伍军人的症状严重程度。我们将新利用 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)，以确定自然威胁暴露期间大脑活动的动态模式。通过监控 神经表征的动态化、自然化的刺激，我们将判断大脑是否存在差异性 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，因为威胁刺激的异常神经表征必然会导致紊乱 对这些失调表征的生理反应。由于创伤后应激障碍中的异常威胁反应 既由外部环境中的威胁性线索触发，也由内部重新体验过去的负面情绪触发 关于记忆，本提案将对两种情况进行评估和量化。它将评估神经处理 通过量化一部战斗电影引发的神经表征的稳定性，来分析厌恶的、自然主义的刺激。 该提案还将通过量化稳定性来评估个人创伤记忆的神经处理 在自传体记忆的重复重新激活过程中的神经表征。这个项目将 加深我们对威胁刺激是否以及如何在创伤后应激障碍和创伤后应激障碍中的不同表现的理解 促进制定超越掩盖创伤后应激障碍症状的治疗方案，并针对 潜在的认知障碍。