Neural mechanisms involved in contextual processing in PTSD

摘要/摘要 创伤后应激障碍(PTSD)是一种严重的、令人衰弱的疾病，其特征是恐惧的变化 表达和调制。创伤后应激障碍患者的恐惧调节缺陷可能至少部分源于 难以使用“安全”和“危险”语境来消除潜在威胁线索的歧义。一批 认知缺陷可能是创伤后应激障碍的背景处理受损的基础，包括编码和 检索上下文信息。模式分离(区分相似但不同的能力 刺激)和模式完成(根据部分信息识别先前编码的刺激的能力) 据信分别是记忆编码和提取的基础。这个项目的目标是 系统探讨创伤后应激障碍患者的记忆功能，如模式分离和模式完成 暴露对照组(TC)和健康对照组(HC)，使用神经认知任务和恐惧学习任务。我们会 考察情境记忆和模式分离/完成在恐惧调制中的作用 表情。我们的目标是考察1)创伤后应激障碍患者的模式分离和模式补全能力 潜在神经回路，以及2)模式分离和模式完成之间的关系 创伤后应激障碍患者恐惧学习过程中的能力和情境加工缺陷。参与者将完成一种恐惧 评估情境加工和恐惧调制的学习任务。对上下文信息、模式的记忆 在MRI扫描期间，将检查分离和模式完成，以识别相关的海马区 以及前额叶皮质的激活模式。大脑的激活和行为表现将被比较 在所有任务中在PTSD、TC和HC组之间进行比较，以更好地了解这些海马区的贡献 创伤后应激障碍中恐惧学习和反应能力改变的缺陷。为了顺利完成拟议的项目， 培训目标包括1)先进的MRI处理和分析，2)海马区机制 学习和记忆，3)创伤后应激障碍的神经认知评估，4)临床翻译 神经科学。这项拟议的NIMH K23奖项将为R级应用程序提供丰富的试点数据，并 保护候选人获得神经成像方法高级培训的时间，同时拓宽她的视野 焦虑症陈述背后的神经认知机制方面的专业知识。这个项目的结果是 有很强的潜力加强我们对创伤后应激障碍发生和发展的机制的了解 维护，以最终改善现有的治疗方法。

Summary/Abstract Posttraumatic stress disorder (PTSD) is a serious and debilitating condition, characterized by changes in fear expression and modulation. The fear modulation deficits in PTSD patients likely stem, at least in part, from difficulties using “safe” and “danger” contexts to disambiguate potentially threatening cues. A number of cognitive deficits may underlie impaired contextual processing in PTSD, including deficits in encoding and retrieval of contextual information. Pattern separation (ability to distinguish between similar but different stimuli) and pattern completion (ability to identify a previously encoded stimulus based on partial information) are believed to underlie memory encoding and retrieval, respectively. The goal of this project is to systematically probe memory function, like pattern separation and pattern completion in PTSD patients, trauma exposed controls (TC), and healthy controls (HC) using neurocognitive tasks and a fear learning task. We will investigate the roles of memory for context and pattern separation/completion in the modulation of fear expression. We aim to examine 1) Pattern Separation and Pattern Completion abilities in PTSD and the underlying neural circuits, and 2) Relationships between Pattern Separation and Pattern Completion abilities and context processing deficits during fear learning in PTSD. Participants will complete a fear learning task to assess contextual processing and fear modulation. Memory for contextual information, pattern separation, and pattern completion will be examined during MRI scanning to identify associated hippocampal and prefrontal cortex activation patterns. Brain activation and behavioral performance will be compared between PTSD, TC, and HC groups across all tasks to better understand contributions of these hippocampal deficits to altered fear learning and reactivity in PTSD. In order to successfully complete the proposed project, training objectives include 1) advanced MRI processing and analysis, 2) hippocampal mechanisms of learning and memory, 3) neurocognitive assessment of PTSD, and 4) clinical translational neuroscience. This proposed NIMH K23 award will provide rich pilot data for an R-level application and protected time for the candidate to obtain advanced training in neuroimaging methods, while broadening her expertise in neurocognitive mechanisms underlying anxiety disorder presentations. The outcome of this project has strong potential to enhance our understanding of mechanisms involved in PTSD development and maintenance, to eventually improve existing treatments.