Neural mechanisms involved in contextual processing in PTSD

参与 PTSD 情境处理的神经机制

• 批准号: 10378188
• 负责人: Elizabeth Duval
• 金额: $ 5.09万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-24 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378188
• 关键词: Anxiety Disorders; Behavioral; Brain; Chronic; Clinical; Cognitive deficits; Control Groups; Cues; Data; Development; Fright; Future; Goals; Hippocampus (Brain); Impairment; Learning; MRI Scans; Magnetic Resonance Imaging; Maintenance; Memory; Mentored Patient-Oriented Research Career Development Award; Methods; National Institute of Mental Health; Neurocognitive; Outcome; Participant; Patients; Pattern; Performance; Post-Traumatic Stress Disorders; Prefrontal Cortex; Retrieval; Role; Stimulus; Time; Training; base; cognitive training; improved; memory encoding; memory retrieval; military service; neural circuit; neuroimaging; neuromechanism; service member; stem; translational neuroscience; trauma exposure; traumatic event

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.

总结/摘要 创伤后应激障碍（PTSD）是一种严重的、使人衰弱的病症，其特征是恐惧的变化 表达和调节。PTSD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”上下文来消除潜在威胁线索的歧义。一些 认知缺陷可能是PTSD中受损的上下文处理的基础，包括编码缺陷和 检索上下文信息。模式分离（区分相似但不同的 刺激）和模式完成（基于部分信息识别先前编码的刺激的能力） 被认为分别是记忆编码和提取的基础。该项目的目标是 系统地探索记忆功能，如PTSD患者的模式分离和模式完成，创伤 暴露对照（TC）和健康对照（HC），使用神经认知任务和恐惧学习任务。我们将 研究背景记忆和模式分离/完成在恐惧调制中的作用 表情我们的目的是检查1）模式分离和模式完成能力的创伤后应激障碍和 潜在的神经回路，以及2）模式分离和模式完成之间的关系 PTSD患者在恐惧学习过程中的能力和背景处理缺陷。参与者将完成一个恐惧 学习任务，以评估上下文处理和恐惧调制。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 和前额叶皮层激活模式大脑激活和行为表现将进行比较 在所有任务中PTSD，TC和HC组之间进行比较，以更好地了解这些海马神经元的贡献。 恐惧学习和反应能力的改变。为了顺利完成拟议项目， 培训目标包括1）先进的MRI处理和分析，2）海马机制， 学习和记忆，3）PTSD的神经认知评估，以及4）临床转化 神经科学NIMH K23项目将为R级应用提供丰富的试验数据， 保护候选人获得神经成像方法高级培训的时间，同时扩大她的 焦虑症表现背后的神经认知机制的专业知识。该项目的成果 有很强的潜力，以提高我们的理解机制参与创伤后应激障碍的发展， 最终改善现有的治疗方法。

项目成果

Altered resting-state functional connectivity in adolescents is associated with PTSD symptoms and trauma exposure

• DOI: 10.1016/j.nicl.2020.102215
• 发表时间: 2020-02
• 期刊: NeuroImage : Clinical
• 作者: Jony Sheynin;Jony Sheynin;E. Duval;Yana Lokshina;Yana Lokshina;J. C. Scott;Mike Angstadt;Daniel A Kessler;Li Zhang;Li Zhang;R. E. Gur;R. Gur;Israel Liberzon;Israel Liberzon