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.

摘要/摘要 创伤后应激障碍（PTSD）是一种严重且令人衰弱的疾病，其特征是恐惧的变化 表达和调制。恐惧调节在PTSD患者中的定义可能至少部分源于 难以使用“安全”和“危险”环境来消除潜在威胁线索的歧义。许多 认知缺陷可能是PTSD中上下文处理受损的基础，包括编码和 检索上下文信息。模式分离（能够区分相似但不同的能力 刺激）和模式完成（能够根据部分信息识别先前编码的刺激） 据信分别是编码和检索的基础。这个项目的目标是 系统上探测记忆功能，例如PTSD患者的模式分离和模式完成，创伤 使用神经认知任务和恐惧学习任务，裸露的控制（TC）和健康控制（HC）。我们将 调查记忆在恐惧调制中的上下文和模式分离/完成的作用 表达。我们的目的是检查1）PTSD和PTSD的模式分离和模式完成能力 潜在的神经回路，以及2）模式分离与模式完成之间的关系 PTSD中恐惧学习期间的能力和上下文处理定义。参与者将完成恐惧 学习任务以评估上下文处理和恐惧调制。上下文信息的记忆，模式 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。将比较大脑激活和行为表现 在所有任务中的PTSD，TC和HC组之间，以更好地了解这些海马的贡献 PTSD中恐惧学习和反应性改变的缺陷。为了成功完成拟议的项目， 培训对象包括1）高级MRI处理和分析，2）海马机制 学习与记忆，3）PTSD的神经认知评估，4）临床翻译 神经科学。拟议的NIMH K23奖将为R级申请提供丰富的试点数据， 保护候选人获得神经影像学方法的高级培训的时间，同时扩大了她 焦虑症表现的神经认知机制方面的专业知识。这个项目的结果 具有强大的潜力，可以增强我们对PTSD开发涉及机制的理解和 维护，最终改善现有治疗方法。

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