7T functional MRS of metabolite variations during working memory in subjects with post-traumatic stress disorder

创伤后应激障碍受试者工作记忆期间代谢物变化的 7T 功能 MRS

• 批准号: 10215508
• 负责人: Meredith A Reid
• 金额: $ 14.09万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215508
• 关键词: Address; Affect; Animal Model; Area; Attention; Back; Behavior; Brain; Brain region; Cessation of life; Chronic; Chronic stress; Cognitive Therapy; Cognitive deficits; Complex; Data; Data Analytics; Development; Disease; Distress; Exhibits; Fire - disasters; Fright; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Glutamates; Goals; Human; Impaired cognition; Individual; Lead; Link; Magnetic Resonance Spectroscopy; Measurement; Measures; Memory; Memory impairment; Mental disorders; Mentored Research Scientist Development Award; Metabolic; Metabolism; Methods; Modeling; National Institute of Mental Health; Natural Disasters; Nature; Neurobehavioral Manifestations; Neurobiology; Neurons; Neuropsychological Tests; Neurotransmitters; Occupational; Outcome; Participant; Pattern; Pharmaceutical Preparations; Physiological; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevalence; Quality of life; Reporting; Research; Research Proposals; Research Training; Rest; Sampling; Short-Term Memory; Stimulus; Symptoms; Synapses; System; Techniques; Testing; Thinking; Time; Training; Variant; Violence; Writing; cognitive process; common treatment; executive function; experience; imaging modality; improved outcome; in vivo; innovation; loved ones; memory process; neural circuit; neurochemistry; neuroimaging; neuroimaging marker; neuromechanism; novel; physical assault; programs; relating to nervous system; response; sexual assault; skills; social; traumatic event; treatment strategy; vehicular accident

PROJECT SUMMARY / ABSTRACT This Mentored Research Scientist Development Award (K01) application is a comprehensive training plan to provide the candidate with additional and advanced skills needed to establish an independent program of post- traumatic stress disorder (PTSD) research using neuroimaging methods. The candidate’s prior training in neuroimaging has allowed her to hone many skills necessary to achieve this goal. However, she requires additional training and experience in the following areas: (1) didactic and research training in PTSD; (2) advanced techniques in high-field (7T) MR spectroscopy (MRS), specifically functional MRS (fMRS); (3) programming skills for neuroimaging analyses; and (4) writing and professional development. The proposed study will investigate the neurometabolic and functional correlates of cognitive deficits in PTSD. People with PTSD commonly report difficulties with concentration, attention, and memory in addition to the core symptoms of intrusive thoughts, avoidance, and hyperarousal. These cognitive symptoms can be especially distressing and lead to poor social and occupational function and poor quality of life. Neuropsychological testing indicates that working memory (WM) is one cognitive process affected in PTSD, yet the neural basis of WM dysfunction is not well understood. Understanding the nature of these deficits is important not only because WM is crucial for everyday functioning but also because WM facilitates common treatment strategies, such as cognitive behavioral therapy. Converging evidence points to glutamatergic dysfunction in key brain regions in PTSD. These abnormalities could underlie the differential activation patterns observed with functional imaging when people with PTSD perform WM tasks; however, this has not been directly tested. Magnetic resonance spectroscopy (MRS) has demonstrated great promise in closing this gap with recent in vivo studies of PTSD showing disruptions of glutamate levels. However, none of these studies have correlated these in vivo metabolic measurements with neural activation. Functional MRS (fMRS) can potentially address this issue by measuring neurometabolic changes induced by neural activity in response to stimuli. Unlike traditional MRS, which acquires data during the resting state, fMRS acquires data while participants are engaged in performing a task, thereby providing a dynamic rather than static profile of neurometabolites. In this application, we propose to develop fMRS techniques at 7T to explore the neural mechanisms that contribute to WM deficits in PTSD. This research will combine traditional (static) MRS, functional MRI (fMRI), and advanced dynamic fMRS to investigate the relationship between neural activation during WM and the underlying neurochemistry in PTSD. Since fMRS and fMRI probe different aspects of neuronal firing and synaptic activity, the combined approach of these techniques could better characterize the neurobiology underlying WM deficits in PTSD. If successful, these methods could potentially be used to test the effects of current treatments and identify potential targets for the development of novel medications to improve outcomes for people with PTSD.

项目摘要 /摘要 这项指导的研究科学家发展奖（K01）应用程序是一项全面的培训计划 为候选人提供所需的其他技能，以建立独立的后计划 创伤应力障碍（PTSD）研究使用神经影像学方法。候选人先前的培训 神经影像使她能够获得实现这一目标所需的许多技能。但是，她需要 在以下领域的额外培训和经验：（1）PTSD中的教学和研究培训； （2） 高场（7T）MR光谱学（MRS）的晚期技术，特别是功能性MRS（FMRS）； （3） 神经影像分析的编程技能； （4）写作和专业发展。提议 研究将研究PTSD认知缺陷的神经代谢和功能相关性。有人 除核心符号之外 侵入性思想，回避和高度。这些认知症状可能特别令人痛苦 并导致社会和占用功能不佳以及生活质量差。神经心理学测试表明 该工作记忆（WM）是PTSD中影响的一个认知过程，但是WM功能障碍的神经基础 不太了解。理解这些缺陷的性质，不仅重要，因为WM至关重要 对于日常运作 行为疗法。融合证据指向PTSD关键大脑区域的谷氨酸能功能障碍。 这些异常可能是通过功能成像观察到的差分激活模式的基础 患有PTSD的人执行WM任务；但是，这尚未直接测试。磁共振 光谱法（MRS）在与最新的PTSD研究结束这一差距方面表现出了巨大的希望 显示谷氨酸水平的中断。但是，这些研究都没有将这些研究与体内相关 神经激活的代谢测量。功能性MRS（FMR）可以通过 测量神经代谢活性响应刺激引起的神经代谢变化。与传统太太不同， 在静止状态下获取数据，FMR在参与者进行执行时获取数据 一项任务，从而提供了神经代谢物的动态而不是静态轮廓。在此应用程序中，我们 在7T处开发FMRS技术的建议，以探索有助于WM定义的神经机制 PTSD。这项研究将结合传统（静态）MRS，功能性MRI（fMRI）和高级动态fMRS 研究WM期间神经激活与基础神经化学之间的关系 PTSD。由于fMR和fMRI探测神经元发射和突触活动的不同方面 这些技术的方法可以更好地表征WM在PTSD中定义的神经生物学。如果 成功，这些方法可能被可能用于测试当前治疗的影响并确定 开发新型药物以改善PTSD患者的预后的潜在靶标。