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: 9762985
• 负责人: Meredith A Reid
• 金额: $ 16.04万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762985
• 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; 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.

项目总结/摘要 这个指导研究科学家发展奖（K 01）应用程序是一个全面的培训计划， 为候选人提供建立独立的职位计划所需的额外和先进的技能， 创伤性应激障碍（PTSD）研究使用神经影像学方法。候选人之前接受的培训 神经影像学使她磨练了许多实现这一目标所需的技能。然而，她要求 在以下领域的额外培训和经验：（1）创伤后应激障碍的教学和研究培训;（2） 高场（7 T）磁共振波谱（MRS）的先进技术，特别是功能性MRS（fMRS）;（3） 神经影像学分析的编程技能;（4）写作和专业发展。拟议 这项研究将调查创伤后应激障碍中认知缺陷的神经代谢和功能相关性。人 PTSD除了核心症状外，通常还报告注意力集中，注意力和记忆力困难 侵入性思维回避和过度兴奋这些认知症状可能特别令人痛苦 并导致社会和职业功能低下以及生活质量低下。神经心理测试表明 工作记忆（WM）是PTSD患者的认知过程之一，但WM功能障碍的神经基础 并没有得到很好的理解。理解这些缺陷的性质是重要的，不仅因为WM是至关重要的 日常功能，但也因为WM促进常见的治疗策略，如认知 行为疗法越来越多的证据表明，PTSD患者的关键脑区存在神经元功能障碍。 这些异常可能是功能成像观察到的差异激活模式的基础， 患有PTSD的人执行WM任务;然而，这还没有被直接测试。磁共振 磁共振波谱（MRS）已被证明是巨大的承诺，在填补这一差距，最近在体内研究创伤后应激障碍 显示谷氨酸水平受到破坏。然而，这些研究中没有一个在体内将这些相关联 代谢测量与神经激活。功能性MRS（fMRS）可以通过以下方式解决这个问题： 测量由神经活动响应刺激而引起的神经代谢变化。与传统MRS不同， 在休息状态下采集数据，fMRS在参与者参与表演时采集数据， 一项任务，从而提供了一个动态的，而不是静态的神经代谢物的档案。在本申请中，我们 建议开发7 T的fMRS技术，以探索导致WM缺陷的神经机制， 创伤后应激障碍本研究将结合联合收割机传统的（静态）磁共振波谱，功能磁共振成像（fMRI），和先进的动态fMRS 研究WM过程中神经激活与脑内神经化学的关系， 创伤后应激障碍由于fMRS和fMRI探测神经元放电和突触活动的不同方面， 这些技术的方法可以更好地表征PTSD中WM缺陷的神经生物学基础。如果 成功的，这些方法可能被用来测试目前的治疗效果，并确定 开发新药物以改善PTSD患者的结局的潜在目标。