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

项目摘要/摘要 这项导师研究科学家发展奖(K01)申请是一项全面的培训计划，以 为应聘者提供建立独立的岗位培训计划所需的其他高级技能 使用神经成像方法研究创伤应激障碍(PTSD)。应聘者之前在 神经成像使她磨练了许多实现这一目标所必需的技能。然而，她要求 以下领域的其他培训和经验：(1)创伤后应激障碍的教学和研究培训；(2) 高场(7T)磁共振波谱(MRS)，特别是功能磁共振波谱(FMRS)的先进技术；(3) 神经成像分析的编程技能；以及(4)写作和职业发展。建议数 这项研究将调查创伤后应激障碍患者认知缺陷的神经代谢和功能相关性。具有以下特征的人 除了核心症状外，创伤后应激障碍通常还会报告注意力、注意力和记忆力方面的困难 侵扰性思维、回避和过度唤醒。这些认知症状尤其令人苦恼。 并导致社会和职业功能不佳，生活质量不佳。神经心理测试表明 工作记忆(WM)是创伤后应激障碍的一种认知过程，但WM功能障碍的神经基础 还没有被很好地理解。了解这些缺陷的性质很重要，不仅因为WM是至关重要的 不仅是因为西医促进了常见的治疗策略，如认知 行为疗法。越来越多的证据表明，创伤后应激障碍患者的关键脑区存在谷氨酸能功能障碍。 这些异常可能是功能成像观察到的不同激活模式的基础 患有创伤后应激障碍的人执行WM任务；然而，这还没有得到直接测试。磁共振 光谱学(MRS)在缩小这一差距方面与最近的创伤后应激障碍的活体研究显示出了巨大的希望 显示出谷氨酸水平的紊乱。然而，这些研究中没有一项在活体内与这些相关。 神经激活的新陈代谢测量。功能性MRS(FMRS)可以通过以下方式潜在地解决这个问题 测量神经活动对刺激的反应所引起的神经代谢变化。与传统的MRS不同， 其在休眠状态期间获取数据，FMRS在参与者从事执行时获取数据 一项任务，从而提供了神经代谢物的动态而不是静态的概况。在此应用程序中，我们 建议在7T开发FMRS技术，以探索导致WM缺陷的神经机制 创伤后应激障碍。这项研究将结合传统(静态)磁共振成像、功能磁共振成像(FMRI)和先进的动态磁共振成像 探讨西医过程中神经激活与基础神经化学的关系 创伤后应激障碍。由于FMR和fMRI探测神经元放电和突触活动的不同方面，因此组合 这些技术的方法可以更好地描述创伤后应激障碍WM缺陷的神经生物学特征。如果 如果成功，这些方法可能会被用来测试当前治疗的效果并确定 潜在的目标是开发新的药物来改善创伤后应激障碍患者的预后。

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.