Neurobiological Mechanisms of Fatigue in Health and after COVID-19

健康人和 COVID-19 后疲劳的神经生物学机制

• 批准号: 10722396
• 负责人: Agostina Casamento Moran
• 金额: $ 9.91万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722396
• 关键词: Acute; Affect; Affective; Age; Behavioral; Biofeedback; Biomedical Engineering; Brain; COVID-19; Chronic Disease; Clinical; Computing Methodologies; Data; Decision Making; Development Plans; Dimensions; Economic Burden; Epidemiology; Exhibits; Faculty; Fatigue; Feeling; Foundations; Future; Goals; Health; Healthcare Systems; Individual; Intervention; Isometric Exercise; Laboratories; Learning; Magnetic Resonance Imaging; Measures; Mentors; Methods; Muscle; Nature; Neurologic; Participant; Patient Self-Report; Phase; Physiology; Positioning Attribute; Post-Acute Sequelae of SARS-CoV-2 Infection; Psychophysiology; Race; Research; Research Personnel; SARS-CoV-2 infection; Secure; Symptoms; Syndrome; Techniques; Training; United States; United States National Institutes of Health; career; career development; common symptom; computational neuroscience; disabling symptom; experimental study; motor control; neural correlate; neurobiological mechanism; neuroeconomics; neuroimaging; neuromuscular; novel; prevent; response; sex; skill acquisition; skills; translational neuroscience; willingness

PROJECT SUMMARY Fatigue is one of the most common and debilitating symptoms in neurological, psychiatric, and other chronic illnesses; however, it remains poorly understood and undertreated. Post-acute sequelae of SARS-CoV-2 infection (PASC) is a novel syndrome characterized by a range of symptoms present four or more weeks after the acute phase of COVID-19. Among these symptoms, severe fatigue is the most common and debilitating. Critical hurdles to understanding and treating fatigue include its multidimensional nature and the lack of quantitative methods to characterize it. In this MOSAIC K99/R00 application, I propose to use a novel `fatigue paradigm' that leverages neuromuscular, neuroeconomic, and computational methods to objectively investigate the neurobiological mechanisms of three features of fatigue in healthy individuals and individuals with PASC: feeling of weariness (how weary one feels), sense of effort (how one perceives a previously exerted force), and willingness to exert effort (an individual's decision to engage in effortful actions). My central hypothesis is that fatigue is comprised of at least three separable features, which represent distinct psychophysiological aspects, have unique neural correlates, and are differentially affected by PASC. The experiments proposed for the K99 Phase, which will be executed in Dr. Vikram Chib's Neuroeconomic Laboratory in the Kennedy Krieger Institute and Department of Biomedical Engineering at Johns Hopkins, will identify the brain network(s) encoding the features of fatigue in healthy individuals (Aim 1) and investigate how fatigue manifests in individuals with PASC (Aim 2). Through these projects, and the guidance of my mentoring team (Drs. Vikram Chib, Karen Quigley, Laura Malone, and Martin Lindquist), I will acquire complementary expertise in neuroimaging, psychophysiology, and computational and translational neuroscience. In the R00 Phase, I propose to merge my expertise in neuromuscular physiology and motor control with my newly acquired skills to identify the brain network(s) encoding fatigue in PASC (Aim 3). This Phase will be executed in my own laboratory upon securing an independent faculty position. The current epidemiological significance of fatigue and PASC makes this proposal especially timely and important, as it will significantly advance our understanding of fatigue and contribute to the NIH's RECOVER initiative. Further, the proposed research and training plans will allow me to accomplish my long-term career goal of becoming an independent investigator who will distinguish the neurobiological mechanisms of fatigue in different illnesses and develop targeted clinical interventions.

项目摘要 疲劳是神经，精神病和其他慢性的最常见和令人衰弱的症状之一 疾病；但是，它的理解和治疗程度不足。 SARS-COV-2的急性后遗症 感染（PASC）是一种新型综合征，其特征是一系列症状，出现了四个或更长时间后 COVID-19的急性相。在这些症状中，严重的疲劳是最常见和令人衰弱的。 理解和治疗疲劳的关键障碍包括其多维性质和缺乏 定量方法以表征它。在此Mosaic K99/R00应用中，我建议使用新颖的疲劳 利用神经肌肉，神经经济学和计算方法的范式' 健康个体和患有PASC的个体疲劳特征的三种特征的神经生物学机制： 疲倦的感觉（一个人的疲倦），努力感（人们如何看待先前施加的力量）和 愿意付出努力（个人做出努力行动的决定）。我的中心假设是 疲劳由至少三个可分离特征组成，这些特征代表了不同的心理生理方面， 具有独特的神经相关性，并受PASC差异影响。 为K99阶段提出的实验，该实验将在Vikram Chib博士的神经经济学中执行 肯尼迪·克里格研究所（Kennedy Krieger Institute）和约翰·霍普金斯（John Hopkins）生物医学工程系的实验室，威尔 确定在健康个体中编码疲劳特征的大脑网络（AIM 1），并研究如何 疲劳在患有PASC的个体中表现出来（AIM 2）。通过这些项目以及我的指导的指导 团队（Vikram Chib博士，Karen Quigley，Laura Malone和Martin Lindquist），我将获得补充 神经影像学，心理生理学以及计算和转化神经科学方面的专业知识。在R00中 阶段，我建议将我在神经肌肉生理学和运动控制方面的专业知识与我的新近获得 识别编码PASC疲劳的大脑网络的技能（AIM 3）。这个阶段将自己执行 确保独立教师职位的实验室。 疲劳和PASC的当前流行病学意义使该提议特别及时， 重要的是，因为这将大大提高我们对疲劳的理解，并为NIH的恢复做出贡献 倡议。此外，拟议的研究和培训计划将使我能够实现我的长期职业目标 成为一名独立研究者，他将区分疲劳的神经生物学机制 不同的疾病并发展有针对性的临床干预措施。