Neuromodulation for Rehabilitation of Post-Stroke Fatigue: An rTMS Pilot Study

这个拟议的职业发展奖(CDA-2)的长期目标是加快我的培训和 发展，这样我就可以建立一个独立的研究队伍，来揭开原因和后果 并开发有效的循证疗法来治疗有神经疾病的退伍军人的疲劳。 在我读大学之前，我在美国海军陆战队服役九年，获得了 在我的服务合同期满时光荣地解聘。我完成了我的人类学博士学位 2017年，科罗拉多州立大学的生物能量学。毕业后，我开始在哈佛大学从事博士后工作 南卡罗来纳医科大学与马克·G·鲍登博士合作。在开始我的职位后不久- 博士职位，我获得了拉尔夫·H·约翰逊退伍军人医疗中心的WOC职位，并获得了 退伍军人康复研究与发展职业发展奖-1，始于2019年10月。自.以来 在我的研究之旅的开始，我发表了22篇同行评议的手稿，其中12篇是第一作者。我的 最近的大多数出版物都集中在测量神经系统的神经生理状态和 将这种状态与中风后的残疾联系起来。这些最新的手稿是基于在 在我到达之前，拉尔夫·H·约翰逊的实验室和合著者包括这个团队的几名成员 提案的指导团队。在完成我的CDA-1(截止日期2021年9月30日)后，我将注意力集中在 卒中后疲劳的神经生理学生物标志物。这份CDA-2提案将为我提供 有机会学习新的神经生理学评估方法，并提高我的知识和能力 应用神经调节性治疗。这些技能将为我建立独立的退伍军人管理局奠定基础- 支持的研究计划侧重于通过一系列神经学研究减少退伍军人疲劳的影响 条件。组建的导师团队由中风后康复专家组成， 神经调节、神经成像和临床评估。高达92%的人在中风后会感到疲劳。 疲劳会对身体和精神表现产生负面影响，导致生活质量下降。疲劳也是 存在于退伍军人社区内的许多其他神经科人群中，例如创伤性脑损伤， 多发性硬化症，以及新创造的长冠状病毒现象。知识和技术方面的进展 对中风后疲劳的了解可能会导致退伍军人中其他临床人群的进步 社区。第一个目标是测试一种公认的神经调节疗法的效果，这种疗法是重复的 经颅磁刺激(RTMS)，对减轻中风后疲劳的严重程度。这一目标是有前提的。 论其他神经精神病学/认知障碍研究的理论原理及治疗 试图减少其他神经系统疾病的疲劳感。参赛退伍军人将获得高频 RTMS至额叶，左侧前额叶背外侧皮质或双侧运动皮质。这些 在其他神经疾病中，位置也与疲劳有关。我希望展示rtms可以用来 降低中风后疲劳的严重程度。然而，治疗的有效性和部位可能部分是 取决于个体特征。研究的第二个目的是基于技能和知识 在CDA-1中开发的，我计划识别其他疲劳的神经生理学生物标记物。在这个项目中， 我将评估退伍军人上肢和下肢感觉运动网络的谷氨酸能活动/信号 有或没有中风后疲劳。我希望证明疲劳组会表现出谷氨酸能功能障碍， 通过皮质内易化的更大不对称性和对配对联想的易化反应来衡量 刺激，与非疲劳组相比。谷氨酸及其相关代谢物的鉴定 卒中后疲劳的病理生理因素可能有助于开发新的治疗方法 用于中风后疲劳和其他神经疾病的疲劳。

The long-term goal of this proposed career development award (CDA-2) is to accelerate my training and development so that I can establish an independent line of research unraveling the causes and consequences of fatigue and to develop effective evidence-based therapies for fatigue in Veterans with neurological conditions. Before my collegiate studies, I served nine years on active duty in the United States Marine Corps and received an Honorable Discharge upon the expiration of my service contract. I completed my Ph.D. in Human Bioenergetics at Colorado State University in 2017. Upon graduation, I began a post-doctoral position at the Medical University of South Carolina working with Dr. Mark G. Bowden, PT, Ph.D. Shortly after starting my post- doc position, I acquired a WOC appointment at the Ralph H. Johnson VA Medical Center and was awarded a VA Rehabilitation Research and Development Career Development Award – 1 that began in Oct 2019. Since the beginning of my research journey, I have published 22 peer-reviewed manuscripts, 12 as the first author. My most recent publications have centered on measuring the neurophysiological state of the nervous system and relating that state to post-stroke disability. These most recent manuscripts are based on data collected at the laboratories at Ralph H. Johnson before my arrival and the co-authors include several of the members of this proposal’s mentorship team. Upon completing my CDA-1 (end date Sep 30, 2021), I have focused my attention on the neurophysiological biomarkers of post-stroke fatigue. This CDA-2 proposal will provide me with the opportunity to learn new neurophysiological assessment methods and advance my knowledge and ability to apply neuromodulatory treatments. These skills will provide me the foundation to build an independent VA- backed research program focusing on reducing the impact of fatigue in Veterans with an array of neurological conditions. The assembled mentorship team is composed of experts in post-stroke rehabilitation, neuromodulation, neuroimaging, and clinical assessment. Up to 92% of people post-stroke experience fatigue. Fatigue negatively affects physical and mental performance leading to a lower quality of life. Fatigue is also present in many other neurological populations within the Veteran community, such as traumatic brain injury, multiple sclerosis, and the newly coined phenomenon of Long-COVID. Advances in the knowledge and understanding of post-stroke fatigue are likely to lead to advances in other clinical populations within the Veteran community. The first aim is to test the effects of a well-established neuromodulatory therapy, repetitive transcranial magnetic stimulation (rTMS), on reducing the severity of post-stroke fatigue. This aim is predicated on theoretical principles obtained from the study of other neuro-psychiatric/-cognitive disorders and therapeutic attempts to reduce fatigue in other neurological illnesses. Participating Veterans will receive high-frequency rTMS to the frontal lobe, either the left prefrontal dorsolateral cortex or bilaterally to the motor cortices. These locations have been implicated in fatigue in other neurological conditions. I expect to show rTMS can be used to reduce post-stroke fatigue severity. However, the effectiveness and location of treatment may partially be dependent on individual characteristics. The second aim of the study is based on the skills and knowledge developed in the CDA-1, I plan on identifying additional neurophysiological biomarkers of fatigue. In this project, I will assess glutamatergic activity/signaling of the upper and lower extremity sensorimotor network of Veterans with and without post-stroke fatigue. I expect to show that the fatigued group will show glutamatergic dysfunction, measured by greater asymmetries in intracortical facilitation and the facilitatory response to paired associative stimulation, compared to the non-fatigued group. Identification of glutamate and related metabolites as a pathophysiological contributor to post-stroke fatigue may help in the development of new therapeutic approaches for post-stroke fatigue and fatigue in other neurological conditions.