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

这个职业发展奖（CDA-2）的长期目标是加速我的培训， 这样我就可以建立一个独立的研究路线， 疲劳和开发有效的循证治疗疲劳的退伍军人与神经系统疾病。 在我上大学之前，我在美国海军陆战队服役了九年， 在我的服务合同到期后光荣退役。我完成了博士学位人 2017年在科罗拉多州立大学的生物能量学。毕业后，我开始了博士后的工作， 南卡罗来纳州医科大学的马克·G。Bowden，PT，Ph.D.在我开始写这篇文章后不久- 博士的位置，我获得了一个在拉尔夫H。约翰逊退伍军人医疗中心，并被授予 VA康复研究与发展职业发展奖- 1于2019年10月开始。以来 在我的研究之旅开始时，我已经发表了22篇同行评议的手稿，其中12篇是第一作者。我 最近的出版物集中于测量神经系统的神经生理状态 将这种状态与中风后残疾联系起来。这些最新的手稿是基于收集的数据， Ralph H的实验室约翰逊在我到来之前和合著者包括几个成员， 提案的指导团队。在完成CDA-1（结束日期2021年9月30日）后，我将注意力集中在 中风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， 应用神经调节治疗。这些技能将为我提供建立一个独立的VA的基础- 支持的研究计划，重点是减少疲劳的影响，在退伍军人与一系列的神经系统疾病 条件这支由中风后康复专家组成的辅导团队， 神经调节、神经成像和临床评估。高达92%的中风后患者会感到疲劳。 疲劳对身体和精神表现产生负面影响，导致生活质量降低。疲劳也是 存在于退伍军人社区内的许多其他神经系统人群中，例如创伤性脑损伤， 多发性硬化症和新发明的新冠肺炎。知识的进步和 对中风后疲劳的理解可能会导致退伍军人中其他临床人群的进步 社区第一个目的是测试一种成熟的神经调节疗法的效果， 经颅磁刺激（rTMS），减少中风后疲劳的严重程度。这一目标的前提是 从其他神经精神/认知障碍和治疗的研究中获得的理论原则 试图减少其他神经系统疾病的疲劳。参与的退伍军人将获得高频率 rTMS到额叶，左前额叶背外侧皮质或双侧运动皮质。这些 在其他神经系统疾病中，这些位置与疲劳有关。我希望展示rTMS可以用来 减少中风后疲劳的严重程度。然而，治疗的有效性和位置可能部分取决于 取决于个人的特点。本研究的第二个目的是基于技能和知识 在CDA-1中开发的，我计划识别额外的疲劳神经生理学生物标志物。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神经元活动/信号传导 有无中风后疲劳我想展示的是疲劳组会表现出脑功能障碍， 通过皮质内易化和对配对联想的易化反应的更大不对称性来测量 与非疲劳组相比，谷氨酸及其相关代谢产物作为一种 中风后疲劳的病理生理学因素可能有助于开发新的治疗方法 中风后疲劳和其他神经系统疾病的疲劳。

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.