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

用于中风后疲劳康复的神经调节：一项 rTMS 试点研究

• 批准号: 10535516
• 负责人: John Harvey Kindred
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-01 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10535516
• 关键词: Acceleration; Affect; American Heart Association; Anxiety; Appointment; Attention; Award; Behavior; Bilateral; Bioenergetics; Biological Markers; Caregivers; Central Nervous System; Characteristics; Chronic Fatigue Syndrome; Cladribine; Clinical; Clinical assessments; Cognition Disorders; Coin; Colorado; Communities; Contract Services; Data; Development; Diagnostic; Dimensions; Doctor of Philosophy; Effectiveness; Environment; Evidence based treatment; FDA approved; Fatigue; Foundations; Frequencies; Functional disorder; Glutamates; Goals; Human; Individual; Intervention; K-Series Research Career Programs; Knowledge; Laboratories; Learning; Left; Lesion; Location; Long COVID; Lower Extremity; Magnetic Resonance Spectroscopy; Manuscripts; Measures; Medical; Medical center; Mental Depression; Mental disorders; Mentorship; Methods; Motor; Motor Cortex; Multiple Sclerosis; Nature; Nervous System; Nervous System Physiology; Neurocognitive; Neurologic; Peer Review; Performance; Persons; Physical Function; Physical activity; Physiologic pulse; Pilot Projects; Play; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Postdoctoral Fellow; Prefrontal Cortex; Prevalence; Psyche structure; Publications; Publishing; Quality of life; Recording of previous events; Rehabilitation therapy; Research; Research Personnel; Role; Scientist; Services; Severities; Signal Transduction; South Carolina; Stroke; Structure; System; Testing; Therapeutic; Training; Transcranial magnetic stimulation; Traumatic Brain Injury; United States; Universities; Update; Upper Extremity; Veterans; Veterans Health Administration; Work; active duty; career; career development; chronic stroke; cognitive function; college; cost; disability; effective intervention; effective therapy; efficacy testing; evidence base; experience; expiration; frontal lobe; improved; insight; marine; member; military veteran; multidisciplinary; negative affect; nervous system disorder; neural circuit; neuroimaging; neurophysiology; neuropsychiatry; neuroregulation; noninvasive brain stimulation; novel; novel therapeutic intervention; pharmacologic; post stroke; programs; psychologic; rehabilitation research; repetitive transcranial magnetic stimulation; research and development; response; skills; social; statistics; stroke rehabilitation; therapy design; tool

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.

该拟议职业发展奖（CDA-2）的长期目标是加速我的培训和 发展，以便我能够建立一条独立的研究路线，揭示因果关系 疲劳并开发有效的循证疗法来治疗患有神经系统疾病的退伍军人的疲劳。 在上大学之前，我在美国海军陆战队服役了九年，并获得了 我在服务合同到​​期后光荣退役。 2017 年在科罗拉多州立大学获得生物能学学位。毕业后，我开始在该大学担任博士后职位 南卡罗来纳医科大学与 Mark G. Bowden 博士（PT、Ph.D）合作 博士职位后，我在 Ralph H. Johnson VA 医疗中心获得了 WOC 任命，并获得了 VA 康复研究与发展职业发展奖 – 1 于 2019 年 10 月开始。 在我的研究之旅开始时，我已经发表了 22 篇同行评审的手稿，其中 12 篇作为第一作者。 最近的出版物集中在测量神经系统的神经生理状态和 这些最新的手稿基于在中风后残疾中收集的数据。 在我到达之前，我在 Ralph H. Johnson 的实验室工作过，合著者包括该组织的几位成员。 完成 CDA-1（结束日期：2021 年 9 月 30 日）后，我集中了注意力。 该 CDA-2 提案将为我提供有关中风后疲劳的神经生理学生物标志物的信息。 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 应用神经调节治疗将为我提供建立独立 VA 的基础。 支持的研究计划，重点是通过一系列神经系统来减少退伍军人疲劳的影响 组建的导师团队由中风后康复专家组成， 高达 92% 的中风后患者会感到疲劳。 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。 存在于退伍军人社区内的许多其他神经群体中，例如创伤性脑损伤， 多发性硬化症，以及新发明的长新冠病毒的知识和进展。 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 第一个目标是测试成熟的重复神经调节疗法的效果。 经颅磁刺激（rTMS）旨在减轻中风后疲劳的严重程度。 基于从其他神经精神/认知障碍和治疗研究中获得的理论原理 尝试减少其他神经系统疾病引起的疲劳，参与的退伍军人将接受高频治疗。 rTMS 作用于额叶，左前额叶背外侧皮质或双侧运动皮质。 我希望证明 rTMS 可用于治疗其他神经系统疾病中的疲劳。 减轻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取决于。 研究的第二个目标是基于技能和知识。 在 CDA-1 中开发后，我计划在这个项目中识别额外的疲劳神经生理学生物标志物。 我将评估退伍军人上肢和下肢感觉运动网络的谷氨酸活性/信号传导 有或没有中风后疲劳，我希望表明疲劳组会表现出谷氨酸功能障碍， 通过皮质内促进和对配对联想的促进反应的更大不对称性来衡量 与非疲劳组相比，谷氨酸和相关代谢物的鉴定。 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 用于中风后疲劳和其他神经系统疾病引起的疲劳。