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.

该提议的职业发展奖（CDA-2）的长期目标是加速我的培训和 发展，以便我可以建立独立的研究线，以揭示原因和后果 疲劳并开发有效的具有神经系统疾病退伍军人的疲劳的有效循证疗法。 在我的大学学习之前，我在美国海军陆战队工作了9年，并接受了 我的服务合同到​​期后的光荣。我完成了博士学位在人类中 2017年在科罗拉多州立大学的生物能学。毕业后，我开始了博士后职位 南卡罗来纳州医科大学与马克·G·鲍登（Mark G. Bowden）博士合作开始我的职位后不久 DOC职位，我在Ralph H. Johnson VA医疗中心获得了WOC任命，并获得了 VA康复研发职业发展奖 - 1年10月1日。 在研究之旅的开始，我已经出版了22个同行评审的手稿，其中12本作为第一作者。我的 最新出版物的重点是衡量神经系统的神经生理状态和 将该状态与中风后残疾联系起来。这些最新的手稿基于在 拉尔夫·H·约翰逊（Ralph H. 提案的精明团队。完成我的CDA-1（2021年9月30日结束日期）后，我集中了我的注意力 在触摸后疲劳的神经生理生物标志物上。这个CDA-2提案将为我提供 学习新的神经生理评估方法并提高我的知识和能力的机会 应用神经调节治疗。这些技能将为我提供建立独立的VA-的基础 支持的研究计划的重点是减少疲劳对退伍军人的影响 状况。集会的Mentalship团队由中风后康复专家组成， 神经调节，神经影像学和临床评估。中风后经历疲劳，多达92％的人。 疲劳对身体和心理表现产生负面影响，导致生活质量较低。疲劳也是 在退伍军人社区中的许多其他神经学人群中都存在，例如脑损伤， 多发性硬化症，以及新创造的长卵形现象。知识的进步和 对中风后疲劳的了解可能会导致退伍军人内其他临床人群的进步 社区。第一个目的是测试建立良好的神经调节疗法的影响 经颅磁刺激（RTMS），减轻了势后疲劳的严重程度。预计这个目标 关于从其他神经精神/认知障碍和治疗的研究获得的理论原理 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 RTMS到额叶，左前额外的形成皮层或双侧到运动皮层。这些 在其他神经系统条件下，疲劳中暗示了位置。我希望显示RTM可以习惯 减少冲程后疲劳的严重程度。但是，治疗的有效性和位置可能部分是 取决于个人特征。该研究的第二个目的是基于技能和知识 我计划在CDA-1中开发，以鉴定疲劳的其他神经生理生物标志物。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谷氨酸能活动/信号 有或没有中风后疲劳。我希望表明疲劳组将显示谷氨酸能功能障碍， 通过物质内设施中的较大不对称和对配对联想的促进响应来衡量 刺激，与非竞争者组相比。将谷氨酸和相关代谢产物鉴定为一种 导致中风后疲劳的病理生理贡献者可能有助于开发新的治疗方法 在其他神经系统条件下进行中风后疲劳和疲劳。