RR&D Research Career Scientist Award Application

科学已经成为多学科和综合性的，往往需要研究团队。我的职业生涯 与临床医生、工程师和基础科学家合作并指导他们发展团队。过去五 多年来，我特别专注于创建基础设施和协作，以促进多学科团队 research.此更新申请是为了继续建立一个个人和机构神经康复 研究计划以合作，多学科研究为基础，涉及临床医生，工程师和 基础科学家我个人的最终研究目标是翻译和个性化创新康复 干预，这将通过更好地理解运动的基本概念和 制定基于机制的康复干预措施和措施： 运动的基本概念：理解行走的任务机制和神经控制是 至关重要的.早期的工作包括使用肌肉骨骼模型对行走过程中肌肉功能的原始研究 基于计算机模拟，包括第一纸确定个人跖屈肌的功能 和一篇有影响力的评论文章我们还发表了几项使用模拟和 肌肉骨骼模型，了解偏瘫步行的协调性，以建立原因 并影响特定协调缺陷与导致的行走功能限制之间的关系。 基于机制的康复：我的康复研究的一个基本原则是需要机制- 基于干预，即，了解确切的限制性损伤以及不同的干预措施或 干预的参数可以影响这些损伤。我们已经研究了对运动的反应 中风后训练，以确定反应者和非反应者的不同特征。我现在也是 探索神经调节增强康复的潜力。最近出版的一本重要书 在中风患者中，通常的tDCS剂量可以安全地加倍，而第二项研究 建立了上肢运动恢复研究的剂量反应。此外，我参加了一个 迷走神经刺激用于中风后康复的多中心临床试验。 基于机制的测量：虽然我的研究集中在理解潜在的机制， 我一直在寻求通过开发由那些基础知识所告知的测量来转化这项工作。 机制等值得注意的例子包括“麻痹性推进”，它测量了对总的 由麻痹腿引起的推进，以及“运动复杂性”，它量化了 独立的协同作用（或模块）存在于麻痹腿。最近的合作增加了 成像生物标志物，如皮质脊髓束损伤负荷。我目前的VA优点调查的重要性， 用于使行走适应新目标的皮质网状通路完整性（即，加速、减速、转弯）。 我的研究计划有助于VA研究，并通过三个目标影响退伍军人医疗保健： 1.建立VA康复研究计划。我通过争取康复资金来做到这一点 研究基础设施和通过广泛的指导工作培训下一代科学家。 2.进行创新研究。我有一个创新的研究计划，如上所述。 3.与科学家和临床医生合作。我建立了实验室， 拉尔夫·H·约翰逊退伍军人康复研究计划的人类受试者组成部分。这些国家- 最先进的实验室提供动作捕捉和其他神经力学数据收集; 神经调节和TMS神经生理学;以及用于康复的高密度EEG。

Science has become multidisciplinary and integrative, often requiring research teams. I have spent my career working with and mentoring clinicians, engineers and basic scientists to develop teams. Over the past five years I have especially focused on creating infrastructure and collaborations to facilitate multidisciplinary team research. This renewal application is to continue building an individual and institutional neurorehabilitation research program grounded in collaborative, multidisciplinary research involving clinicians, engineers and basic scientists. My ultimate individual research goal is to translate and individualize innovative rehabilitation interventions, and this will be achieved through better understanding fundamental concepts of locomotion and developing mechanism-based rehabilitation interventions and measurements: Fundamental concepts of locomotion: Understanding the task mechanics and neural control of walking is crucial. Early work included original studies of muscle function during walking using musculoskeletal model based computer simulations, including the first paper determining the function of the individual plantarflexors and an influential two-part review article. We also published several studies that use simulation and musculoskeletal modeling to understand the coordination of hemiparetic walking in order to establish cause and effect relationships between specific coordination deficits and resulting functional limitations in walking. Mechanism-based rehabilitation: An underlying tenet of my rehabilitation research is the need for mechanism- based intervention, i.e., understanding the exact limiting impairments and how different interventions or parameters of an intervention can affect those impairments. We have studied the response to locomotor training post-stroke to determine the different characteristics of responders and non-responders. I am also now exploring the potential for neuromodulation to augment rehabilitation. An important recent publication established that the usual tDCS dose could be safely doubled in stroke patients, while a second study established a dose response for upper-extremity motor recovery studies. Additionally, I am participating in a multisite clinical trial of vagus nerve stimulation for post-stroke rehabilitation. Mechanism-based measurement: While my research has focused on understanding underlying mechanisms, I have consistently sought to translate that work by developing measurements informed by those underlying mechanisms. Notable examples include “paretic propulsion,” which measures the contribution to total propulsion resulting from the paretic leg, and “locomotor complexity,” which quantifies the number of independent coactivation synergies (or modules) present in the paretic leg. Recent collaborations have added imaging biomarkers like corticospinal tract lesion load. My current VA Merit investigates the importance of corticoreticular pathway integrity for adapting walking to new goals (i.e., speeding up, slowing down, turning). My research program contributes to VA research and impacts veteran healthcare through three aims: 1. Build VA rehabilitation research program. I do this through competing for funding of rehabilitation research infrastructure and training the next generation of scientists through extensive mentoring efforts. 2. Perform innovative research. I have an innovative research program as described above. 3. Collaborate with scientists and clinicians. I developed the laboratories that serve as the foundation for the human subject component of the Ralph H Johnson VA rehabilitation research program. These state-of- the-art laboratories offer access to motion capture and other neuromechanics data collections; neuromodulation and TMS neurophysiology; and high-density EEG for applications for rehabilitation.