RR&D Research Career Scientist Award Application

科学已经成为多学科和综合性的，通常需要研究团队。我在我的职业生涯中 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。在过去五年中 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 研究。这份续签申请是为了继续建设一个个人和机构的神经康复 研究计划以多学科协作研究为基础，涉及临床医生、工程师和 基础科学家。我的最终个人研究目标是翻译和个性化创新康复 这将通过更好地理解运动和运动的基本概念来实现 制定基于机制的康复干预措施和措施： 运动的基本概念：了解行走的任务机制和神经控制 至关重要。早期的工作包括使用肌肉骨骼模型对步行过程中的肌肉功能进行原创性研究 基于计算机模拟，包括第一篇确定单个足底屈肌功能的论文 和一篇有影响力的两部分评论文章。我们还发表了几项使用模拟和 肌肉骨骼建模了解偏瘫患者行走协调性以确定病因 以及特定协调缺陷和由此导致的行走功能限制之间的影响关系。 基于机制的康复：我康复研究的一个基本宗旨是需要机制- 以干预为基础，即了解确切的限制性损害以及不同的干预或 干预的参数会影响这些损伤。我们研究了对运动的反应。 中风后的训练，以确定有反应和无反应的不同特征。我现在也是 探索神经调节以增强康复的潜力。近期的一份重要出版物 确定了中风患者通常的tdcs剂量可以安全地加倍，而另一项研究 建立了上肢运动恢复研究的剂量反应。此外，我还参加了一个 迷走神经刺激用于卒中后康复的多点临床试验。 基于机制的测量：虽然我的研究重点是了解潜在的机制，但我 一直在寻求通过开发由那些基础知识提供信息的度量来翻译这项工作 机械装置。值得注意的例子包括“偏瘫推进”，它衡量对总量的贡献 偏瘫腿所产生的推进力，以及“运动复杂性”，它量化了 独立的协同激活协同作用(或模块)存在于瘫痪的腿部。最近的合作增加了 成像生物标记物，如皮质脊髓束损伤负荷。我目前的退伍军人荣誉奖调查了 皮质网状通路的完整性，使行走适应新的目标(即，加速、减速、转弯)。 我的研究计划通过三个目标为退伍军人管理局的研究做出贡献，并影响退伍军人医疗保健： 1.建立退伍军人康复研究计划。我通过竞争康复资金来做到这一点 通过广泛的指导努力，建立研究基础设施并培训下一代科学家。 2.开展创新研究。我有一个如上所述的创新研究计划。 3.与科学家和临床医生合作。我开发了作为基础的实验室 拉尔夫·H·约翰逊退伍军人康复研究计划的人类受试者部分。这些状态- 先进的实验室提供对运动捕捉和其他神经力学数据收集的访问； 神经调节和TMS神经生理学；以及用于康复应用的高密度脑电。

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.