RR&D Research Career Scientist Award Application

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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.