Research: Stroke remains the leading cause of motor disability in the United States. There is a growing body of evidence suggesting that electrical stimulation to multiple brain areas can promote motor recovery. Such stimulation is shown to be beneficial when applied near the injury, or to distant areas, or to multiple regions together. However, the vast majority of this research has used `open-loop stimulation' (OLS) methods, where stimulation is grossly turned on and off over long-periods of time and the results have shown marginal or inconsistent improvements. In contrast, `closed-loop stimulation' (CLS) aims to deliver stimulation during brief periods of time only in response to specific states. Given that neural activity and brain states are highly non-stationary, CLS may be more physiological in that it can be used to promote states that are associated with adaptive plasticity. To implement a CLS, we need to determine the brain states that are best to trigger CLS and will promote plasticity. Mentored Phase: The objective of this proposal during the mentored K99 phase is: (1) to find brain states that can serve as optimal triggers for CLS, and (2) to test if CLS to perilesional cortex promotes recovery better than OLS. I have conducted pilot experiments using multielectrode recordings and stimulation in awake behaving rodents to better understand the neural states that can both induce plasticity and promote motor recovery after stroke (using different stroke models). My preliminary data indicates that neural synchrony in the β-band (12-30 Hz) may be an important trigger for stimulation. I will test the effects of CLS triggered by rise in synchrony in the β-band. Independent Phase: In severe strokes, concurrent stimulation to two motor areas may be better at enhancing cortical excitability. Furthermore, in order to optimize the benefits of CLS, it is important to understand how CLS works. In the independent phase, I will test: (3) the effects of a combined CLS to perilesional cortex and contralesional cerebellum; and (4) the enhanced excitability of M1 cells as the causal substrate of CLS mediated recovery using optogenetic tools. These experiments will combine state-of-the-art multi-resolution electrophysiological monitoring (i.e. spikes, local-field potential, and electrocorticography) with a rodent model of stroke. While this proposed experimental approach is in rodents, using these multiple levels of monitoring, I also seek to identify alternate biomarkers that might be identified through less invasive means (e.g. only using electrocorticography). If successful, these experiments will identify important electrophysiological biomarkers that can be implemented in clinically relevant CLS for stroke recovery. Candidate: my broad interests are in using neural engineering tools for rehabilitation after brain and spinal cord injury. My long-term goal is to become an independent investigator with a lab that combines advanced systems electrophy...