Grant: Project Grant

Stroke is the leading cause of adult neurological disability with most survivors suffering moderate to severe long-term sensorimotor deficits. These are caused by the incomplete remapping of lost function to surviving neurons. To date, the many attempted pharmacological approaches have shown limited effectiveness in patients, likely due to the difficulty in their delivery, dosing, and their numerous off-target effects. Neuromodulation is a rapidly evolving technology that has recently yielded encouraging results in a variety of neurological conditions because of its flexibility, excellent tolerability, and lack of off-target effects. However, an understanding of its effects on neuronal and brain vascular networks is critical for judicious application of this technology to the continuously-adapting brain. In this project, we will leverage our expertise in invasive electrophysiological recordings and analysis, optogenetic models for cellularly specific neurostimulation, and MRI assessment of the coupling between neuronal activity and brain blood flow in a finely controlled preclinical model of ischemia to map changes in brain function elicited by transcranial current stimulation. We will tune the stimulation parameters so as to normalize the coupling between distinct neuronal oscillations and their signaling to brain vessels in the chronic stage following stroke. These studies will lay the foundation for development of personalized noninvasive transcranial current stimulation for targeting functional deficits following ischemic stroke.