The contribution of premotor cortex to recovery after stroke.

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Project Summary/Abstract The goal of this project is to determine how ipsilesional premotor cortex facilitates recovery of motor function after ischemic injury in primary motor cortex. When an individual suffers damage to primary motor cortex, they often experience permanent reductions in motor function, including decreased motor coordination, muscle strength, movement speed and movement accuracy. While some spontaneous recovery can occur during the ensuing weeks to months, functional impairments often persist, leading to a reduction in quality of life and an increase in prolonged medical complications and expenses. Over the past two decades, basic research studies in pre-clinical animal models of brain injury, as well as clinical populations, have suggested that the brain can undergo structural and functional reorganization within and between spared regions. This neuroplasticity is thought to underpin functional recovery, however its manifestation as increases in task-related motor function has yet to be established. We have proposed that when primary motor cortex is damaged through ischemic injury, spared sensorimotor areas can take over some volitional control of motor function, and that the ipsilesional premotor cortex plays the biggest role in this control. In this project, we will investigate the timing and contribution of premotor cortex on both spontaneous motor recovery and recovery facilitated by rehabilitative intervention in a rat model of ischemic injury. First, we will establish the time period when premotor cortex contributions are necessary for spontaneous recovery to occur by temporarily inactivating premotor cortex after the ischemic injury (Aim 1). We will then determine if the task-related activity within premotor cortex is altered following the injury, whether these alterations impact the population level encoding of these tasks, the role rehabilitation has in shaping any novel task related activity and, if PM is inactivated, if task-related motor encoding occurs in other cortical areas (Aim 2). Finally, we will establish the relationship between the timing of premotor cortex reorganization and the strength of functional connectivity between spared areas using a stimulation-evoked cortical connectivity measurement and then determine if this physiological marker matches the novel anatomical sprouting from premotor cortex that occurs after an ischemic injury (Aim 3). This project is innovative as it uses a within-animal model to assess 1) how different cortical areas reorganize to restore motor function and 2) the impact of rehabilitation therapy on this reorganization. This project has a significant potential health impact, as the elucidation of location, timing and mechanisms related to functional behavioral recovery, especially when coupled to rehabilitative therapy, will create a complete picture of the neural substrates of recovery. This information is critical to maximize existing therapies and give rise to novel applications for the treatment of brain injuries.