Spinal cord injury (SCI) affects the lives of over 294,000 individuals in the United States alone. Therefore, there is an urgency for development of therapies for SCI. We are exploring the role of environmental enrichment in promoting motor recovery from chronic cervical SCI that produces partial to complete forelimb paralysis in adult rats. Novelty, a major component of our environmental enrichment, has been associated with memory consolidation which could be related to the release of plasticity-related products (PRPs). PRPs are a key component of lasting plasticity changes in vitro, which could prove to be vital to motor learning after spinal cord injury. Throughout a 6-week therapy period during which the rats are exposed to environmental enrichment, motor function of the impaired forelimb is assessed using behavioral scores on a reach-and-grasp pellet-retrieval task. Our project will utilize environmental enrichment to enhance the effectiveness of our physical training paradigm. Environmental enrichment will include access to toys that provide opportunities for physical exercise, socialization, and social learning. The toys will be changed each week to promote novelty. We predict that environmental enrichment will have an additive effect in promoting recovery of the impaired forelimb when combined with physical therapy. We hope these results will help inform how neural plasticity can be deployed for design of effective therapies for promoting motor recovery after chronic SCI.

Motor injuries, such as stroke and spinal cord injury, are some of the leading causes of long-term disability and death worldwide. Patients are often left behind with debilitating consequences, such as paralysis or severe motor impairments, creating an urgent need for new therapies to be developed. A treatment option that is gaining momentum is the use of electrical stimulation to strengthen neural pathways for improving motor function of affected individuals. Towards this goal, I have investigated a novel electrical-stimulation paradigm called movement-triggered theta-burst stimulation (MT-TBS) to modulate neuronal connectivity in the motor cortex of macaque monkeys. To implement MT-TBS, a monkey is trained to perform a target-tracking task that activates wrist muscles involved in flexion and extension. While the monkey performs the task, sites in the motor cortex associated with wrist flexion or extension simultaneously receive theta burst stimulation; hence the movement triggers stimulation of cortical sites in this closed-loop system. After receiving MT-TBS, monkeys continue to perform the same target-tracking task on the days following conditioning. Early results show that 50% larger gains in cortical connectivity can be achieved on the same day of conditioning with open-loop TBS. This may indicate that MT-TBS may be an even better method for strengthening connections in the motor cortex. For my research project, I investigated the effects of MT-TBS on changes in the strength of neuronal connections in the motor cortex when coupled with repetition of the conditioned movement in the days following stimulation. In a series of experiments, MT-TBS was delivered during flexion, extension and with the muscle at rest. If successful, pairing MT-TBS with physical rehabilitation will serve as an effective strategy for aiding individuals with motor impairments.