Spinal cord injuries (SCIs) produce motor impairments that have devastating consequences for the independence and quality of life of affected individuals. These impairments result from the weakening of connections between the cerebral cortex and the spinal cord. Therefore, there is an ongoing need to develop interventions that strengthen corticospinal connections post SCI. Our laboratory focuses on a hybrid intervention that combines intraspinal neuromodulator delivery with use-dependent physical rehabilitation, which increases motor performance after SCI. However, the mechanisms behind this recovery remain relatively unexplored. Our project aims to address this knowledge gap by using evoked potentials (EPs) as biomarkers to quantify the strength of neuronal connections. EPs represent electrical responses in the brain to stimuli. Following a stimulus event, measuring the EP amplitude allows us to assess the strength of neuronal connections. For our experiment, we will implant chronic cortical and spinal microwire arrays in adult rats with chronic cervical SCI and conduct weekly recording sessions before, during, and after a 6-week therapy period. We will then compare changes in the size of EPs recorded during these sessions. We will also assess motor recovery through behavioral scores on a forelimb reach-and-grasp task, which the cervical cord injury directly impairs. We hypothesize that our interventions will strengthen corticospinal connections damaged by the injury, as manifested in a correlation between an increase in EP amplitudes and changes in motor performance. Ultimately, results from our experiments will help us understand how physical rehabilitation and targeted delivery of neuromodulators mediate recovery of the damaged central nervous system. We also hope our project will inform future rehabilitation strategies targeting SCI.

In the United States, 296,000 people live with spinal cord injury (SCI)1. SCI is one of the most debilitating neurological conditions due to the crucial role played by the spinal cord in everyday life. The current treatments for SCI involve invasive surgeries, such as spinal laminectomies and decompressions, which are often paired with non-invasive therapies, such as medications and physical rehabilitation. Despite major innovations in medicine, regeneration of central nervous system (CNS) neurons remains challenging. As a result, reorganization and adaptation, promoted by current therapies, play key roles in recovery after CNS damage with physical rehabilitation being the gold standard of treatment after SCI. Recent SCI research in our laboratory has focused on development of neural interfaces for targeted, intraspinal delivery of plasticity-enhancing neuromodulators, such as brain-derived neurotrophic factor and serotonin. In these experiments, neuromodulator delivery was paired with use-dependent physical rehabilitation on a forelimb reach-and-grasp behavior that is directly impaired by the cervical SCI. We found that our combined intervention promoted greater forelimb-motor recovery compared to physical training alone. However, there were variabilities in the recovery profiles across animals with similar injuries within the same intervention group. Low levels of motivation can lead to less engagement in physical therapy and may be contributing to the observed variabilities. The purpose of this study is to assess motivation levels in spinal-cord injured rats to understand how it affects forelimb-motor recovery given our interventions. Motivation levels will be assessed before, during, and after therapy to examine its influence on motor recovery. We will also assess how SCI and motor recovery impact animal motivation. Preliminary analysis in 6 adult female rats, whose motivation levels were compared before and after injury, shows that SCI lowers motivation (t(5) = 3.052, p = .03, paired samples t-test). Experiments in additional rats are currently ongoing.