Spinal cord injury (SCI) causes life-long neurological impairment, with loss of sensory and motor function distal to the point of injury. There are approximately 300,000 patients living with SCI in the United States, and currently no effective treatment, reducing their quality of life. Amongst other things, proprioception, which has been determined essential for normal locomotion, can be lost with SCI. Epidural Electric Stimulation (EES), that is thought to excite large diameter afferent fibers (LDAF), has been found to improve recovery from spinal cord injury in conjunction with movement rehabilitation in animal models and humans. This represents an exciting new approach to help these patients. However, many open questions remain about how and why EES works. Chief among them are 1) which of the afferent fibers are necessary and sufficient to promote better recovery, and 2) what are the mechanisms of plasticity in the spinal cord that underly improvement. Here, we sought to address the first question by using viral and genetic tools to begin to target specific subsets of LDAF. First, we use a viral vector that preferably transduces only in the large diameter afferent fibers (LDAF) in the Dorsal Root Ganglia (DRG), and then specifically only the proprioceptors within the LDAF, by using a transgenic rat line that expresses Cre recombinase in Parvalbumin, a marker for proprioceptive neurons in the DRG. This approach consists of using the chemogenetic modulator of neuronal activity Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which are activated by a putatively inert drug, clozapine-N-oxide (CNO), that crosses the blood brain barrier. While we were able to specifically target LDAF with excitatory DREADDs in L3-L5 DRGs in wild type rats, we were unsuccessful at specifically targeting proprioceptors by using the Pvalb-iCre rat line. Additionally, we studied the effect of exciting LDAF on rats with a 200KDyn SCI. CNO withdrawal on the week 7 stage of the recovery was associated with worse ladder performance than the previous and following weeks, as well as worse kinematic behavior of the same week on lower speeds in ankle movement. These results suggest that DREADDs activation is necessary for changes in movement at longer times post injury. It does not rule out that plasticity in neural circuitry has occurred but suggests that plasticity may rely on afferent activation. Finally, we sought to develop new methods to overcome skin motion artifact in rat kinematics by tattooing the knee area under the skin and recording infrared high-speed videos of moving rats which would correct joint calculations beyond just triangulation methods, as well as a novel MATLAB application that can accurately and reliably perform automated H-Reflex measurements, test the stimulating electrodes, and carry out typical instantaneous analyses, which in return allows for faster data collection with reduced human error, and subsequently result in higher research quality. / Bioengineering

Although there are thousands of new spinal cord injury cases each year, length of stay in rehabilitation has significantly decreased, leaving individuals with SCI returning to the community unprepared. Empower SCI is a non-profit organization that aims to fix this gap by providing rehabilitation services to community-dwelling adolescents and adults with SCI. The outcome measures currently used at Empower SCI were assessed to determine if they were a good fit for the program based on their items, scoring system, psychometric properties, and effectiveness at capturing change. In addition, a new assessment measure, the SCI-QOL Resilience SF, was piloted with two participants in a case study format to capture an additional important change, resilience, at Empower SCI. The SCI-QOL Resilience Short Form captured significant change in resilience for one out of two participants. However, both participants shared that Empower SCI provided them with new resources to overcome obstacles to occupational participation and a more positive outlook on life after SCI. Recommendations for the continuation, discontinuation, or altered use of all assessment measures were made based on if they fit the needs of Empower SCI participants and the environment. With an improved data collection system, Empower SCI can demonstrate its positive outcomes to key stakeholders and continue expanding its program to new states and countries. / 2022-10-09T00:00:00Z

Perceived exertion is how hard or heavy an individual feels they are working. Perceived exertion is often quantified using the ratings of perceived exertion (RPE) scale and can be used to measure exercise intensity based on the experience of an individual. While objective methods of assessing exercise intensity, such as measurement of heart rate and percent of peak oxygen uptake, are useful, RPE is commonly implemented for the ease of use and feasibility. For example, RPE is commonly implemented in rehabilitation settings for people with a spinal cord injury and individuals with coronary artery disease because of their non-linear heart rate response to increases in exercise workload. The overarching purpose of this dissertation was to investigate a range of research questions designed to advance the knowledge and use of RPE guided exercise. Through a systematic review and meta-analysis, we examined evidence for the impact on cardiorespiratory fitness and peak power output using RPE-guided interventions in individuals with a spinal cord injury (SCI) and found that RPE-guided interventions improved both after a variety of exercise intervention types and lengths. In a separate retrospective cross-sectional analysis, we then demonstrated that perceived exertion, measured by leg cycling effort during a cardiopulmonary exercise test on a leg cycle ergometer in non-disabled individuals, was predicted by power and maximum power output. After further investigation we found that quadriceps strength predicted maximum power output and therefore is related to leg cycling effort. In the third study of the thesis, we conducted semi-structured interviews in individuals with an SCI and their healthcare practitioners and found that individuals commonly described their sensations associated with the 0-10 RPE scale using muscle sensations when both recalling exercise and after the completion of an acute exercise trial on an arm cycle ergometer. Lastly, we investigated the relationship between psychological and physiological measures and RPE during an arm cycling exercise during a maximal graded exercise test, high intensity interval training, and moderate intensity continuous training using a crossover experimental design in both non-disabled individuals and individuals who were mobility impaired due to SCI. While there were no relationships between any variable and RPE in non-disabled individuals, age and triceps strength predicted central RPE and peak feeling scale predicted peripheral RPE in individuals with an SCI. These mixed methods results collectively suggest that muscle strength, not heart rate, is the strongest predictor of perceived exertion especially in clinical populations completing high intensity exercise. Our novel findings suggest that RPE is regulated through a system of psychological and physiological phenomena, strongly related to muscle sensations arising from the working muscle groups and may have utility and relevance in complementing measures of exercise intensity for a broad range of individuals across the spectrum of health and disease. Future studies should examine the use of muscle sensation descriptions as descriptors of exercise intensity prior to the development of high intensity exercise guidelines in clinical populations, such as individuals with SCI. / Thesis / Candidate in Philosophy / It has been well established that heart rate and ratings of perceived exertion are related in young, healthy individuals, however the nuances of the relationships between other contributors and how clinical populations feel during exercise remain unclear. Using mixed methods, this research sought to determine what sensations help people determine how they feel during exercise, with a focus on high intensity interval training exercise. Our results show that muscle strength may be a key determinant in the perception of effort in individuals with a spinal cord injury and in clinical populations during arm and leg maximal graded exercise tests, but the relationships between physiological variables and perceptions of arm effort in non-impaired individuals remains to be determined. Sensations of effort are regulated through a variety of different mechanisms that vary with population, and the relationships depend on the parameters (e.g., exercise modality and intensity) of the exercise. Future studies should be conducted to determine the individual contributions of different body systems to perceived exertion during exercise in a wide range of populations.

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