DEDICATIONI would like to dedicate this dissertation to my best friend and the love of my life Andres and to my precious children Benjamin and Jeremias.They are the center of my universe. 111 ACKNOWLEDGEMENTSI would like to express my greatest gratitude to my mentor Dr. Susan Harkema, who gave me a lifetime opportunity in allowing me to work with her. Dr. Harkema not only gave me guidance and the tools to conduct my investigation; but also she gave me independence to explore and explode my own potential. I have learned in the past five years more than many would in their lifetime. She allowed me to truly understand that the main reason behind sciences is to improve people's life; translating lab findings to the clinic, giving hope and alleviating the pain of many who are suffering. Pulmonary complications associated with persistent respiratory muscle weakness and paralyses are critical problems faced by patients with chronic spinal cord injury (SCI). The aim of this dissertation is to investigate the role of neurological injury and neural plasticity on pulmonary function after SCI in humans. We tested the following hypotheses: 1) post-SCI respiratory insufficiency is related to the severity of the spinal lesion; 2) respiratory insufficiency is related to abnormal neuromuscular activity of respiratory muscles and that the electromyographic (EMG) amplitude of respiratory muscles is correlated to respiratory muscle strength and 3) locomotor training, an activity-based therapy, improves pulmonary function in individuals with cervical and upper thoracic SCI. We recorded standard sitting spirometry in SCI (n=35) and noninjured individuals (n=15). We also recorded EMG patterns from inspiratory, expiratory and accessory muscles during maximal respiratory pressures maneuvers. Motor incomplete SCI subjects have significantly higher pulmonary function than motor complete (p = 0.006). The respiratory muscle activation patterns were variable in SCI during all maneuvers. VI After SCI, neural plasticity results in a compensatory recruitment of nonrespiratory muscles for pulmonary function. Higher maximal inspiratory pressure (MIP) is related to higher EMG activity of the upper trapezious in the cervical incomplete group, suggesting that this muscle is being successfully recruited to create higher inspiratory pressure. EMG activity of the latissimus dorsi is negatively correlated with maximal expiratory pressure (MEP) in both cervical motor complete and incomplete subjects, suggesting that this muscle is being recruited as a compensatory strategy for forced expiration in individuals with cervical SCI. Locomotor training is a beneficial intervention for improving pulmonary function in SCI individuals. These findings can improve our understanding of the mechanisms that underlie respiratory insufficiency and may be useful to develop objective, quantitative evaluation of the neural control of respiration after neurologic injury.VB