Project Summary/Abstract Respiratory motor control deficit is the leading cause of morbidity and mortality in patients with spinal cord injury. The long-term goal of this research is to develop a rehabilitation strategy for respiration in patients with spinal cord injury as a standard of care. Our previous findings demonstrate that respiratory function in patients with chronic spinal cord injury can be improved by using our original inspiratory-expiratory pressure threshold respiratory training protocol. However, the effectiveness of this intervention is limited by the levels of functional capacity preserved below the neurological level of injury. Our preliminary data obtained for this proposal demonstrate that electrical spinal cord stimulation applied epidurally at the lumbar level in combination with respiratory can activate and re-organize spinal motor networks for respiration. We propose to investigate respiratory motor control-related responses to epidural spinal cord stimulation alone and in combination with respiratory training. By characterization of respiratory muscle activation patterns using surface electromyography in association with pulmonary functional and related cardiovascular measures, we expect to determine specific stimulation parameters needed to increase spinal excitability below level of injury to enhance responses to the input from supraspinal centers that remain after injury and to promote the neural plasticity driven by the respiratory training. This hypothesis will be tested by pursuing two specific aims: 1) Evaluate the acute effects of epidural spinal cord stimulation on respiratory functional and motor control properties; and 2) Evaluate the effectiveness of epidural spinal cord stimulation combined with respiratory training.