Electrical Neuromodulation of the Respiratory System After Spinal Cord Injury  Jan T. Hachmann, MD, MS, Peter J. Grahn, PhD, Jonathan S. Calvert, BS, Dina I. Drubach, DSc, PT, Kendall H. Lee, MD, PhD, Igor A. Lavrov, MD, PhD  Mayo Clinic Proceedings  Volume 92, Issue 9, Pages 1401-1414 (September 2017) DOI: 10.1016/j.mayocp.2017.04.011 Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Neurophysiological basis of inspiration and epidural stimulation for restoration of inspiratory function. Each hemidiaphragm is innervated by its ipsilateral phrenic nerve (primarily C3-C5 spinal levels), and the inspiratory external intercostal muscles are innervated segmentally by their respective intercostal nerves. A hypothetical target location for the epidural electrode is shown for upper thoracic spinal cord stimulation on the basis of reviewed literature. Epidural stimulation of the upper thoracic spinal segments (eg, T2 level) can recruit the multilevel inspiratory intercostal muscles to achieve inspiratory airflow. The green arrows depict expansion of the thoracic wall generated by contraction of the external intercostal muscles. In addition, an intercostal-to-phrenic reflex pathway may exist to coordinate diaphragm cocontraction via the phrenic nerve. The blue arrow depicts concomitant diaphragm contraction for expansion of the thoracic cavity and generation of the physiological negative intrathoracic pressure to generate inspiratory airflow. Mayo Clinic Proceedings 2017 92, 1401-1414DOI: (10.1016/j.mayocp.2017.04.011) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Hypothesized neuronal circuits mediating evoked respiratory output of high-frequency spinal cord stimulation. Stimulation of the upper thoracic spinal cord may evoke coordination of intercostal pacing via thoracic segmental interneurons facilitated by intercostal-to-intercostal reflexes and by hypothesized ascending intercostal-to-phrenic reflex pathways synapsing onto cervical prephrenic interneurons and phrenic motor neurons for synergistic phrenic costimulation. Mayo Clinic Proceedings 2017 92, 1401-1414DOI: (10.1016/j.mayocp.2017.04.011) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions