Respiratory dysfunction is the leading cause of death in individuals with spinal cord injuries (SCIs). Nearly one quarter of all SCI cases involve injury to the upper spinal cord segments which impairs neural activation of the diaphragm muscle and compromises breathing. Although mechanical ventilation can be life-saving after cervical SCI (C-SCI), it also triggers rapid and profound diaphragm muscle atrophy, thereby complicating (or even preventing) ventilator weaning. Intramuscular diaphragm stimulation, or diaphragm pacing, was developed to replace long-term ventilator support, and is now used acutely post C-SCI (<4 months following injury) to promote ventilator weaning. The impact of diaphragm pacing on respiratory function and diaphragm muscle activation has not been formally evaluated. This is an essential step in determining the efficacy of intramuscular diaphragm stimulation and its effects on respiratory function after SCI. Accordingly, this research study will evaluate the effects of intramuscular diaphragm stimulation and test the hypothesis that diaphragm pacing enhances neuromuscular diaphragm activation and respiratory function in adults with cervical SCIs. The investigators will test the hypothesis by evaluating the effects of diaphragm pacing on neuromuscular activation of the diaphragm by directly recording electromyogram (EMG) activity from the intramuscular pacing electrodes. Recording from these surgically-implanted electrodes allows direct comparisons of EMG activity across time, minimizing methodological limitations inherent with surface or percutaneous EMG recordings. This approach, in association with respiratory assessments, will be used to investigate the impact of diaphragm pacing in adults with intramuscular diaphragm pacing electrodes following acute, traumatic C-SCIs.

Subject recruitment. Patients with acute, traumatic C-SCIs, scheduled to receive intramuscular diaphragm pacing OR who have recently received a diaphragm pacer (within past 5-days) will be recruited from two Level-1 trauma hospitals serving North Florida - UF Health Shands Hospitals in Gainesville and Jacksonville, Florida.

Enrollment. Patients with acute, traumatic C-SCIs (AIS A-C, affecting C1-C6 segments) who are scheduled to undergo or who have recently received implantation of diaphragm pacing electrodes (within recent 5-days) will be identified by the investigators.

After obtaining informed consent for participation in the study, members of the study team will review the participant's medical records to obtain study-related data and verify that the participant meets the study criteria. Clinical tests of sensory and motor function also may be conducted to verify the participant's SCI classification and extent of SCI. The tests of sensory and motor function are part of the American Spinal Injury Association (ASIA) Impairment Scale and the International Standards for Neurological Classification of Spinal Cord Injury. These clinical assessments are part of standard clinical care and include tests of sensation (dermatomes) and muscle strength via manual muscle testing (myotomes). These tests are done to clinically determine which segmental levels of the spinal cord demonstrate normal or impaired function. These tests also aid in determining if the SCI is clinically complete or incomplete. Determination of complete versus incomplete is based on the sensory and motor function in the lowest sacral segments which control sensation and motor function at the anal sphincter. Respiratory function will be assessed by measurement of maximal expiratory pressures and standard spirometry (tidal breathing, maximal voluntary ventilation and flow-volume curves).

Following enrollment and implantation of diaphragm pacing electrodes, individuals will be assessed at regular intervals. Assessments will include: a.) clinical ASIA neurologic examination of sensory and motor function (as described above) b.) recording of intramuscular diaphragm EMGs c.) measurement of diaphragm muscle strength via standard clinical assessment of maximal inspiratory pressures and d.) standard clinical measures of respiratory function.

Up to 5 assessments will be conducted in the acute hospital setting; up to 5 assessments during inpatient rehabilitation (Brooks Rehabilitation); up to 4 assessments will be conducted after discharge to the home setting.

ASSESSMENT OVERVIEW: The examination will allow investigators to characterize longitudinal changes in segmental sensory and motor function. Diaphragm electromyogram (EMG) will be recorded from the intramuscular diaphragm pacing electrodes and respiratory function will be assessed during non-stimulated respiration (diaphragm pacing unit turned off). Diaphragm EMGs will be recorded from the intramuscular pacing electrodes with a custom connector that attaches to the external pacing electrode wires and interfaces with an EMG acquisition system. Concurrent with EMG recordings, each assessment will include tests of maximal inspiratory pressures to assess diaphragm muscle strength.

Assessment of the neuromuscular activation of the diaphragm will be performed. Neuromuscular activation of the diaphragm will be assessed by recording diaphragm EMGs from the surgically-implanted intramuscular stimulating electrodes. This approach will allow for comparisons of EMG recordings across time and reduces the methodological limitations associated with surface or percutaneous EMG approaches. EMGs will be recorded during non-stimulated respiration (diaphragm pacer turned off) and simultaneously with assessments of respiratory function. These assessments may include maximal inspiratory pressures; sniff nasal inspiratory pressure, maximal expiratory pressure, assessments of resting tidal breathing, inspiration to total lung capacity, maximal voluntary ventilation and measurement of flow volumes using standard spirometry.

During the assessments, photographs and/or video recordings may be obtained. These recordings will be done with the participant's knowledge and consent for the type of recording being obtained. Photographs and video recordings will be used to communicate study procedures with the study team and to monitor the assessment process. Video and photographic data will be used to assess how individuals with SCIs perform and respond to the testing and to communicate the study procedures. Video and photographic information will be used in a manner based on the level of consent obtained from each participant.

Primary outcomes to characterize neuromuscular activation of the diaphragm and assess changes in diaphragm activation associated with intramuscular diaphragm stimulation will include: amplitude and timing characteristics (raw, filtered EMGs and normalized); neural respiratory drive to evaluate diaphragm muscle activation during tidal breathing relative to activation capacity during maximal inspiratory maneuvers; and time-frequency characteristics of the diaphragm EMGs (wavelet analysis).

Inclusion Criteria:

• Acute, traumatic cervical spinal cord injuries (C-SCIs), classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) as A-C (complete SCI (A); motor complete SCI (B); motor incomplete with minimal motor function (C)), affecting C1-C6 spinal cord segments
• Scheduled to undergo implantation of a diaphragm pacer, or who have recently received (in past 5-days) implantation of intramuscular diaphragm pacing electrodes due to severe respiratory impairments and dependence on mechanical ventilation.

Exclusion Criteria:

• Progressive neuromuscular diseases such as multiple sclerosis and myasthenia gravis
• History of neurologic injuries such as stroke or prior SCI
• Chest wall injuries or deformities likely to influence breathing
• Pulmonary infection
• Pregnancy
• Cognitive impairments limiting study participation

Forty adults will be recruited from an acute care hospital setting