The goal of this research study is to evaluate the effects of a single session of rehabilitation in healthy adults, before noninvasive mechanical ventilation (MV). MV can help support breathing function during sleep or illness. High levels of MV support have been reported to alter the function of the diaphragm muscle, the primary breathing muscle, in people with compromised health. However, rehabilitation may have some potential to improve diaphragm function in advance of using MV. This study will test different rehabilitation interventions, including (1) inspiratory strength training (IST), (2) transcutaneous spinal cord stimulation (TSCS), or sham TSCS. Before and after MV, participants will complete breathing strength tests and responses to phrenic nerve stimulation.

Brief periods of mechanical ventilation (MV) can degrade the function of the diaphragm, which can be a problem for older adults and people with multiple medical comorbidities. 20% of people who are placed on MV require a prolonged effort to wean back to independent breathing. The effects of MV on respiratory neural function are often unaddressed by typical clinical practices. Many aspects of clinical practice such as MV, anesthesia, opioid medication directly reduce respiratory neural drive and degrade diaphragm fiber contractile function, and these impairments can occur rapidly, persist after extubation, and increase the risk for postoperative pulmonary complications. These complications delay discharge, incur significant expenses, and place patients at risk for an incomplete recovery and significant morbidity. Thus, any rehabilitation strategies to preserve or improve phrenic/diaphragm motor function have the potential to expedite early post-operative mobilization and reduce the risk of complications.

Inspiratory muscle strength training (IST) is an effective rehabilitation method to strengthen the diaphragm muscle. Repetitive IST reinforces respiratory neuromuscular plasticity, induces diaphragm remodeling, and improves inspiratory strength. Bouts of high intensity inspiratory loading acutely increase respiratory neural drive and potentiates inspiratory motor recruitment. Additionally, in some clinical situations, IST exercise is not feasible, thus another option may be electrical stimulation of the diaphragm/phrenic motor area (C3-C6) to generate similar improvements in inspiratory drive to preserve breathing function.

The central hypothesis of this proposal is that rehabilitation to increase diaphragm excitability in advance of MV will offset post-MV inspiratory dysfunction. To test this hypothesis, a repeated-measures, blinded study of healthy adults without respiratory comorbidities will be recruited. Consenting participants will complete a familiarization session, followed by three separate, two-hour noninvasive MV sessions, one week apart. MV sessions will be preceded by: 1) a single, high-intensity IST session, and 2) transcutaneous spinal cord stimulation, and 3) sham electrical stimulation, in randomized order. Changes in respiratory drive, voluntary and evoked diaphragm strength, and dyspnea will be evaluated. The central hypothesis will be tested with the following aims:

Aim 1: Test the hypothesis that noninvasive, positive pressure ventilation acutely decreases respiratory drive and maximal diaphragm activation during a two-hour MV session and persists up to 24 hours later.

Aim 2: Test the hypothesis that even single rehabilitation sessions (IST, transcutaneous stimulation) in advance of MV will preserve evoked diaphragm recruitment and hasten early recovery from MV, when compared to sham stimulation.

Inclusion Criteria:

Non-smokers Sedentary or recreationally active Normal lung function No history of claustrophobia

Exclusion Criteria:

Current smoking or vaping Obstructive lung disease Use of antibiotics or systemic corticosteroids to treat an acute condition History of sepsis or metastatic disease Post infectious conditions that affect breathing Diagnosed with a neurological or neuromuscular condition Any use of supplemental oxygen, continuous positive airway pressure (CPAP), or other positive pressure ventilation to treat sleep apnea Cardiac disease Orthopedic conditions that impair lung expansion Pregnancy Implanted metallic devices within 10 cm of the cervical spine

Participant data that underlie the results reported in this article after deidentification.

9 months and ending 36 months following article publication.

Investigators whose proposed use of the data has been approved by an independent review committee.