Acute intermittent hypoxia (AIH) involves brief (1 min), repeated episodes (~15) of breathing low oxygen air to stimulate spinal neuroplasticity. Animal and human studies show that AIH improves motor function after spinal cord injury, particularly with slightly increased carbon dioxide (hypercapnic AIH; AIHH) and task-specific training. Using a double blind cross-over design, the study will test whether AIHH improves breathing more than AIH and whether specific genetic variations are related to individuals' intervention responses.

This study will consist of two parts - single-session testing days, and respiratory strength training blocks. If a participant is not eligible to enroll in single-day testing, they will be asked to enroll in only the respiratory strength training blocks.

On single-session testing days, participants will be asked to come in on three separate days they will complete a battery of tests, then be given one of three interventions, and then complete the same battery of tests. The three interventions are acute intermittent hypoxia (AIH), acute intermittent hypercapnic-hypoxia (AIHH), or sham acute intermittent hypoxia (sham AIH). These interventions are explained in more detail below.

During respiratory strength training blocks, participants will receive five days of AIH, AIHH, or sham AIH in combination with respiratory strength training, which uses small hand-held devices to strengthen the muscles used for breathing. Participants will be asked to complete all three blocks to receive all three interventions. In addition to 5 days of interventions and respiratory strength training, the respiratory strength training blocks include testing 1 day, 3 days, and 7 days after the 5 days of respiratory strength training.

Inclusion Criteria:

1. Adults 18-70 years of age

2. Chronic incomplete SCI ≥ 1 year at or below C1-T12

   • Incomplete SCI based on residual sensory and motor function below the level of the injury or injury classification of B, C, D at initial screening according to the American Spinal Injury Association Impairment Classification and the International Standards for the Neurological Classification of SCI.

   -OR- Chronic complete SCI ≥1 year at or below C4-T12

   • Complete SCI based on the absence of residual sensory or motor function below the level of injury or injury classification of A at initial screening according to the American Spinal Injury Association Impairment Classification and the International Standards for the Neurological Classification of SCI.

3. Medically stable with physician clearance

4. SCI due to non-progressive etiology

5. 20% impairment in maximal inspiratory, maximal expiratory pressure generation, or both relative to normative values

Exclusion Criteria:

1. Current diagnosis of an additional neurologic condition such as Multiple Sclerosis, Parkinson disease, stroke, or brain injury
2. Severe illness or infection, including non-healing decubitus ulcers, untreated bladder or urinary tract infections, cardiovascular disease, lung disease, active heterotopic ossification, or uncontrolled hypertension
3. Severe neuropathic pain
4. Known pregnancy
5. Severe recurrent autonomic dysreflexia

Exclusion for involvement in TMS - History of seizure disorder, uncontrolled migraines, presence of cardiac pacemaker, metal implants in skull, medications that lower seizure threshold.