Document Type

Article

Publication Date

7-1-2026

Comments

This article is the author’s final published version in Journal of Neurophysiology, Volume 136, issue 1, 2026, Pages 215-225.

The published version is available at https://doi.org/10.1152/jn.00120.2026. Copyright © 2026 The Authors.

 

Abstract

Respiratory impairment is a leading cause of morbidity and mortality after spinal cord injury (SCI), highlighting the need for interventions that improve breathing function. In people with SCI, acute intermittent hypoxia (AIH) elicits respiratory motor plasticity and improves inspiratory function. However, in uninjured people facilitation of corticospinal diaphragm motor evoked potential (MEP) amplitude occurs only when AIH is combined with mild hypercapnia (acute intermittent hypercapnic hypoxia; AIHH). It remains unclear whether AIHH similarly enhances diaphragm corticospinal excitability after SCI. We tested the hypothesis that AIHH increases diaphragm MEP amplitude and reduces MEP onset latency in individuals with chronic SCI, whereas AIH and sham treatment have little effect. Ten individuals with chronic cervical or high thoracic SCI (6 cervical injuries; 6 classified as motor complete) completed a randomized, double-blind, crossover study with >1-wk washout between interventions. Each intervention consisted of fifteen 1-min episodes of AIH (9% inspired O2), AIHH (9% O2 þ 5% CO2), and sham treatment (21% O2), separated by 1.5-min normoxic intervals. Bayesian hierarchical modeling demonstrated a 99% probability that both AIH and AIHH increased diaphragm MEP amplitude, with no change following sham treatment. AIHH showed consistent evidence of reduced diaphragm MEP latency, consistent with enhanced corticospinal transmission, whereas AIH demonstrated a similar but more uncertain reduction. These findings demonstrate that AIH increases diaphragm corticospinal excitability after chronic SCI and that the addition of mild hypercapnia may further enhance plasticity. Thus, both AIH and AIHH represent feasible, noninvasive strategies to enhance respiratory motor plasticity and potentially improve breathing function after SCI.

NEW & NOTEWORTHY Acute intermittent hypoxia (AIH) with and without hypercapnia elicits cortico-diaphragmatic plasticity in people with chronic SCI. The addition of hypercapnia yields more consistent reductions in motor evoked potential latency, suggesting enhanced corticospinal transmission. These findings differ from observations in uninjured individuals and indicate injury-specific modulation of AIH responsiveness, providing translational insight to refine neuromodulation strategies for improving respiratory motor plasticity after SCI.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

42274776

Language

English

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