{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:12:54Z","timestamp":1790485974111,"version":"4.1.0"},"reference-count":79,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL147554"],"award-info":[{"award-number":["R01 HL147554"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Acute intermittent hypoxia (AIH) elicits long\u2010term facilitation (LTF) of respiration. Although LTF is observed when CO<jats:sub>2<\/jats:sub> is elevated during AIH in awake humans, the influence of CO<jats:sub>2<\/jats:sub> on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic\u2010hypoxia (AIHH): (1) enhances cortico\u2010phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic\u2010normoxia (Sham). Protocols consisted of 15, 60\u00a0s exposures with 90\u00a0s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor\u2010evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (<jats:italic>P<\/jats:italic><jats:sub>0.1<\/jats:sub>), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30\u201360\u00a0min after exposures. Increases in TMS\u2010evoked diaphragm potential amplitudes were observed following AIHH <jats:italic>vs<\/jats:italic>. Sham (+28\u00a0\u00b1\u00a041%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003), but not after AIH. No changes were observed in CMS\u2010evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21\u00a0\u00b1\u00a034%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The occurrence of respiratory long\u2010term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO<jats:sub>2<\/jats:sub> regulation \u2013 mechanisms governing the critical role of CO<jats:sub>2<\/jats:sub> have seldom been explored.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We tested the hypothesis that acute intermittent hypercapnic\u2010hypoxia (AIHH) enhances cortico\u2010phrenic neurotransmission in awake healthy humans.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The amplitude of diaphragmatic motor\u2010evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mouth occlusion pressure (<jats:italic>P<\/jats:italic><jats:sub>0.1<\/jats:sub>, an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long\u2010term facilitation in awake humans.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp282822","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T11:11:50Z","timestamp":1648552310000},"page":"2515-2533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Acute intermittent hypercapnic\u2010hypoxia elicits central neural respiratory motor plasticity in humans"],"prefix":"10.1113","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-7113","authenticated-orcid":false,"given":"Joseph F.","family":"Welch","sequence":"first","affiliation":[{"name":"Breathing Research and Therapeutics Centre University of Florida  Gainesville FL USA"},{"name":"Department of Physical Therapy University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayakrishnan","family":"Nair","sequence":"additional","affiliation":[{"name":"Breathing Research and Therapeutics Centre University of Florida  Gainesville FL USA"},{"name":"Department of Physical Therapy University of Florida  Gainesville FL USA"},{"name":"Department of Physical Therapy Thomas Jefferson University  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Argento","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Engineering University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-1861","authenticated-orcid":false,"given":"Gordon S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Breathing Research and Therapeutics Centre University of Florida  Gainesville FL USA"},{"name":"Department of Physical Therapy University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Fox","sequence":"additional","affiliation":[{"name":"Breathing Research and Therapeutics Centre University of Florida  Gainesville FL USA"},{"name":"Department of Physical Therapy University of Florida  Gainesville FL USA"},{"name":"Brooks Rehabilitation  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009485"},{"key":"e_1_2_6_3_1","first-page":"709","article-title":"Long\u2010term facilitation of ventilation in humans during NREM sleep","volume":"21","author":"Babcock M. 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