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Hyperoxia also provokes hyperventilation, which leads to hypocapnia. Although hypocapnia may amplify hyperoxia-induced reductions in CBF and CDo\n                    <jats:sub>2<\/jats:sub>\n                    , its effects on brain oxygen extraction (OEF) and metabolism ([Formula: see text]) remain unclear. We examined how hyperoxia-induced hypocapnia influences CBF, OEF, and [Formula: see text] in humans. Although both isocapnic and poikilocapnic hyperoxia reduced CBF and CDo\n                    <jats:sub>2<\/jats:sub>\n                    , only poikilocapnic hyperoxia increased OEF. [Formula: see text] decreased solely in isocapnic hyperoxia, highlighting hypocapnia\u2019s role in regulating cerebral metabolism.\n                  <\/jats:p>","DOI":"10.1152\/japplphysiol.00354.2025","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:46:05Z","timestamp":1751366765000},"page":"287-295","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of the human brain oxygen extraction fraction and metabolic rate in response to hyperoxia: the role of hypocapnia"],"prefix":"10.1152","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-3139","authenticated-orcid":false,"given":"Marcos P.","family":"Rocha","sequence":"first","affiliation":[{"name":"University of Copenhagen","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7377-9348","authenticated-orcid":false,"given":"Joao D.","family":"Mattos","sequence":"additional","affiliation":[{"name":"Fluminense Federal University","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9526-0937","authenticated-orcid":false,"given":"Monique O.","family":"Campos","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-9910","authenticated-orcid":false,"given":"Daniel E.","family":"Mansur","sequence":"additional","affiliation":[{"name":"Fluminense Federal University","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7045-1329","authenticated-orcid":false,"given":"Qudus A.","family":"Ojikutu","sequence":"additional","affiliation":[{"name":"Purdue University","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels H.","family":"Secher","sequence":"additional","affiliation":[{"name":"University of Copenhagen","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-2886","authenticated-orcid":false,"given":"Antonio C. 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