{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:46:12Z","timestamp":1792158372590,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Abstract<\/jats:title>\n \n During running, cerebral blood flow (CBF) does not exhibit the inverted\u2010U response observed during cycling; instead, CBF increases up to maximal exercise, despite reductions in end\u2010tidal CO\n 2<\/jats:sub>\n (). The mechanism(s) driving this divergent response are unknown but may relate to foot strike\u2010induced pulsatility oscillations and\/or reductions in cerebrovascular CO\n 2<\/jats:sub>\n reactivity (CVR). We assessed middle cerebral artery blood velocity (MCA\n v<\/jats:sub>\n ), and MCA\n v<\/jats:sub>\n pulsatility variability during an incremental running test (\n n<\/jats:italic>\n \u00a0=\u00a043) and fixed workload exercise under two conditions (\n n<\/jats:italic>\n \u00a0=\u00a017): (1) free running and (2) diastolic stepping, where the foot\u2010strike was synced to the diastolic phase of the cardiac cycle. CVR was assessed (\n n<\/jats:italic>\n \u00a0=\u00a012) at rest and during running. Young, healthy males and females exhibited progressive increases in the MCA\n v<\/jats:sub>\n mean during incremental running (Females, Rest: 49.9\u00a0\u00b1\u00a011.3\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n , : 65.7\u00a0\u00b1\u00a011.7\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n ; Males, Rest: 45.9\u00a0\u00b1\u00a010.8\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n , : 67.1\u00a0\u00b1\u00a013.0\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n ; ANOVA\n P\u00a0<\/jats:italic>\n <\u00a00.0001) despite reductions in at higher intensities (Females, Rest: 36.41\u00a0\u00b1\u00a05.1\u00a0mmHg, : 28.2\u00a0\u00b1\u00a05.1\u00a0mmHg; Males, Rest: 38.6\u00a0\u00b1\u00a04.5\u00a0mmHg; : 32.5\u00a0\u00b1\u00a09.0\u00a0mmHg; ANOVA\n P\u00a0<\/jats:italic>\n <\u00a00.0001). Diastolic stepping removed pulsatility oscillations, reducing MCA\n v<\/jats:sub>\n pulsatility variability (0.14\u00a0\u00b1\u00a00.04\u00a0mmHg), compared with free running (0.29\u00a0\u00b1\u00a00.09\u00a0mmHg,\n P\u00a0<\/jats:italic>\n <\u00a00.0001). However, the MCA\n v<\/jats:sub>\n mean was not different (56.1\u00a0\u00b1\u00a08.1\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n vs<\/jats:italic>\n . 58.0\u00a0\u00b1\u00a08.7\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n ;\n P\u00a0=\u00a0<\/jats:italic>\n 0.211). CVR to hypocapnia decreased from rest to running (\u22120.79\u00a0\u00b1\u00a00.44\n vs<\/jats:italic>\n . \u20100.19\u00a0\u00b1\u00a00.50\u00a0cm\u00a0s\n \u22121<\/jats:sup>\n \u00a0mmHg\n \u22121<\/jats:sup>\n ;\n P\u00a0=\u00a0<\/jats:italic>\n 0.006). Additional experiments found that hypocapnic CVR progressively decreased with increasing exercise intensity (ANOVA\n P<\/jats:italic>\n \u00a0=\u00a00.0065), related to the increase in arterial pressure, but was similar during running and cycling when arterial pressure was matched (\n P<\/jats:italic>\n \u00a0=\u00a00.999). These findings demonstrate that the CBF response during intense exercise is related to the prevailing arterial pressure and not modality\n per se<\/jats:italic>\n , likely reflecting cerebrovascular vasoconstrictor reserve.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Middle cerebral artery velocity (MCA\n v<\/jats:sub>\n ) increases progressively during incremental running, contrasting with the inverted\u2010U response observed during cycling.\n <\/jats:p>\n <\/jats:list-item>\n \n \n We investigated whether this divergent response was explained by foot strike\u2010induced pulsatility oscillations or altered cerebrovascular CO\n 2<\/jats:sub>\n reactivity (CVR).\n <\/jats:p>\n <\/jats:list-item>\n \n \n Removing pulsatility oscillations, by synchronizing foot\u2010strike with the cardiac cycle, had no effect on the MCA\n v<\/jats:sub>\n mean, indicating that pulsatility oscillations do not explain the continued increase in MCA\n v<\/jats:sub>\n during running.\n <\/jats:p>\n <\/jats:list-item>\n \n In contrast, hypocapnic CVR was markedly attenuated during high\u2010intensity running. Follow\u2010up experiments demonstrated that hypocapnic vasoconstrictor reserve progressively declined with increasing exercise intensity and was related to the increase in mean arterial pressure (MAP) but was similar during running and cycling when MAP was matched.<\/jats:p>\n <\/jats:list-item>\n \n \n These findings show that the progressive increase in MCA\n v<\/jats:sub>\n during running is facilitated by a reduced responsiveness to hypocapnia, which appears related to the prevailing arterial pressure rather than modality\n per se<\/jats:italic>\n . This attenuation likely reflects a reduced cerebrovascular vasoconstrictor reserve.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp288117","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:00:25Z","timestamp":1788328825000},"page":"8501-8522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms regulating cerebral perfusion during running exercise: Influence of foot strike\u2010induced pulsatility oscillations, CO\n 2<\/sub>\n reactivity and BP"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0357-6561","authenticated-orcid":false,"given":"Lydia L.","family":"Simpson","sequence":"first","affiliation":[{"name":"Department of Sport Science Universit\u00e4t Innsbruck Innsbruck Austria"},{"name":"Bristol Medical School, Translational Health Sciences University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-8508","authenticated-orcid":false,"given":"Dean R.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Sport Science Universit\u00e4t Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor A.","family":"Howe","sequence":"additional","affiliation":[{"name":"Department of Sport Science Universit\u00e4t Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-8430","authenticated-orcid":false,"given":"Christina D.","family":"Bruce","sequence":"additional","affiliation":[{"name":"Department of Sport Science Universit\u00e4t Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William K.","family":"Cornwell","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2010Cardiology University of Colorado Anschutz Medical Campus Aurora Colorado USA"},{"name":"Clinical Translational Research Center University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2166-7966","authenticated-orcid":false,"given":"Justin S.","family":"Lawley","sequence":"additional","affiliation":[{"name":"Department of Sport Science Universit\u00e4t Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00854.2014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00062.2003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2014.08.013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00285.2014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-200207000-00024"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.12273"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14539"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199305000-00006"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.066969"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277321"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.28.5.449"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.4.1.65"},{"key":"e_1_2_7_14_1","first-page":"954","article-title":"Difference between end\u2010tidal and arterial PCO2${{{\\mathrm{P}}}_{{\\mathrm{C}}{{{\\mathrm{O}}}_2}}}$ in exercise","volume":"47","author":"Jones N. 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