{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:48:28Z","timestamp":1792219708963,"version":"4.4.0"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council"},{"name":"Medical Research Council","award":["MC_UP_1201\/4"],"award-info":[{"award-number":["MC_UP_1201\/4"]}]},{"name":"Medical Research Council","award":["602150"],"award-info":[{"award-number":["602150"]}]},{"name":"European Union\u2019s 7th Framework","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"DOI":"10.13039\/501100007731","name":"Hannelore Kohl Stiftung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018727","name":"One Mind","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018727","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Integra LifeSciences Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Patients undergo interventions to achieve a \u2018normal\u2019 brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults.<\/jats:p>\n               <jats:p>We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements and without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20\u201340 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day.<\/jats:p>\n               <jats:p>In patients (n\u2009=\u2009114), brain temperature ranged from 32.6 to 42.3\u00b0C and mean brain temperature (38.5\u2009\u00b1\u20090.8\u00b0C) exceeded body temperature (37.5\u2009\u00b1\u20090.5\u00b0C, P\u2009&amp;lt;\u20090.0001). Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P\u2009=\u20090.018). In healthy participants, brain temperature ranged from 36.1 to 40.9\u00b0C; mean brain temperature (38.5\u2009\u00b1\u20090.4\u00b0C) exceeded oral temperature (36.0\u2009\u00b1\u20090.5\u00b0C) and was 0.36\u00b0C higher in luteal females relative to follicular females and males (P\u2009=\u20090.0006 and P\u2009&amp;lt;\u20090.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6\u00b0C over 20 years, P\u2009=\u20090.0002), and varied spatially by 2.41\u2009\u00b1\u20090.46\u00b0C with highest temperatures in the thalamus. Brain temperature varied by time of day, especially in deep regions (0.86\u00b0C, P\u2009=\u20090.0001), and was lowest at night. From the healthy data we built HEATWAVE\u2014a 4D map of human brain temperature. Testing the clinical relevance of HEATWAVE in patients, we found that lack of a daily brain temperature rhythm increased the odds of death in intensive care 21-fold (P\u2009=\u20090.016), whilst absolute temperature maxima or minima did not predict outcome. A warmer mean brain temperature was associated with survival (P\u2009=\u20090.035), however, and ageing by 10 years increased the odds of death 11-fold (P\u2009=\u20090.0002).<\/jats:p>\n               <jats:p>Human brain temperature is higher and varies more than previously assumed\u2014by age, sex, menstrual cycle, brain region, and time of day. This has major implications for temperature monitoring and management, with daily brain temperature rhythmicity emerging as one of the strongest single predictors of survival after brain injury. We conclude that daily rhythmic brain temperature variation\u2014not absolute brain temperature\u2014is one way in which human brain physiology may be distinguished from pathophysiology.<\/jats:p>","DOI":"10.1093\/brain\/awab466","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T20:12:31Z","timestamp":1639685551000},"page":"2031-2048","source":"Crossref","is-referenced-by-count":125,"title":["A daily temperature rhythm in the human brain predicts survival after brain injury"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-5019","authenticated-orcid":false,"given":"Nina M","family":"Rzechorzek","sequence":"first","affiliation":[{"name":"MRC Laboratory of Molecular Biology , Cambridge CB2 0QH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-9917","authenticated-orcid":false,"given":"Michael 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8350-8093","authenticated-orcid":false,"given":"Ari","family":"Ercole","sequence":"additional","affiliation":[{"name":"Division of Anaesthesia, University of Cambridge, Box 93 Addenbrooke\u2019s Hospital , Cambridge CB2 0QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-6544","authenticated-orcid":false,"given":"Manuel","family":"Cabeleira","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Box 167, Cambridge Biomedical Campus, Addenbrooke\u2019s Hospital , Cambridge CB2 0QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The CENTER-TBI High Resolution ICU (HR ICU) Sub-Study Participants and Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-4579","authenticated-orcid":false,"given":"Jonathan","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Critical Care and Pain Medicine, NHS Lothian , Room No. S8208 (2nd Floor), Royal Infirmary of Edinburgh, Edinburgh EH16 4SA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4445-1551","authenticated-orcid":false,"given":"Ian","family":"Marshall","sequence":"additional","affiliation":[{"name":"Edinburgh Imaging (Royal Infirmary of Edinburgh) Facility , Edinburgh EH16 4SA , UK"},{"name":"Centre for Clinical Brain Sciences, University of Edinburgh , Edinburgh EH16 4SB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-6096","authenticated-orcid":false,"given":"John 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