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Trans. R. Soc. B"],"published-print":{"date-parts":[[2021,1,4]]},"abstract":"<jats:p>\n                    Several current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain and\n                    <jats:italic>decreases<\/jats:italic>\n                    when oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O\n                    <jats:sub>2<\/jats:sub>\n                    \/CO\n                    <jats:sub>2<\/jats:sub>\n                    ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not owing to feedback from a hypothetical O\n                    <jats:sub>2<\/jats:sub>\n                    sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O\n                    <jats:sub>2<\/jats:sub>\n                    and CO\n                    <jats:sub>2<\/jats:sub>\n                    transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.\n                  <\/jats:p>\n                  <jats:p>This article is part of the theme issue \u2018Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2019.0624","type":"journal-article","created":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T19:05:22Z","timestamp":1605467122000},"page":"20190624","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow"],"prefix":"10.1098","volume":"376","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-1256","authenticated-orcid":true,"given":"Richard B.","family":"Buxton","sequence":"first","affiliation":[{"name":"Department of Radiology, University of California San Diego, 9500 Gilman Drive, MC 0677, La Jolla, CA 92093-0677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-543-5_1"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200110000-00001"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(02)02264-6"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.35"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17708691"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00135-0"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214912110"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112819"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.231"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.01.032"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(00)00038-2"},{"key":"e_1_3_5_13_2","volume-title":"Brain energy metabolism","author":"Siesjo B","year":"1978"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00062.2017"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3260686"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02803-7"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.12.010"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0026-12.2012"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909711107"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.4.1140"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0916"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.05.038"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.01.036"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600030"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21171"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-0056-2_22"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1834"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9403"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.11.050"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.10.049"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200105000-00005"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.11.015"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.01.038"},{"key":"e_1_3_5_34_2","first-page":"H554","article-title":"Effect of stepped hypoglycemia on regional cerebral blood flow response to physiological brain activation","volume":"270","author":"Powers WJ","year":"1996","journal-title":"Am. 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