{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:00:17Z","timestamp":1792414817260,"version":"4.4.0"},"reference-count":79,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS129836"],"award-info":[{"award-number":["R01NS129836"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:p>While current arousal level assessments in patients with disorders of consciousness discriminate altered states of consciousness, there are significant limitations in characterizing the transition from one state to another or quantifying the frequent arousal level fluctuations observed in a patient. Here, we identified a repeated, temporally discrete, dynamical pattern evident in the recovery of consciousness from anesthesia and brain injury coma models in rodents. We prospectively validated these features we label \u201cArousal Units\u201d (AU) in neonatal humans recovering from static hypoxic injuries and senior patients emerging from anesthesia indicating their generalizability. The AUs lawfully link changes in spectral power and breathing frequency and reliably associate with motor changes. Distinctive cortical patterns within AUs can be transformed into arousal indices, determining arousal levels. The reliability of these events is demonstrated across intact and brain-injured states and translates to the human brain; extracting these stereotyped dynamics could aid anesthesia monitoring, tracking coma recovery, and identifying cognitive motor dissociation.<\/jats:p>","DOI":"10.1073\/pnas.2413789122","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T15:08:54Z","timestamp":1746457734000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Cortical signatures linked to behavior quantitatively track arousal levels"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-6320","authenticated-orcid":false,"given":"Sijia","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-2805","authenticated-orcid":false,"given":"Yelena","family":"Bibineyshvili","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3598-368X","authenticated-orcid":false,"given":"Seyed A.","family":"Safavynia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-3406","authenticated-orcid":false,"given":"Juan","family":"Calder\u00f3n-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-0932","authenticated-orcid":false,"given":"Zachary M.","family":"Grinspan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9900-7146","authenticated-orcid":false,"given":"Diany P.","family":"Calderon","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Weill Cornell Medical College","place":["New York"]},{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medical College","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207067"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002559"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-020-01133-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26342"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/LRA.S230728"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0963180121000086"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6429"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-021-01289-y"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2018.07.002"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2018.07.001"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-310958"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-015-0455-5"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10797-7"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.05.025"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77162-3"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049933"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-0102(94)90038-8"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.05.005"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.10.078"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00342722"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1980.43.1.118"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3687"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2006.07.011"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"M. A. Prucnal A. G. Polak \u201cEffectiveness of sleep apnea detection based on one vs. two symmetrical EEG channels\u201d in 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (IEEE Piscataway NJ 2019) pp. 4056\u20134059.","DOI":"10.1109\/EMBC.2019.8856632"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2008.02.032"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2021.787157"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aes265"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5259.271"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2023.105262"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310025111"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00641.2002"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.07886","article-title":"Phase-amplitude coupling supports phase coding in human ECoG","volume":"4","author":"Watrous A. J.","year":"2015","unstructured":"A. J. Watrous, L. Deuker, J. Fell, N. Axmacher, Phase-amplitude coupling supports phase coding in human ECoG. Elife 4, e07886 (2015).","journal-title":"Elife"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2126-13.2013"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67355"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147275"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1040975"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1119-4"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac335"},{"key":"e_1_3_4_39_2","volume-title":"Neonatal Behavioral Assessment Scale","author":"Brazelton T. B.","year":"1995","unstructured":"T. B. Brazelton, J. K. Nugent, Neonatal Behavioral Assessment Scale (Cambridge University Press, 1995)."},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pjnns.2013.09.001"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1982.tb08643.x"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb00306.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254053"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.2741\/1074"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0444-2"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10877-016-9911-z"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00607.2010"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28451-0"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-022-01335-5"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089576"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(86)90011-1"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.10.023"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2022.108316"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28090-5"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/anae.14609"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(22)00196-0"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac340"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.concog.2017.05.002"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.01.024"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55092"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-023-03167-w"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38972-x"},{"key":"e_1_3_4_63_2","first-page":"25","article-title":"Automated EEG entropy measurements in coma, vegetative state\/unresponsive wakefulness syndrome and minimally conscious state","volume":"26","author":"Gosseries O.","year":"2011","unstructured":"O. Gosseries , Automated EEG entropy measurements in coma, vegetative state\/unresponsive wakefulness syndrome and minimally conscious state. Funct. Neurol. 26, 25\u201330 (2011).","journal-title":"Funct. Neurol."},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006294"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10120917"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2014.06.018"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10125-w"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2370-4"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/09602011.2016.1214604"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00138"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2021.109217"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.03.029"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2020.00050"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6329"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3181c07428"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00428-x"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0637"},{"key":"e_1_3_4_78_2","unstructured":"S. Gao Cortical signatures linked to behavior quantitatively track arousal levels. Dryad. https:\/\/datadryad.org\/dataset\/doi:10.5061\/dryad.v15dv4246. Deposited 1 April 2024."},{"key":"e_1_3_4_79_2","unstructured":"S. Gao Arousal_units. GitHub. https:\/\/github.com\/Calderonlab\/arousal_units. Deposited 1 April 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2413789122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T15:09:48Z","timestamp":1746457788000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2413789122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":79,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,5,13]]}},"alternative-id":["10.1073\/pnas.2413789122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2413789122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]},"assertion":[{"value":"2024-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2413789122"}}