{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:42:06Z","timestamp":1787316126235,"version":"build-2736575974"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec id=\"ab-ybr260001-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform efforts to develop more targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether the neurophysiologic signatures of ketamine are associated with removal of conscious awareness using general anesthesia (GA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This cohort study was a secondary analysis of participant-level data from 3 prospective studies conducted between 2017 and 2023. The primary analysis included data from 2 study cohorts (University of Michigan and Stanford University), and the supplementary analysis included data from a third cohort (University of Auckland). The study cohorts included healthy volunteers, patients undergoing elective surgery, and patients with a diagnosis of depression (all aged \u226518 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-7\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>Participants received a subanesthetic infusion of ketamine (0.5 mg\/kg body weight) over 40 minutes or placebo with or without GA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was change in electroencephalographic (EEG) band power during medication infusion. Changes were computed using nonparametric paired statistical text (Wilcoxon signed-rank test).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This study included 52 participants in the primary analysis (mean [SD] age, 43.4 [18.3] years; 34 females [65.4%]) and 27 additional participants in the supplementary analysis (mean [SD] age, 30.2 [8.2] years; 15 females [55.6%]). GA differentially altered EEG features commonly associated with ketamine in all 52 participants (100%) in the primary analysis. Compared with awake administration, ketamine administered during GA preserved its \u03b2\u03b3 power modulation (mean [SEM] increase from 6.3 [11.3] to 11.6 [2.2] dB for awake administration; increase from 8.5 [2.9] to 11.2 [3.8] dB for administration during GA) but lacked its characteristic \u03b8 augmentation (increase from 17.3 [10.5] to 22.9 [3.1] dB during awake administration; nonsignificant decrease from 29.0 [3.0] to 27.8 [3.5] dB for administration during GA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ybr260001-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this cohort study, coadministration of ketamine with GA selectively modulated the \u03b8 but not the \u03b2\u03b3 neurophysiologic correlates of ketamine. These findings suggest a potential method to explore the role of these components in the behavioral effects of ketamine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2026.0190","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:00:16Z","timestamp":1775660416000},"page":"640","source":"Crossref","is-referenced-by-count":3,"title":["General Anesthesia and Discrete Components of Ketamine Neurophysiology"],"prefix":"10.1001","volume":"83","author":[{"given":"Ben","family":"Deverett","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa R.","family":"Lii","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip E.","family":"Vlisides","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Tarnal","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Forsyth","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Sumner","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilleriin","family":"Sikka","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California"},{"name":"Department of Psychology, Stanford University, Stanford, California"},{"name":"Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Sk\u00f6vde, Sk\u00f6vde, Sweden"},{"name":"Department of Psychology, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan F.","family":"Schatzberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Muthukumaraswamy","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Mashour","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Center for Consciousness Science, University of Michigan Medical School, Ann Arbor"},{"name":"Neuroscience Graduate Program, Department of Pharmacology, University of Michigan Medical School, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris D.","family":"Heifets","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California"},{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"ybr260001r1","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3389\/fnhum.2016.00612","article-title":"Ketamine: 50 years of modulating the mind.","volume":"10","author":"Li","year":"2016","journal-title":"Front Hum Neurosci"},{"issue":"6","key":"ybr260001r2","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1016\/j.clinph.2016.03.005","article-title":"Electroencephalogram signatures of ketamine anesthesia-induced unconsciousness.","volume":"127","author":"Akeju","year":"2016","journal-title":"Clin Neurophysiol"},{"issue":"1","key":"ybr260001r3","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1097\/ALN.0000000000001671","article-title":"Neurophysiologic correlates of ketamine sedation and anesthesia: a high-density electroencephalography study in healthy volunteers.","volume":"127","author":"Vlisides","year":"2017","journal-title":"Anesthesiology"},{"issue":"1","key":"ybr260001r4","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1038\/s41467-023-37463-3","article-title":"Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology.","volume":"14","author":"Tian","year":"2023","journal-title":"Nat Commun"},{"issue":"33","key":"ybr260001r5","doi-asserted-by":"publisher","first-page":"11694","DOI":"10.1523\/JNEUROSCI.0903-15.2015","article-title":"Evidence that subanesthetic doses of ketamine cause sustained disruptions of NMDA and AMPA-mediated frontoparietal connectivity in humans.","volume":"35","author":"Muthukumaraswamy","year":"2015","journal-title":"J Neurosci"},{"issue":"22","key":"ybr260001r6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2402732121","article-title":"Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.","volume":"121","author":"Adam","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7827","key":"ybr260001r7","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41586-020-2731-9","article-title":"Deep posteromedial cortical rhythm in dissociation.","volume":"586","author":"Vesuna","year":"2020","journal-title":"Nature"},{"issue":"8","key":"ybr260001r8","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J Neurosci"},{"issue":"3","key":"ybr260001r9","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1097\/ALN.0000000000001512","article-title":"Paradoxical emergence: administration of subanesthetic ketamine during isoflurane anesthesia induces burst suppression but accelerates recovery.","volume":"126","author":"Hambrecht-Wiedbusch","year":"2017","journal-title":"Anesthesiology"},{"key":"ybr260001r10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.neuroimage.2019.03.076","article-title":"Cortical dynamics during psychedelic and anesthetized states induced by ketamine.","volume":"196","author":"Li","year":"2019","journal-title":"Neuroimage"},{"issue":"11","key":"ybr260001r11","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/s44220-023-00140-x","article-title":"Randomized trial of ketamine masked by surgical anesthesia in patients with depression.","volume":"1","author":"Lii","year":"2023","journal-title":"Nat Ment Health"},{"key":"ybr260001r12","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2019.109838","article-title":"Simultaneous EEG\/fMRI recorded during ketamine infusion in patients with major depressive disorder.","volume":"99","author":"McMillan","year":"2020","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"issue":"1","key":"ybr260001r13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.bpsc.2019.07.002","article-title":"Ketamine enhances visual sensory evoked potential long-term potentiation in patients with major depressive disorder.","volume":"5","author":"Sumner","year":"2020","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"6","key":"ybr260001r14","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1038\/s41380-023-01945-z","article-title":"Efficacy and safety of perioperative application of ketamine on postoperative depression: a meta-analysis of randomized controlled studies.","volume":"28","author":"Guo","year":"2023","journal-title":"Mol Psychiatry"},{"issue":"5","key":"ybr260001r15","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.bja.2018.03.030","article-title":"Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.","volume":"121","author":"Mashour","year":"2018","journal-title":"Br J Anaesth"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2847665\/jamapsychiatry_deverett_2026_br_260001_1779900185.02967.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:00:28Z","timestamp":1780498828000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2847665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2026.0190","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}