Recovery of consciousness and cognition after general anesthesia in humans

George A Mashour, Ben JA Palanca, Mathias Basner, Duan Li, Wei Wang, Stefanie Blain-Moraes, Nan Lin, Kaitlyn Maier, Maxwell Muench, Vijay Tarnal, Giancarlo Vanini, E Andrew Ochroch, Rosemary Hogg, Marlon Schwartz, Hannah Maybrier, Randall Hardie, Ellen Janke, Goodarz Golmirzaie, Paul Picton, Andrew R McKinstry-Wu, Michael S Avidan, Max B Kelz, George A Mashour, Ben JA Palanca, Mathias Basner, Duan Li, Wei Wang, Stefanie Blain-Moraes, Nan Lin, Kaitlyn Maier, Maxwell Muench, Vijay Tarnal, Giancarlo Vanini, E Andrew Ochroch, Rosemary Hogg, Marlon Schwartz, Hannah Maybrier, Randall Hardie, Ellen Janke, Goodarz Golmirzaie, Paul Picton, Andrew R McKinstry-Wu, Michael S Avidan, Max B Kelz

Abstract

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory.

Trial registration: ClinicalTrials.gov NCT01911195.

Keywords: anesthesia; cognition; consciousness; frontal cortex; human; medicine; neuroscience.

Conflict of interest statement

GM, BP, MB, DL, WW, SB, NL, KM, MM, VT, GV, EO, RH, MS, HM, RH, EJ, GG, PP, AM, MA, MK No competing interests declared

© 2021, Mashour et al.

Figures

Figure 1.. Experimental design.
Figure 1.. Experimental design.
Participants were randomized to one of two groups for investigating recovery of consciousness and cognition after general anesthesia. Sleep-wake actigraphy data were acquired in the week leading up to the day of the experiment, which started with baseline cognitive testing followed by either a period of general anesthesia (1.3 age-adjusted minimum alveolar concentration of isoflurane) or wakefulness. Upon recovery of consciousness (or similar time point for controls), recurrent cognitive testing was performed for 3 hr. Actigraphy resumed for 3 days after the experiment.
Figure 2.. Time course for recovery of…
Figure 2.. Time course for recovery of (normalized) accuracy in cognitive task performance after general anesthesia (time 0 is just after recovery of consciousness in the group that was anesthetized).
AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test. The six cognitive tests are all represented.
Figure 3.. Time course for recovery of…
Figure 3.. Time course for recovery of (normalized) speed of cognitive task performance after general anesthesia (time 0 is just after recovery of consciousness in the group that was anesthetized).
AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test. The six cognitive tests are all represented.
Figure 4.. Cortical dynamics before, during, and…
Figure 4.. Cortical dynamics before, during, and after general anesthesia.
(A) Scalp topographic maps of the group-level permutation entropy (PE; median average across N = 30 participants) at the ten studied epochs. (B) The box plots of average PE values in frontal (Fp1, Fp2, Fpz, F3, F4, and Fz) and posterior channels (P3, P4, Pz, O1, O2, and Oz) for the studied epochs. On each box, the central mark is the median, the edges are the 25th and 75th percentiles, the whiskers extend to the most extreme data points determined by the MATLAB algorithm to be non-outliers, and the points deemed by the algorithm to be outliers are plotted individually (red cross). (C) The box plots of LZC values for the studied epochs. EC = eyes closed resting state (EC1 is baseline consciousness, EC2-7 are post-emergence just prior to cognitive testing), LOC = loss of consciousness, Pre-ROC = 2 min epoch just before recovery of consciousness. *indicates significant difference relative to EC1, using linear mixed model analysis (Bonferroni-corrected p<0.05).
Figure 4—figure supplement 1.. Confirmatory results of…
Figure 4—figure supplement 1.. Confirmatory results of permutation entropy (PE) with different settings of embedding dimension (dE) and time delay (τ).
The description of the figure and statistical results are the same as those in Figure 4A-B.
Figure 4—figure supplement 2.. Confirmatory results of…
Figure 4—figure supplement 2.. Confirmatory results of Lempel-Ziv Complexity (LZC).
(A) Sensitivity of the LZC measure to the selection of threshold for binarization. (B) Confirmatory results of LZC by using spatial shuffling (top) and phase randomization (bottom) in the generation of surrogate data for normalization. The spatial shuffling method permutates the spatial order (at each time point) of the spatiotemporal matrix. The phase randomization method preserves the spectral profile of the signals and reflects the complexity changes beyond the power spectrogram. The description of the figure and the statistical results are same with those in Figure 4C.
Figure 4—figure supplement 3.. Cortical dynamics as…
Figure 4—figure supplement 3.. Cortical dynamics as assessed by permutation (PE) and Lempel-Ziv complexity (LZC) for the non-anesthetized control group.
(A) Scalp topographic maps of the group-level PE at the seven resting-state eyes-closed (EC) epochs. (B) The box plots of average PE values in frontal and posterior channels for the studied epochs. (C) The box plots of LZC values for the studied epochs.
Figure 4—figure supplement 4.. Associations between EEG…
Figure 4—figure supplement 4.. Associations between EEG measures during pre-anesthetic baseline (EC1) with the impairment of cognitive functions at emergence (just after recovery of consciousness).
The EEG measures do not appear to be related to the degree of performance impairment via Spearman’s rank correlation analysis. AM, Abstract Matching; DSST, Digit Symbol Substitution Test; MP, Motor Praxis; NBCK, Fractal 2-Back; PVT, Psychomotor Vigilance Test; VOLT, Visual Object Learning Test; RT, Response time; ACC, Accuracy.
Figure 4—figure supplement 5.. Associations between EEG…
Figure 4—figure supplement 5.. Associations between EEG measures during maintenance with the impairment of cognitive functions at emergence.
Only significant correlations were indicated (Spearman’s rank correlation, p

Figure 4—figure supplement 6.. Associations between EEG…

Figure 4—figure supplement 6.. Associations between EEG measures during pre-ROC with the impairment of cognitive…

Figure 4—figure supplement 6.. Associations between EEG measures during pre-ROC with the impairment of cognitive functions at emergence.
Only significant correlations are indicated (Spearman’s rank correlation, p

Figure 5.. Effects of anesthetic exposure on…

Figure 5.. Effects of anesthetic exposure on rest-activity rhythms.

( A ) Rest activity plots…

Figure 5.. Effects of anesthetic exposure on rest-activity rhythms.
(A) Rest activity plots are displayed in the week prior to the study day for volunteers that were subsequently randomized to anesthetized (purple) or control (black) conditions. (B) Rest-activity rhythms in the same participants are displayed on the evening of the study day and for the ensuing days. Time = 0 corresponds to midnight on the evening of the study day.

Figure 6.. Summary of the study findings.

Figure 6.. Summary of the study findings.

Figure 6.. Summary of the study findings.

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    1. Abásolo D, Simons S, Morgado da Silva R, Tononi G, Vyazovskiy VV. Lempel-Ziv complexity of cortical activity during sleep and waking in rats. Journal of Neurophysiology. 2015;113:2742–2752. doi: 10.1152/jn.00575.2014. - DOI - PMC - PubMed
    1. Avidan MS, Evers AS. The Fallacy of Persistent Postoperative Cognitive Decline. Anesthesiology. 2016;124:255–258. doi: 10.1097/ALN.0000000000000958. - DOI - PMC - PubMed
    1. Bandt C, Pompe B. Permutation entropy: a natural complexity measure for time series. Physical Review Letters. 2002;88:174102. doi: 10.1103/PhysRevLett.88.174102. - DOI - PubMed
    1. Banks MI, Krause BM, Endemann CM, Campbell DI, Kovach CK, Dyken ME, Kawasaki H, Nourski KV. Cortical functional connectivity indexes arousal state during sleep and anesthesia. NeuroImage. 2020;211:116627. doi: 10.1016/j.neuroimage.2020.116627. - DOI - PMC - PubMed
    1. Basner M, Mollicone D, Dinges DF. Validity and Sensitivity of a Brief Psychomotor Vigilance Test (PVT-B) to Total and Partial Sleep Deprivation. Acta Astronautica. 2011;69:949–959. doi: 10.1016/j.actaastro.2011.07.015. - DOI - PMC - PubMed
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Figure 4—figure supplement 6.. Associations between EEG…
Figure 4—figure supplement 6.. Associations between EEG measures during pre-ROC with the impairment of cognitive functions at emergence.
Only significant correlations are indicated (Spearman’s rank correlation, p

Figure 5.. Effects of anesthetic exposure on…

Figure 5.. Effects of anesthetic exposure on rest-activity rhythms.

( A ) Rest activity plots…

Figure 5.. Effects of anesthetic exposure on rest-activity rhythms.
(A) Rest activity plots are displayed in the week prior to the study day for volunteers that were subsequently randomized to anesthetized (purple) or control (black) conditions. (B) Rest-activity rhythms in the same participants are displayed on the evening of the study day and for the ensuing days. Time = 0 corresponds to midnight on the evening of the study day.

Figure 6.. Summary of the study findings.

Figure 6.. Summary of the study findings.

Figure 6.. Summary of the study findings.

Author response image 1.

Author response image 1.

Author response image 1.

Author response image 2.

Author response image 2.

Author response image 2.
All figures (14)
Figure 5.. Effects of anesthetic exposure on…
Figure 5.. Effects of anesthetic exposure on rest-activity rhythms.
(A) Rest activity plots are displayed in the week prior to the study day for volunteers that were subsequently randomized to anesthetized (purple) or control (black) conditions. (B) Rest-activity rhythms in the same participants are displayed on the evening of the study day and for the ensuing days. Time = 0 corresponds to midnight on the evening of the study day.
Figure 6.. Summary of the study findings.
Figure 6.. Summary of the study findings.
Author response image 1.
Author response image 1.
Author response image 2.
Author response image 2.

References

    1. Abásolo D, Simons S, Morgado da Silva R, Tononi G, Vyazovskiy VV. Lempel-Ziv complexity of cortical activity during sleep and waking in rats. Journal of Neurophysiology. 2015;113:2742–2752. doi: 10.1152/jn.00575.2014.
    1. Avidan MS, Evers AS. The Fallacy of Persistent Postoperative Cognitive Decline. Anesthesiology. 2016;124:255–258. doi: 10.1097/ALN.0000000000000958.
    1. Bandt C, Pompe B. Permutation entropy: a natural complexity measure for time series. Physical Review Letters. 2002;88:174102. doi: 10.1103/PhysRevLett.88.174102.
    1. Banks MI, Krause BM, Endemann CM, Campbell DI, Kovach CK, Dyken ME, Kawasaki H, Nourski KV. Cortical functional connectivity indexes arousal state during sleep and anesthesia. NeuroImage. 2020;211:116627. doi: 10.1016/j.neuroimage.2020.116627.
    1. Basner M, Mollicone D, Dinges DF. Validity and Sensitivity of a Brief Psychomotor Vigilance Test (PVT-B) to Total and Partial Sleep Deprivation. Acta Astronautica. 2011;69:949–959. doi: 10.1016/j.actaastro.2011.07.015.
    1. Basner M, Savitt A, Moore TM, Port AM, McGuire S, Ecker AJ, Nasrini J, Mollicone DJ, Mott CM, McCann T, Dinges DF, Gur RC. Development and validation of the cognition test battery for spaceflight. Aerospace Medicine and Human Performance. 2015;86:942–952. doi: 10.3357/AMHP.4343.2015.
    1. Basner M, Hermosillo E, Nasrini J, McGuire S, Saxena S, Moore TM, Gur RC, Dinges DF. Repeated administration effects on psychomotor vigilance test performance. Sleep. 2018;41:zsx187. doi: 10.1093/sleep/zsx187.
    1. Berman KF, Ostrem JL, Randolph C, Gold J, Goldberg TE, Coppola R, Carson RE, Herscovitch P, Weinberger DR. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study. Neuropsychologia. 1995;33:1027–1046. doi: 10.1016/0028-3932(95)00035-2.
    1. Blain-Moraes S, Tarnal V, Vanini G, Bel-Behar T, Janke E, Picton P, Golmirzaie G, Palanca BJA, Avidan MS, Kelz MB, Mashour GA. Network efficiency and posterior alpha patterns are markers of recovery from general anesthesia: a High-Density electroencephalography study in healthy volunteers. Frontiers in Human Neuroscience. 2017;11:328. doi: 10.3389/fnhum.2017.00328.
    1. Block N. Two neural correlates of consciousness. Trends in Cognitive Sciences. 2005;9:46–52. doi: 10.1016/j.tics.2004.12.006.
    1. Callaway JK, Jones NC, Royse CF. Isoflurane induces cognitive deficits in the morris water maze task in rats. European Journal of Anaesthesiology. 2012;29:239–245. doi: 10.1097/EJA.0b013e32835103c1.
    1. Carr ZJ, Torjman MC, Manu K, Dy G, Goldberg ME. Spatial memory using active allothetic place avoidance in adult rats after isoflurane anesthesia: a potential model for postoperative cognitive dysfunction. Journal of Neurosurgical Anesthesiology. 2011;23:138–145. doi: 10.1097/ANA.0b013e3182049f19.
    1. Casali AG, Gosseries O, Rosanova M, Boly M, Sarasso S, Casali KR, Casarotto S, Bruno M-A, Laureys S, Tononi G, Massimini M. A theoretically based index of consciousness independent of sensory processing and behavior. Science Translational Medicine. 2013;5:198ra105. doi: 10.1126/scitranslmed.3006294.
    1. Chennu S, O'Connor S, Adapa R, Menon DK, Bekinschtein TA. Brain connectivity dissociates responsiveness from drug exposure during Propofol-Induced transitions of consciousness. PLOS Computational Biology. 2016;12:e1004669. doi: 10.1371/journal.pcbi.1004669.
    1. Cole RJ, Kripke DF, Gruen W, Mullaney DJ, Gillin JC. Automatic sleep/wake identification from wrist activity. Sleep. 1992;15:461–469. doi: 10.1093/sleep/15.5.461.
    1. Culley DJ, Baxter MG, Yukhananov R, Crosby G. Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats. Anesthesiology. 2004;100:309–314. doi: 10.1097/00000542-200402000-00020.
    1. Dehaene S, Kerszberg M, Changeux JP. A neuronal model of a global workspace in effortful cognitive tasks. PNAS. 1998;95:14529–14534. doi: 10.1073/pnas.95.24.14529.
    1. Dehaene S, Changeux JP. Experimental and theoretical approaches to conscious processing. Neuron. 2011;70:200–227. doi: 10.1016/j.neuron.2011.03.018.
    1. Delorme A, Makeig S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. Journal of Neuroscience Methods. 2004;134:9–21. doi: 10.1016/j.jneumeth.2003.10.009.
    1. Drummond SP, Bischoff-Grethe A, Dinges DF, Ayalon L, Mednick SC, Meloy MJ. The neural basis of the psychomotor vigilance task. Sleep. 2005;28:1059–1068. doi: 10.1093/sleep/28.9.1059.
    1. Eger EI, Koblin DD, Harris RA, Kendig JJ, Pohorille A, Halsey MJ, Trudell JR. Hypothesis: inhaled anesthetics produce immobility and amnesia by different mechanisms at different sites. Anesthesia and Analgesia. 1997;84:915–918. doi: 10.1097/00000539-199704000-00039.
    1. Eger EI, Gong D, Koblin DD, Bowland T, Ionescu P, Laster MJ, Weiskopf RB. The effect of anesthetic duration on kinetic and recovery characteristics of desflurane versus Sevoflurane, and on the kinetic characteristics of compound A, in volunteers. Anesthesia and Analgesia. 1998;86:414–421. doi: 10.1097/00000539-199802000-00037.
    1. Franco L, Sánchez C, Bravo R, Rodríguez AB, Barriga C, Romero E, Cubero J. The sedative effect of non-alcoholic beer in healthy female nurses. PLOS ONE. 2012;7:e37290. doi: 10.1371/journal.pone.0037290.
    1. Geng Y, Wu Q, Zhang R. Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: a randomized controlled trial. Journal of Clinical Anesthesia. 2017;38:165–171. doi: 10.1016/j.jclinane.2017.02.007.
    1. Geoghegan P, O'Donovan MT, Lawlor BA. Investigation of the effects of alcohol on sleep using actigraphy. Alcohol and Alcoholism. 2012;47:538–544. doi: 10.1093/alcalc/ags054.
    1. Glahn DC, Gur RC, Ragland JD, Censits DM, Gur RE. Reliability, performance characteristics, construct validity, and an initial clinical application of a visual object learning test (VOLT) Neuropsychology. 1997;11:602–612. doi: 10.1037//0894-4105.11.4.602.
    1. Glahn DC, Cannon TD, Gur RE, Ragland JD, Gur RC. Working memory constrains abstraction in schizophrenia. Biological Psychiatry. 2000;47:34–42. doi: 10.1016/S0006-3223(99)00187-0.
    1. Gur RC, Ragland JD, Moberg PJ, Turner TH, Bilker WB, Kohler C, Siegel SJ, Gur RE. Computerized neurocognitive scanning: I. methodology and validation in healthy people. Neuropsychopharmacology. 2001;25:766–776. doi: 10.1016/S0893-133X(01)00278-0.
    1. Gur RC, Richard J, Hughett P, Calkins ME, Macy L, Bilker WB, Brensinger C, Gur RE. A cognitive neuroscience-based computerized battery for efficient measurement of individual differences: standardization and initial construct validation. Journal of Neuroscience Methods. 2010;187:254–262. doi: 10.1016/j.jneumeth.2009.11.017.
    1. Hemmings HC, Riegelhaupt PM, Kelz MB, Solt K, Eckenhoff RG, Orser BA, Goldstein PA. Towards a comprehensive understanding of anesthetic mechanisms of action: a decade of discovery. Trends in Pharmacological Sciences. 2019;40:464–481. doi: 10.1016/j.tips.2019.05.001.
    1. Hudetz AG, Liu X, Pillay S, Boly M, Tononi G. Propofol anesthesia reduces Lempel-Ziv complexity of spontaneous brain activity in rats. Neuroscience Letters. 2016;628:132–135. doi: 10.1016/j.neulet.2016.06.017.
    1. Jackson O, Schacter DL. Encoding activity in anterior medial temporal lobe supports subsequent associative recognition. NeuroImage. 2004;21:456–462. doi: 10.1016/j.neuroimage.2003.09.050.
    1. Jasper I, Häussler A, Marquardt C, Hermsdörfer J. Circadian rhythm in handwriting. Journal of Sleep Research. 2009;18:264–271. doi: 10.1111/j.1365-2869.2008.00727.x.
    1. Jevtovic-Todorovic V, Absalom AR, Blomgren K, Brambrink A, Crosby G, Culley DJ, Fiskum G, Giffard RG, Herold KF, Loepke AW, Ma D, Orser BA, Planel E, Slikker W, Soriano SG, Stratmann G, Vutskits L, Xie Z, Hemmings HC. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA salzburg seminar. British Journal of Anaesthesia. 2013;111:143–151. doi: 10.1093/bja/aet177.
    1. Jiang S, Miao B, Chen Y. Prolonged duration of isoflurane anesthesia impairs spatial recognition memory through the activation of JNK1/2 in the hippocampus of mice. Neuroreport. 2017;28:386–390. doi: 10.1097/WNR.0000000000000760.
    1. Jordan D, Ilg R, Riedl V, Schorer A, Grimberg S, Neufang S, Omerovic A, Berger S, Untergehrer G, Preibisch C, Schulz E, Schuster T, Schröter M, Spoormaker V, Zimmer C, Hemmer B, Wohlschläger A, Kochs EF, Schneider G. Simultaneous electroencephalographic and functional magnetic resonance imaging indicate impaired cortical top-down processing in association with anesthetic-induced unconsciousness. Anesthesiology. 2013;119:1031–1042. doi: 10.1097/ALN.0b013e3182a7ca92.
    1. Kelz MB, García PS, Mashour GA, Solt K. Escape from oblivion: neural mechanisms of emergence from general anesthesia. Anesthesia and Analgesia. 2019;128:726–736. doi: 10.1213/ANE.0000000000004006.
    1. Kelz MB, Mashour GA. The Biology of General Anesthesia from Paramecium to Primate. Current Biology: CB. 2019;29:R1199–R210. doi: 10.1016/j.cub.2019.09.071.
    1. Kim H, Moon JY, Mashour GA, Lee U. Mechanisms of hysteresis in human brain networks during transitions of consciousness and unconsciousness: Theoretical principles and empirical evidence. PLOS Computational Biology. 2018;14:e1006424. doi: 10.1371/journal.pcbi.1006424.
    1. Krause BM, Sabia S, Manning HJ, Singh-Manoux A, Sanders RD. Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study. BMJ. 2019;366:l4466. doi: 10.1136/bmj.l4466.
    1. Långsjö JW, Alkire MT, Kaskinoro K, Hayama H, Maksimow A, Kaisti KK, Aalto S, Aantaa R, Jääskeläinen SK, Revonsuo A, Scheinin H. Returning from oblivion: imaging the neural core of consciousness. Journal of Neuroscience. 2012;32:4935–4943. doi: 10.1523/JNEUROSCI.4962-11.2012.
    1. Lempel A, Ziv J. On the complexity of finite sequences. IEEE Transactions on Information Theory. 1976;22:75–81. doi: 10.1109/TIT.1976.1055501.
    1. Li X, Cui S, Voss LJ. Using permutation entropy to measure the electroencephalographic effects of sevoflurane. Anesthesiology. 2008;109:448–456. doi: 10.1097/ALN.0b013e318182a91b.
    1. Maier KL, McKinstry-Wu AR, Palanca BJA, Tarnal V, Blain-Moraes S, Basner M, Avidan MS, Mashour GA, Kelz MB. Protocol for the reconstructing consciousness and cognition (ReCCognition) Study. Frontiers in Human Neuroscience. 2017;11:284. doi: 10.3389/fnhum.2017.00284.
    1. Mashour GA, Roelfsema P, Changeux JP, Dehaene S. Conscious Processing and the Global Neuronal Workspace Hypothesis. Neuron. 2020;105:776–798. doi: 10.1016/j.neuron.2020.01.026.
    1. Mashour GA, Alkire MT. Evolution of consciousness: phylogeny, ontogeny, and emergence from general anesthesia. PNAS. 2013;110 Suppl 2:10357–10364. doi: 10.1073/pnas.1301188110.
    1. McLeod DR, Griffiths RR, Bigelow GE, Yingling J. An automated version of the digit symbol substitution test (DSST) Behavior Research Methods & Instrumentation. 1982;14:463–466. doi: 10.3758/BF03203313.
    1. Mezick EJ, Matthews KA, Hall M, Kamarck TW, Buysse DJ, Owens JF, Reis SE. Intra-individual variability in sleep duration and fragmentation: associations with stress. Psychoneuroendocrinology. 2009;34:1346–1354. doi: 10.1016/j.psyneuen.2009.04.005.
    1. Neves MC, Albuquerque MR, Neves FS, Lage GM, Malloy-Diniz L, Nicolato R, Corrêa H. Sensorimotor performance in euthymic bipolar disorder: the MPraxis (PennCNP) analysis. Revista Brasileira de Psiquiatria. 2014;36:248–250. doi: 10.1590/1516-4446-2013-1243.
    1. Nickalls RW, Mapleson WW. Age-related iso-MAC charts for isoflurane, sevoflurane and desflurane in man. British Journal of Anaesthesia. 2003;91:170–174. doi: 10.1093/bja/aeg132.
    1. Nir T, Or-Borichev A, Izraitel E, Hendler T, Lerner Y, Matot I. Transient subcortical functional connectivity upon emergence from propofol sedation in human male volunteers: evidence for active emergence. British Journal of Anaesthesia. 2019;123:298–308. doi: 10.1016/j.bja.2019.05.038.
    1. Olofsen E, Sleigh JW, Dahan A. Permutation entropy of the electroencephalogram: a measure of anaesthetic drug effect. British Journal of Anaesthesia. 2008;101:810–821. doi: 10.1093/bja/aen290.
    1. Pal D, Dean JG, Liu T, Li D, Watson CJ, Hudetz AG, Mashour GA. Differential role of prefrontal and parietal cortices in controlling level of consciousness. Current Biology. 2018;28:2145–2152. doi: 10.1016/j.cub.2018.05.025.
    1. Pollard BJ, Bryan A, Bennett D, Faragher EB, Un EN, Keegan M, Wilson A, Burkill M, Beatty PC, Stollery BT. Recovery after oral surgery with halothane, enflurane, isoflurane or propofol anaesthesia. British Journal of Anaesthesia. 1994;72:559–566. doi: 10.1093/bja/72.5.559.
    1. Purdon PL, Pierce ET, Mukamel EA, Prerau MJ, Walsh JL, Wong KF, Salazar-Gomez AF, Harrell PG, Sampson AL, Cimenser A, Ching S, Kopell NJ, Tavares-Stoeckel C, Habeeb K, Merhar R, Brown EN. Electroencephalogram signatures of loss and recovery of consciousness from propofol. PNAS. 2013;110:E1142–E1151. doi: 10.1073/pnas.1221180110.
    1. Raccah O, Block N, Fox KCR, Kcr F. Does the Prefrontal Cortex Play an Essential Role in Consciousness? Insights from Intracranial Electrical Stimulation of the Human Brain. Journal of Neuroscience. 2021;41:2076–2087. doi: 10.1523/JNEUROSCI.1141-20.2020.
    1. Ragland JD, Turetsky BI, Gur RC, Gunning-Dixon F, Turner T, Schroeder L, Chan R, Gur RE. Working memory for complex figures: an fMRI comparison of letter and fractal n-back tasks. Neuropsychology. 2002;16:370–379. doi: 10.1037/0894-4105.16.3.370.
    1. Ranft A, Golkowski D, Kiel T, Riedl V, Kohl P, Rohrer G, Pientka J, Berger S, Thul A, Maurer M, Preibisch C, Zimmer C, Mashour GA, Kochs EF, Jordan D, Ilg R. Neural Correlates of Sevoflurane-induced Unconsciousness Identified by Simultaneous Functional Magnetic Resonance Imaging and Electroencephalography. Anesthesiology. 2016;125:861–872. doi: 10.1097/ALN.0000000000001322.
    1. Reshef ER, Schiff ND, Brown EN. A Neurologic Examination for Anesthesiologists: Assessing Arousal Level during Induction, Maintenance, and Emergence. Anesthesiology. 2019;130:462–471. doi: 10.1097/ALN.0000000000002559.
    1. Schartner M, Seth A, Noirhomme Q, Boly M, Bruno MA, Laureys S, Barrett A. Complexity of Multi-Dimensional Spontaneous EEG Decreases during Propofol Induced General Anaesthesia. PLOS ONE. 2015;10:e0133532. doi: 10.1371/journal.pone.0133532.
    1. Schartner MM, Carhart-Harris RL, Barrett AB, Seth AK, Muthukumaraswamy SD. Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin. Scientific Reports. 2017;7:46421. doi: 10.1038/srep46421.
    1. Scheinin A, Kantonen O, Alkire M, Långsjö J, Kallionpää RE, Kaisti K, Radek L, Johansson J, Sandman N, Nyman M, Scheinin M, Vahlberg T, Revonsuo A, Valli K, Scheinin H. Foundations of Human Consciousness: Imaging the Twilight Zone. Journal of Neuroscience. 2021;41:1769–1778. doi: 10.1523/JNEUROSCI.0775-20.2020.
    1. Shortal BP, Hickman LB, Mak-McCully RA, Wang W, Brennan C, Ung H, Litt B, Tarnal V, Janke E, Picton P, Blain-Moraes S, Maybrier HR, Muench MR, Lin N, Avidan MS, Mashour GA, McKinstry-Wu AR, Kelz MB, Palanca BJ, Proekt A, ReCCognition Study Group Duration of EEG suppression does not predict recovery time or degree of cognitive impairment after general anaesthesia in human volunteers. British Journal of Anaesthesia. 2019;123:206–218. doi: 10.1016/j.bja.2019.03.046.
    1. Tucker AM, Whitney P, Belenky G, Hinson JM, Van Dongen HP. Effects of sleep deprivation on dissociated components of executive functioning. Sleep. 2010;33:47–57. doi: 10.1093/sleep/33.1.47.
    1. Usui N, Haji T, Maruyama M, Katsuyama N, Uchida S, Hozawa A, Omori K, Tsuji I, Kawashima R, Taira M. Cortical areas related to performance of WAIS Digit Symbol Test: a functional imaging study. Neuroscience Letters. 2009;463:1–5. doi: 10.1016/j.neulet.2009.07.048.
    1. Valentim AM, Alves HC, Olsson IA, Antunes LM. The effects of depth of isoflurane anesthesia on the performance of mice in a simple spatial learning task. Journal of the American Association for Laboratory Animal Science: JAALAS. 2008;47:16–19.
    1. Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003;26:117–126. doi: 10.1093/sleep/26.2.117.
    1. Van Dongen HPA, Dinges DF. Sleep, circadian rhythms, and psychomotor vigilance. Clinics in Sports Medicine. 2005;24:237–249. doi: 10.1016/j.csm.2004.12.007.
    1. Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AA. Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes. Lancet. 2015;385 Suppl 2:S11. doi: 10.1016/S0140-6736(15)60806-6.
    1. Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS, ENGAGES Research Group Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial. JAMA. 2019;321:473–483. doi: 10.1001/jama.2018.22005.
    1. Xie G, Deschamps A, Backman SB, Fiset P, Chartrand D, Dagher A, Plourde G. Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study. British Journal of Anaesthesia. 2011;106:548–557. doi: 10.1093/bja/aeq415.
    1. Zurek AA, Bridgwater EM, Orser BA. Inhibition of α5 γ-Aminobutyric acid type A receptors restores recognition memory after general anesthesia. Anesthesia and Analgesia. 2012;114:845–855. doi: 10.1213/ANE.0b013e31824720da.
    1. Zurek AA, Yu J, Wang DS, Haffey SC, Bridgwater EM, Penna A, Lecker I, Lei G, Chang T, Salter EW, Orser BA. Sustained increase in α5GABAA receptor function impairs memory after anesthesia. The Journal of Clinical Investigation. 2014;124:5437–5441. doi: 10.1172/JCI76669.

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