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Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

André M Bastos, Jacob A Donoghue, Scott L Brincat and 8 more

eLife · 2021 · CC BY

doi:10.7554/elife.60824

Abstract

The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation ‘awakened’ anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.

References 76

  1. 1.

    Akaike H. A new look at the statistical model identification. IEEE Transactions on Automatic Control. 1974;19:716-723.

    Not in our library10.1109/tac.1974.1100705

  2. 2.

    Akeju O, Song AH, Hamilos AE, Pavone KJ, Flores FJ, Brown EN, Purdon PL. Electroencephalogram signatures of ketamine anesthesia-induced unconsciousness. Clinical Neurophysiology. 2016;127:2414-2422.

    Not in our library10.1016/j.clinph.2016.03.005

  3. 3.

    Aru J, Suzuki M, Rutiku R, Larkum ME, Bachmann T. Coupling the state and contents of consciousness. Frontiers in Systems Neuroscience. 2019;13:43.

    Not in our library10.3389/fnsys.2019.00043

  4. 4.
  5. 5.

    Bai D, Pennefather PS, MacDonald JF, Orser BA. The general anesthetic propofol slows deactivation and desensitization of GABA(A) receptors. The Neurosci. 1999;19:10635-10646.

    Not in our library10.1523/jneurosci.19-24-10635.1999

  6. 6.

    Baker JL, Ryou JW, Wei XF, Butson CR, Schiff ND, Purpura KP. Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates. Journal of Neurophysiology. 2016;116:2383-2404.

    Not in our library10.1152/jn.01129.2015

  7. 7.

    Bastos AM, Briggs F, Alitto HJ, Mangun GR, Usrey WM. Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations. Journal of Neuroscience. 2014;34:7639-7644.

    Not in our library10.1523/jneurosci.4216-13.2014

  8. 8.

    Bastos AM, Vezoli J, Bosman CA, Schoffelen JM, Oostenveld R, Dowdall JR, De Weerd P, Kennedy H, Fries P. Visual Areas exert feedforward and feedback influences through distinct frequency channels. Neuron. 2015;85:390-401.

    Not in our library10.1016/j.neuron.2014.12.018

  9. 9.

    Bastos AM, Loonis R, Kornblith S, Lundqvist M, Miller EK. Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory. PNAS. 2018;115:1117-1122.

    Not in our library10.1073/pnas.1710323115

  10. 10.

    Bastos AM, Lundqvist M, Waite AS, Kopell N, Miller EK. Layer and rhythm specificity for predictive routing. PNAS. 2020;117:31459-31469.

    Not in our library10.1073/pnas.2014868117

  11. 11.

    Boly M, Massimini M, Tsuchiya N, Postle BR, Koch C, Tononi G. Are the neural correlates of consciousness in the front or in the back of the cerebral cortex? clinical and neuroimaging evidence. The Journal of Neuroscience. 2017;37:9603-9613.

    Not in our library10.1523/jneurosci.3218-16.2017

  12. 12.

    Brown EN, Barbieri R, Ventura V, Kass RE, Frank LM. The time-rescaling theorem and its application to neural spike train data analysis. Neural Computation. 2002;14:325-346.

    Not in our library10.1162/08997660252741149

  13. 13.

    Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and Coma. New England Journal of Medicine. 2010;363:2638-2650.

    Not in our library10.1056/nejmra0808281

  14. 14.

    Brown EN, Purdon PL, Van Dort CJ. General anesthesia and altered states of arousal: a systems neuroscience analysis. Annual Review of Neuroscience. 2011;34:601-628.

    Not in our library10.1146/annurev-neuro-060909-153200

  15. 15.

    Brown EN, Pavone KJ, Naranjo M. Multimodal general anesthesia: theory and practice. Anesthesia and Analgesia. 2018;127:1246-1258.

    Not in our library10.1213/ane.0000000000003668

  16. 16.

    Buschman TJ, Miller EK. Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices. Science. 2007;315:1860-1862.

    Not in our library10.1126/science.1138071

  17. 17.

    Chemali JJ, Van Dort CJ, Brown EN, Solt K. Active emergence from propofol general anesthesia is induced by methylphenidate. Anesthesiology. 2012;116:998-1005.

    Not in our library10.1097/aln.0b013e3182518bfc

  18. 18.

    Ching S, Cimenser A, Purdon PL, Brown EN, Kopell NJ. Thalamocortical model for a propofol-induced alpha-rhythm associated with loss of consciousness. PNAS. 2010;107:22665-22670.

    Not in our library10.1073/pnas.1017069108

  19. 19.

    Cimenser A, Purdon PL, Pierce ET, Walsh JL, Salazar-Gomez AF, Harrell PG, Tavares-Stoeckel C, Habeeb K, Brown EN. Tracking brain states under general anesthesia by using global coherence analysis. PNAS. 2011;108:8832-8837.

    Not in our library10.1073/pnas.1017041108

  20. 20.

    Crick F, Koch C. Towards a neurobiological theory of consciousness. Seminars in the Neurosciences. 1990;2:263-275.

    Not in our library

  21. 21.

    Czanner G, Eden UT, Wirth S, Yanike M, Suzuki WA, Brown EN. Analysis of between-trial and within-trial neural spiking dynamics. Journal of Neurophysiology. 2008;99:2672-2693.

    Not in our library10.1152/jn.00343.2007

  22. 22.

    Czanner G, Sarma SV, Ba D, Eden UT, Wu W, Eskandar E, Lim HH, Temereanca S, Suzuki WA, Brown EN. Measuring the signal-to-noise ratio of a neuron. PNAS. 2015;112:7141-7146.

    Not in our library10.1073/pnas.1505545112

  23. 23.

    DeGroot MH, Schervish MJ. Probability and Statistics. 2012.

    Not in our library

  24. 24.

    Dehaene S. Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition. 2001;79:1-37.

    Not in our library10.1016/s0010-0277(00)00123-2

  25. 25.

    Dehaene S, Changeux JP. Experimental and theoretical approaches to conscious processing. Neuron. 2011;70:200-227.

    Not in our library10.1016/j.neuron.2011.03.018

  26. 26.

    Demertzi A, Tagliazucchi E, Dehaene S, Deco G, Barttfeld P, Raimondo F, Martial C, Fernández-Espejo D, Rohaut B, Voss HU, Schiff ND, Owen AM, Laureys S, Naccache L, Sitt JD. Human consciousness is supported by dynamic complex patterns of brain signal coordination. Science Advances. 2019;5:eaat7603.

    Not in our library10.1126/sciadv.aat7603

  27. 27.

    Dempster AP, Laird NM, Rubin DB. Maximum likelihood from incomplete data via the EM algorithm. Journal of the Royal Statistical Society Series B. 1977;39:1-38.

    Not in our library10.1111/j.2517-6161.1977.tb01600.x

  28. 28.

    Eldar YC, Oppenheim AV. MMSE whitening and subspace whitening. IEEE Transactions on Information Theory. 2003;49:1846-1851.

    Not in our library10.1109/tit.2003.813507

  29. 29.

    Engel AK, Fries P, König P, Brecht M, Singer W. Temporal binding, binocular rivalry, and consciousness. Consciousness and Cognition. 1999;8:128-151.

    Not in our library10.1006/ccog.1999.0389

  30. 30.
  31. 31.

    Fiebelkorn IC, Kastner S. A rhythmic theory of attention. Trends in Cognitive Sciences. 2019;23:87-101.

    Not in our library10.1016/j.tics.2018.11.009

  32. 32.

    Flores FJ, Hartnack KE, Fath AB, Kim SE, Wilson MA, Brown EN, Purdon PL. Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness. PNAS. 2017;114:E6660-E6668.

    Not in our library10.1073/pnas.1700148114

  33. 33.

    Halassa MM, Sherman SM. Thalamocortical circuit motifs: a general framework. Neuron. 2019;103:762-770.

    Not in our library10.1016/j.neuron.2019.06.005

  34. 34.

    Hapfelmeier G, Schneck H, Kochs E. Sevoflurane potentiates and blocks GABA-induced currents through recombinant alpha1beta2gamma2 GABAA receptors: implications for an enhanced GABAergic transmission. European Journal of Anaesthesiology. 2001;18:377-383.

    Not in our library10.1046/j.0265-0215.2001.00848.x

  35. 35.

    Hemmings HC, Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends in Pharmacological Sciences. 2005;26:503-510.

    Not in our library10.1016/j.tips.2005.08.006

  36. 36.

    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.

    Not in our library10.1016/j.tips.2019.05.001

  37. 37.

    Jones EG. The Thalamus. 2007.

    Not in our library

  38. 38.

    Kenny JD, Taylor NE, Brown EN, Solt K. Dextroamphetamine (but not atomoxetine) Induces reanimation from general anesthesia: implications for the roles of dopamine and norepinephrine in active emergence. PLOS ONE. 2015;10:e0131914.

    Not in our library10.1371/journal.pone.0131914

  39. 39.

    Komarek P, Moore AW. Making logistic regression a core data mining tool with TR-IRLSFifth IEEE international conference on data mining (ICDM’05). 2005.

    Not in our library

  40. 40.

    Lakatos P, Karmos G, Mehta AD, Ulbert I, Schroeder CE. Entrainment of neuronal oscillations as a mechanism of attentional selection. Science. 2008;320:110-113.

    Not in our library10.1126/science.1154735

  41. 41.

    Lee U, Ku S, Noh G, Baek S, Choi B, Mashour GA. Disruption of frontal-parietal communication by ketamine, propofol, and sevoflurane. Anesthesiology. 2013;118:1264-1275.

    Not in our library10.1097/aln.0b013e31829103f5

  42. 42.

    Lewis LD, Weiner VS, Mukamel EA, Donoghue JA, Eskandar EN, Madsen JR, Anderson WS, Hochberg LR, Cash SS, Brown EN, Purdon PL. Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness. PNAS. 2012;109:E3377-E3386.

    Not in our library10.1073/pnas.1210907109

  43. 43.

    Llinás R, Ribary U, Contreras D, Pedroarena C. The neuronal basis for consciousness. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 1998;353:1841-1849.

    Not in our library10.1098/rstb.1998.0336

  44. 44.

    Llinás R. Consciousness and the thalamocortical loop. 2003;409-416.

    Not in our library

  45. 45.

    Manly BFJ. Randomization, Bootstrap and Monte Carlo Methods in Biology. 2018.

    Not in our library

  46. 46.

    Maris E, Oostenveld R. Nonparametric statistical testing of EEG- and MEG-data. Journal of Neuroscience Methods. 2007;164:177-190.

    Not in our library10.1016/j.jneumeth.2007.03.024

  47. 47.

    McCarley RW. Neurobiology of REM and NREM sleep. Sleep Medicine. 2007;8:302-330.

    Not in our library10.1016/j.sleep.2007.03.005

  48. 48.

    McCarthy MM, Brown EN, Kopell N. Potential network mechanisms mediating electroencephalographic beta rhythm changes during propofol-induced paradoxical excitation. Journal of Neuroscience. 2008;28:13488-13504.

    Not in our library10.1523/jneurosci.3536-08.2008

  49. 49.

    McCullagh P, Nelder J. Generalized Linear Models. 1989.

    Not in our library

  50. 50.

    McLaren DG, Kosmatka KJ, Oakes TR, Kroenke CD, Kohama SG, Matochik JA, Ingram DK, Johnson SC. A population-average MRI-based atlas collection of the rhesus macaque. NeuroImage. 2009;45:52-59.

    Not in our library10.1016/j.neuroimage.2008.10.058

  51. 51.

    Miller EK, Lundqvist M, Bastos AM. Working memory 2.0. Neuron. 2018;100:463-475.

    Not in our library10.1016/j.neuron.2018.09.023

  52. 52.

    Muindi F, Kenny JD, Taylor NE, Solt K, Wilson MA, Brown EN, Van Dort CJ. Electrical stimulation of the parabrachial nucleus induces reanimation from isoflurane general anesthesia. Behavioural Brain Research. 2016;306:20-25.

    Not in our library10.1016/j.bbr.2016.03.021

  53. 53.

    Mulliken GH, Bichot NP, Ghadooshahy A, Sharma J, Kornblith S, Philcock M, Desimone R. Custom-fit radiolucent cranial implants for neurophysiological recording and stimulation. Journal of Neuroscience Methods. 2015;241:146-154.

    Not in our library10.1016/j.jneumeth.2014.12.011

  54. 54.
  55. 55.

    Palva S, Palva JM. New vistas for alpha-frequency band oscillations. Trends in Neurosciences. 2007;30:150-158.

    Not in our library10.1016/j.tins.2007.02.001

  56. 56.

    Pavone KJ, Akeju O, Sampson AL, Ling K, Purdon PL, Brown EN. Nitrous oxide-induced slow and Delta oscillations. Clinical Neurophysiology. 2016;127:556-564.

    Not in our library10.1016/j.clinph.2015.06.001

  57. 57.

    Pillay S, Liu X, Baracskay P, Hudetz AG. Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats. Brain Connectivity. 2014;4:523-534.

    Not in our library10.1089/brain.2014.0254

  58. 58.

    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.

    Not in our library10.1073/pnas.1221180110

  59. 59.

    Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical electroencephalography for anesthesiologists. Anesthesiology. 2015;123:937-960.

    Not in our library10.1097/aln.0000000000000841

  60. 60.

    Redinbaugh MJ, Phillips JM, Kambi NA, Mohanta S, Andryk S, Dooley GL, Afrasiabi M, Raz A, Saalmann YB. Thalamus modulates consciousness via Layer-Specific control of cortex. Neuron. 2020;106:66-75.

    Not in our library10.1016/j.neuron.2020.01.005

  61. 61.

    Saalmann YB, Pinsk MA, Wang L, Li X, Kastner S. The pulvinar regulates information transmission between cortical Areas based on attention demands. Science. 2012;337:753-756.

    Not in our library10.1126/science.1223082

  62. 62.

    Saalmann YB, Kastner S. The cognitive thalamus. Frontiers in Systems Neuroscience. 2015;9:39.

    Not in our library10.3389/fnsys.2015.00039

  63. 63.

    Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O'Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007;448:600-603.

    Not in our library10.1038/nature06041

  64. 64.

    Sherman SM. Thalamus plays a central role in ongoing cortical functioning. Nature Neuroscience. 2016;19:533-541.

    Not in our library10.1038/nn.4269

  65. 65.

    Shumway RH, Stoffer DS. An approach to time series smoothing and forecasting using the em algorithm. Journal of Time Series Analysis. 1982;3:253-264.

    Not in our library10.1111/j.1467-9892.1982.tb00349.x

  66. 66.

    Smith AC, Stefani MR, Moghaddam B, Brown EN. Analysis and design of behavioral experiments to characterize population learning. Journal of Neurophysiology. 2005;93:1776-1792.

    Not in our library10.1152/jn.00765.2004

  67. 67.

    Solt K, Cotten JF, Cimenser A, Wong KF, Chemali JJ, Brown EN. Methylphenidate actively induces emergence from general anesthesia. Anesthesiology. 2011;115:791-803.

    Not in our library10.1097/aln.0b013e31822e92e5

  68. 68.

    Solt K, Van Dort CJ, Chemali JJ, Taylor NE, Kenny JD, Brown EN. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology. 2014;121:311-319.

    Not in our library10.1097/aln.0000000000000117

  69. 69.

    Taylor NE, Chemali JJ, Brown EN, Solt K. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology. 2013;118:30-39.

    Not in our library10.1097/aln.0b013e318278c896

  70. 70.

    Taylor NE, Van Dort CJ, Kenny JD, Pei J, Guidera JA, Vlasov KY, Lee JT, Boyden ES, Brown EN, Solt K. Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. PNAS. 2016;113:12826-12831.

    Not in our library10.1073/pnas.1614340113

  71. 71.

    Tinker JH, Sharbrough FW, Michenfelder JD. Anterior shift of the dominant EEG rhytham during anesthesia in the Java monkey: correlation with anesthetic potency. Anesthesiology. 1977;46:252-259.

    Not in our library10.1097/00000542-197704000-00005

  72. 72.

    Tononi G, Boly M, Massimini M, Koch C. Integrated information theory: from consciousness to its physical substrate. Nature Reviews Neuroscience. 2016;17:450-461.

    Not in our library10.1038/nrn.2016.44

  73. 73.

    Truccolo W, Eden UT, Fellows MR, Donoghue JP, Brown EN. A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects. Journal of Neurophysiology. 2005;93:1074-1089.

    Not in our library10.1152/jn.00697.2004

  74. 74.

    Vijayan S, Ching S, Purdon PL, Brown EN, Kopell NJ. Thalamocortical mechanisms for the anteriorization of α rhythms during propofol-induced unconsciousness. Journal of Neuroscience. 2013;33:11070-11075.

    Not in our library10.1523/jneurosci.5670-12.2013

  75. 75.

    Vinck M, van Wingerden M, Womelsdorf T, Fries P, Pennartz CM. The pairwise phase consistency: a bias-free measure of rhythmic neuronal synchronization. NeuroImage. 2010;51:112-122.

    Not in our library10.1016/j.neuroimage.2010.01.073

  76. 76.

    Wu CW, Kaas JH. Reorganization in primary motor cortex of primates with Long-Standing therapeutic amputations. The Journal of Neuroscience. 1999;19:7679-7697.

    Not in our library10.1523/jneurosci.19-17-07679.1999

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