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

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.
   Global Workspace Dynamics: Cortical “Binding and Propagation” Enables Conscious Contents · 2013

   No notice
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.
    The mediodorsal pulvinar coordinates the macaque fronto-parietal network during rhythmic spatial attention · 2019

    No notice
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

Cited by papers we hold 2

• A human brain network linked to restoration of consciousness after deep brain stimulation · 2025
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• Deep brain stimulation of the thalamus restores signatures of consciousness in a nonhuman primate model · 2022
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