Skip to main content
SpringerLink
Log in

A Mesoscopic Modelling Approach to Anaesthetic Action on Brain Electrical Activity

  • Chapter
Sleep and Anesthesia

Part of the book series: Springer Series in Computational Neuroscience ((NEUROSCI,volume 15))

Abstract

Relating the measurable, large scale, effects of anaesthetic agents to their molecular and cellular targets of action is necessary to better understand the principles by which they affect behavior, as well as enabling the design and evaluation of more effective agents and the better clinical monitoring of existing and future drugs. Volatile and intravenous general anaesthetic agents (GAs) are now known to exert their effects on a variety of protein targets, the most important of which seem to be the neuronal ion channels. It is hence unlikely that anaesthetic effect is the result of a unitary mechanism at the single cell level. However, by altering the behavior of ion channels GAs are believed to change the overall dynamics of distributed networks of neurons. This disruption of regular network activity can be hypothesized to cause the hypnotic and analgesic effects of GAs and may well present more stereotypical characteristics than its underlying microscopic causes. Nevertheless, there have been surprisingly few theories that have attempted to integrate, in a quantitative manner, the empirically well documented alterations in neuronal ion channel behavior with the corresponding macroscopic effects. Here we outline one such approach, and show that a range of well documented effects of anaesthetics on the electroencephalogram (EEG) may be putatively accounted for. In particular we parametrize, on the basis of detailed empirical data, the effects of halogenated volatile ethers (a clinically widely used class of general anaesthetic agent). The resulting model is able to provisionally account for a range of anaesthetically induced EEG phenomena that include EEG slowing, biphasic changes in EEG power, and the dose dependent appearance of anomalous ictal activity, as well as providing a basis for novel approaches to monitoring brain function in both health and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    However, recently there has been renewed interest in such theories, because of the apparent invariance across a range of vertebrates of the concentrations of inhaled anaesthetic agents required to extinguish the response to noxious (painful) stimuli (Eger et al. 2008). The ability of anaesthetic agents to induce such immobility is, together with hypnosis and analgesia, a cardinal feature of anaesthesia. While it is reasonably well established that immobility is mediated at the level of the spinal chord, no present consensus holds regarding the corresponding molecular targets. Because of their ubiquitous phylogenetic potency, evolutionarily highly conserved cellular and/or molecular loci seem necessary (Sonner 2008). It has been suggested that volatile anaesthetics affect highly conserved sodium channels through a nonspecific mechanism, such as being adsorbed into the membrane, with a subsequent alteration of the function of the resident sodium channels and other membrane-bound proteins (Cantor 1997). This is an interesting hypothesis, but difficult to test experimentally: sodium channels are everywhere in the central nervous system and are involved in a wide variety of processes that may, or may not be, relevant to understanding volatile anaesthetic effect, e.g., the genesis of the action potential, presynaptic neurotransmitter release and the postsynaptic actions of a range of excitatory neurotransmitters and neuromodulators such as glutamate and acetylcholine.

  2. 2.

    This is achieved through the targeted expression, by the viral transfection, of a light-sensitive bacteriorhodopsin—a cation selective ion channel specifically activated by blue light.

References

  • Alkire MT, Hudetz AG, Tononi G (2008) Consciousness and anesthesia. Science 322:876–880

    Article  PubMed  CAS  Google Scholar 

  • Amari S (1975) Homogeneous nets of neuron-like elements. Biol Cybern 17:211–220

    Article  PubMed  CAS  Google Scholar 

  • Bayliss DA, Barrett PQ (2008) Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci 29:566–575

    Article  PubMed  CAS  Google Scholar 

  • Belelli D, Harrison NL, Maguire J, Macdonald RL, Walker MC, Cope DW (2009) Extrasynaptic GABAA receptors: form, pharmacology, and function. J Neurosci 29(41):12757–12763

    Article  PubMed  CAS  Google Scholar 

  • Bertz RJ, Kroboth PD, Kroboth FJ, Reynolds IJ, Salek F, Wright CE, Smith RB (1997) Alprazolam in young and elderly men: sensitivity and tolerance to psychomotor, sedative and memory effects. J Pharmacol Exp Ther 281:1317–1329

    PubMed  CAS  Google Scholar 

  • Bojak I, Liley DTJ (2005) Modeling the effects of anesthesia on the electroencephalogram. Phys Rev E 71:041902

    Article  CAS  Google Scholar 

  • Bojak I, Liley DTJ (2007) Self-organized 40 Hz synchronization in a physiological theory of EEG. Neurocomputing 70:2085–2090

    Article  Google Scholar 

  • Bojak I, Liley DTJ (2010) Axonal velocity distributions in neural field equations. PLoS Comput Biol 6(1):e1000653

    Article  PubMed  Google Scholar 

  • Bojak I, Oostendorp TF, Reid AT, Kotter R (2010) Connecting mean field models of neural activity to EEG and fMRI data. Brain Topogr 23:139–149

    Article  PubMed  Google Scholar 

  • Bower J, Beeman D (1998) The book of GENESIS: exploring realistic neural models with the GEneral NEural SImulation system, 2nd edn. Springer, New York

    Google Scholar 

  • Breimer LT, Hennis PJ, Burm AG, Danhof M, Bovill JG, Spierdijk J, Vletter AA (1990) Quantification of the EEG effect of midazolam by aperiodic analysis in volunteers. Pharmacokinetic-pharmacodynamic modelling. Clin Pharmacokinet 18:245–253

    Article  PubMed  CAS  Google Scholar 

  • Bruhn J, Bouillon T, Shafer S (2000) Bispectral index (BIS) and burst suppression: revealing a part of the bis algorithm. J Clin Monit Comput 16:593–596

    Article  PubMed  CAS  Google Scholar 

  • Campagna JA, Miller KW, Forman SA (2003) Mechanisms of actions of inhaled anesthetics. N Engl J Med 348:2110–2124

    Article  PubMed  CAS  Google Scholar 

  • Cantor RS (1997) The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 36:2339–2344

    Article  PubMed  CAS  Google Scholar 

  • Cardin JA, Carlen M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:663–667

    Article  PubMed  CAS  Google Scholar 

  • Dafilis MP, Liley DTJ, Cadusch PJ (2001) Robust chaos in a model of the electroencephalogram: implications for brain dynamics. Chaos 11:474–478

    Article  PubMed  Google Scholar 

  • Deco G, Jirsa VK, Robinson PA, Breakspear M, Friston K (2008) The dynamic brain: from spiking neurpons to neural masses and cortical fields. PLoS Comput Biol 4(8):e1000092

    Article  PubMed  Google Scholar 

  • Eger EE, Raines DE, Shafer SL, Hemmings HC, Sonner JM (2008) Is a new paradigm needed to explain how inhaled anesthetics produce immobility? Anesth Analg 107:832–848

    Article  PubMed  Google Scholar 

  • Eilers PHC, Goeman JJ (2004) Enhancing scatterplots with smoothed densities. Bioinformatics 20:623–628

    Article  PubMed  CAS  Google Scholar 

  • Ermentout B (1998) Neural networks as spatio-temporal pattern-forming systems. Rep Prog Phys 61:353–430

    Article  Google Scholar 

  • Feshchenko VA, Veselis RA, Reinsel RA (2004) Propofol-induced alpha rhythm. Neuropsychobiology 50(3):257–266

    Article  PubMed  CAS  Google Scholar 

  • Franks NP (2008) General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 9:370–386

    Article  PubMed  CAS  Google Scholar 

  • Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367:607–614

    Article  PubMed  CAS  Google Scholar 

  • Freeman WJ (1975) Mass action in the nervous system. Academic Press, New York

    Google Scholar 

  • Grasshoff C, Rudolph U, Antkowiak B (2005) Molecular and systemic mechanisms of general anaesthesia: the ‘multi-site and multiple mechanisms’ concept. Curr Op Anaesthesiol 18(4):386–391

    Article  Google Scholar 

  • Gugino LD, Chabot RJ, Prichep LS, John ER, Formanek V, Aglio LS (2001) Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane. Br J Anaesth 87:421–428

    Article  PubMed  CAS  Google Scholar 

  • Hemmings HC, Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL (2005) Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 26(10):503–511

    Article  PubMed  CAS  Google Scholar 

  • Hines ML, Carnevale NT (2001) NEURON: a tool for neuroscientists. Neuroscientist 7:123–135

    Article  PubMed  CAS  Google Scholar 

  • Hotz MA, Ritz R, Linder L, Scollo-Lavizzari G, Haefeli WE (2000) Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects. Br J Clin Pharmacol 49:72–79

    Article  PubMed  CAS  Google Scholar 

  • Ishizawa Y (2007) Mechanisms of anesthetic actions and the brain. J Anesth 21(2):187–199

    Article  PubMed  Google Scholar 

  • Jeleazcov CH, Schwilden H (2003) Bispectral analysis does not differentiate between anaesthesia EEG and a linear random process. Biomed Tech (Berl) 48:269–274

    Article  Google Scholar 

  • Jevtovic-Todorovic V, Todorovic SM, Mennerick S, Powell S, Dikranian K, Benshoff N, Zorumski CF, Olney JW (1998) Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4:460–463

    Article  PubMed  CAS  Google Scholar 

  • Jirsa VK, Haken H (1996) Field theory of electromagnetic brain activity. Phys Rev Lett 77:960–963

    Article  PubMed  CAS  Google Scholar 

  • John ER, Prichep LS, Kox W, Valdes-Sosa P, Bosch-Bayard J, Aubert E, Tom M, diMichele F, Gugino LD (2001) Invariant reversible qEEG effects of anesthetics. Conscious Cogn 10:165–183

    Article  PubMed  CAS  Google Scholar 

  • Koblin D, Chortkoff B, Laster M, Eger E, Halsey M, Ionescu P (1994) Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 79:1043–1048

    Article  PubMed  CAS  Google Scholar 

  • Kohn LT, Corrigan JM, Donaldson MS (eds) (2000) Building a safer health system. National Academy Press, Washington

    Google Scholar 

  • Koskinen M, Mustola S, Seppanen T (2005) Relation of EEG spectrum progression to loss of responsiveness during induction of anesthesia with propofol. Clin Neurophysiol 116:2069–2076

    Article  PubMed  CAS  Google Scholar 

  • Kuizenga K, Kalkman C, Hennis P (1998) Quantitative electroencephalographic analysis of the biphasic concentration-effect relationship of propofol in surgical patients during extradural analgesia. Br J Anaesth 80:725–732

    PubMed  CAS  Google Scholar 

  • Kuizenga K, Wierda J, Kalkman C (2001) Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane. Br J Anaesth 86:354–360

    Article  PubMed  CAS  Google Scholar 

  • Liley DTJ, Cadusch P, Wright J (1999) A continuum theory of electro-cortical activity. Neurocomputing 26–27:795–800

    Article  Google Scholar 

  • Liley DTJ, Cadusch P, Dafilis M (2002) A spatially continuous mean field theory of electrocortical activity. Net Comput Neural Syst 13:67–113

    Google Scholar 

  • Liley DTJ, Cadusch P, Gray M, Nathan P (2003) Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity. Phys Rev E 68:051,906

    Article  Google Scholar 

  • Liley DTJ, Sinclair N, Lipping T, Heyse B, Vereecke E, Struys M (2010) Propofol and remifentanil differentially modulate frontal electroencephalographic activity. Anesthesiology 113:1–13

    Article  Google Scholar 

  • Liley DTJ, Leslie K, Sinclair NC, Feckie M (2008) Dissociating the effects of nitrous oxide on brain electrical activity using fixed order time series modeling. Comput Biol Med 38:1121–1130

    Article  PubMed  CAS  Google Scholar 

  • Macdonald RL (1994) GABA-A receptor channels. Annu Rev Neurosci 17:569–602

    Article  PubMed  CAS  Google Scholar 

  • Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL (1997) Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 389:385–389

    Article  PubMed  CAS  Google Scholar 

  • Mohler H, Fritsschy JM, Lüscher B, Rudolph U, Benson J (1996) The GABAA receptors: from subunits to diverse functions. In: Narahashi T (ed) Ion channels, vol 4. Plenum, New York, pp 89–113

    Google Scholar 

  • Nunez PL (1974) The brain wave equation: a model for the EEG. Math Biosci 21:279–297

    Article  Google Scholar 

  • Nunez PL (1981) Electric fields of the brain: The neurophysics of EEG, 1st edn. Oxford University Press, New York

    Google Scholar 

  • Pawelzik H, Bannister AP, Deuchars J, Illia M, Thomson AM (1999) Modulation of bistratified cell IPSPs and basket cell IPSPs by pentobarbitine sodium, diazepam and Zn2+: dual recordings in slices of adult rant hippocampus. Eur J Neurosci 11:3552–3564

    Article  PubMed  CAS  Google Scholar 

  • Rampil IJ (1998) A primer for EEG signal processing in anesthesia. Anesthesiology 89(4):980–1002

    Article  PubMed  CAS  Google Scholar 

  • Robinson PA, Rennie CJ, Wright JJ (1997) Propagation and stability of waves of electrical activity in the cerebral cortex. Phys Rev E 56:826–840

    Article  CAS  Google Scholar 

  • Robinson PA, Rennie CJ, Wright JJ, Bahramali H, Gordon E, Rowe DL (2001) Prediction of electroencephalographic spectra from neurophysiology. Phys Rev E 63:021903

    Article  CAS  Google Scholar 

  • Rudolph U, Antkowiak B (2004) Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 5:709–720

    Article  PubMed  CAS  Google Scholar 

  • Schwilden H, Jeleazcov C (2002) Does the EEG during isoflurane/alfentanil anesthesia differ from linear random data? J Clin Monit Comput 17:449–457

    Article  PubMed  Google Scholar 

  • Solt K, Eger EI, Raines DE (2006) Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics. Anesth Analg 102:1407–1411

    Article  PubMed  CAS  Google Scholar 

  • Sonner JM (2008) A hypothesis on the origin and evolution of the response to inhaled anesthetics. Anesth Analg 107:849–854

    Article  PubMed  Google Scholar 

  • Stam CJ, Pijn JP, Suffczynski P, Lopes da Silva FH (1999) Dynamics of the human alpha rhythm: evidence for non-linearity? Clin Neurophysiol 110:1801–1813

    Article  PubMed  CAS  Google Scholar 

  • Swindale NV (2003) Neural synchrony, axonal path lengths and general anesthesia: a hypothesis. Neuroscientist 9:440–445

    Article  PubMed  Google Scholar 

  • Tuckwell HC (1988) Introduction to theoretical neurobiology. Linear cable theory and dendritic structure, vol 1. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • van Rotterdam A, Lopes da Silva FH, van den Ende J, Viergever MA, Hermans AJ (1982) A model of the spatial-temporal characteristics of the alpha rhythm. Bull Math Biol 44:283–305

    Article  PubMed  Google Scholar 

  • Violet JM, Downie DL, Nakisa RC, Lieb WR, Franks NP (1997) Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology 86:866–874

    Article  PubMed  CAS  Google Scholar 

  • Wilson H, Cowan J (1972) Excitatory and inhibitory interactions in localized populations of model neuron. Biophys J 12:1–24

    Article  PubMed  CAS  Google Scholar 

  • Wilson H, Cowan J (1973) A mathematical theory of the functional dynamics of cortical and thalamic nervous tissue. Kybernetik 13:55–80

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Brain and Psychological Sciences Research Centre (BPsyC), Swinburne University of Technology, P.O. Box 218, Hawthorn, VIC, 3122, Australia

    D. T. J. Liley

  2. Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA

    B. L. Foster

  3. School of Psychology (CN-CR), University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    I. Bojak

Authors
  1. D. T. J. Liley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. L. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Bojak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. T. J. Liley .

Editor information

Editors and Affiliations

  1. Equipe Cortex, INRIA CR Nancy, rue du Jardin Botanique 615, Villers-lès-Nancy CX, 54602, France

    Axel Hutt

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Liley, D.T.J., Foster, B.L., Bojak, I. (2011). A Mesoscopic Modelling Approach to Anaesthetic Action on Brain Electrical Activity. In: Hutt, A. (eds) Sleep and Anesthesia. Springer Series in Computational Neuroscience, vol 15. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0173-5_7

Download citation

Publish with us

Policies and ethics

Search

Navigation