Characterization of phase transition in the thalamocortical system during anesthesia-induced loss of consciousness
Eunjin Hwang, Seunghwan Kim, Kyungreem Han, Jee Hyun Choi, Eunjin Hwang, Seunghwan Kim, Kyungreem Han, Jee Hyun Choi
Abstract
The thalamocortical system plays a key role in the breakdown or emergence of consciousness, providing bottom-up information delivery from sensory afferents and integrating top-down intracortical and thalamocortical reciprocal signaling. A fundamental and so far unanswered question for cognitive neuroscience remains whether the thalamocortical switch for consciousness works in a discontinuous manner or not. To unveil the nature of thalamocortical system phase transition in conjunction with consciousness transition, ketamine/xylazine was administered unobtrusively to ten mice under a forced working test with motion tracker, and field potentials in the sensory and motor-related cortex and thalamic nuclei were concomitantly collected. Sensory and motor-related thalamocortical networks were found to behave continuously at anesthesia induction and emergence, as evidenced by a sigmoidal response function with respect to anesthetic concentration. Hyperpolarizing and depolarizing susceptibility diverged, and a non-discrete change of transitional probability occurred at transitional regimes, which are hallmarks of continuous phase transition. The hyperpolarization curve as a function of anesthetic concentration demonstrated a hysteresis loop, with a significantly higher anesthetic level for transition to the down state compared to transition to the up state. Together, our findings concerning the nature of phase transition in the thalamocortical system during consciousness transition further elucidate the underlying basis for the ambiguous borderlines between conscious and unconscious brains. Moreover, our novel analysis method can be applied to systematic and quantitative handling of subjective concepts in cognitive neuroscience.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
References
- Laureys S, Owen AM, Schiff ND (2004) Brain function in coma, vegetative state, and related disorders. Lancet Neurol 3: 537–546.
- Boveroux P, Vanhaudenhuyse A, Bruno MA, Noirhomme Q, Lauwick S, et al. (2010) Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 113: 1038–1053.
- Ferrarelli F, Massimini M, Sarasso S, Casali A, Riedner BA, et al. (2010) Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness. Proc Natl Acad Sci U S A 107: 2681–2686.
- Alkire MT, Hudetz AG, Tononi G (2008) Consciousness and anesthesia. Science 322: 876–880.
- Steyn-Ross ML, Steyn-Ross DA, Sleigh JW (2004) Modelling general anaesthesia as a first-order phase transition in the cortex. Prog Biophys Mol Biol 85: 369–385.
- Liley DT, Bojak I (2005) Understanding the transition to seizure by modeling the epileptiform activity of general anesthetic agents. J Clin Neurophysiol 22: 300–313.
- Molaee-Ardekani B, Senhadji L, Shamsollahi MB, Vosoughi-Vahdat B, Wodey E (2007) Brain activity modeling in general anesthesia: enhancing local mean-field models using a slow adaptive firing rate. Phys Rev E Stat Nonlin Soft Matter Phys 76: 041911.
- Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262: 679–685.
- Llinas RR, Steriade M (2006) Bursting of thalamic neurons and states of vigilance. J Neurophysiol 95: 3297–3308.
- Edelman GM (2003) Naturalizing consciousness: a theoretical framework. Proc Natl Acad Sci U S A 100: 5520–5524.
- Hwang E, Kim S, Shin HS, Choi JH (2010) The forced walking test: a novel test for pinpointing the anesthetic-induced transition in consciousness in mouse. J Neurosci Methods 188: 14–23.
- Paxinos G, Franklin KBJ (2001) The Mouse Brain in Stereotaxic Coordinates. San Diego, CA: Academic Press.
- Schuttler J, Stanski DR, White PF, Trevor AJ, Horai Y, et al. (1987) Pharmacodynamic modeling of the EEG effects of ketamine and its enantiomers in man. J Pharmacokinet Biopharm 15: 241–253.
- Friedman EB, Sun Y, Moore JT, Hung HT, Meng QC, et al. (2010) A conserved behavioral state barrier impedes transitions between anesthetic-induced unconsciousness and wakefulness: evidence for neural inertia. PLoS One 5: e11903.
- Schwender D, Daunderer M, Mulzer S, Klasing S, Finsterer U, et al. (1996) Spectral edge frequency of the electroencephalogram to monitor “depth” of anaesthesia with isoflurane or propofol. Br J Anaesth 77: 179–184.
- Billard V, Gambus PL, Chamoun N, Stanski DR, Shafer SL (1997) A comparison of spectral edge, delta power, and bispectral index as EEG measures of alfentanil, propofol, and midazolam drug effect. Clin Pharmacol Ther 61: 45–58.
- Sleigh J, Steyn-Ross M, Steyn-Ross A, Voss L, Wilson M (2010) Anesthesia-Induced State Transitions in Neuronal Populations. In: Hudetz A, Pearce R, editors. Suppressing the Mind: Anesthetic Modulation of Memory and Consciousness. New York: Humana Press. 139–160.
- Gandomani MJ, Ghashghaii A, Tamadon A, Attaran HR, Behzadi MA, et al. (2011) Comparison of Anaesthetic Effects of Ketamine -Xylazine and Ketamine- Diazepam Combination in Budgerigar. Vet Scan 6: 81.
- Fosse RT, Grong K, Stangeland L, Lekven J (1987) Anesthetic interaction in cardiovascular research models: effects of xylazine and pentobarbital in cats. Am J Vet Res 48: 211–218.
- Alkire MT (2010) Anesthesia and the Thalamocortical System. In: Hudetz A, Pearce R, editors. Suppressing the Mind: Anesthetic Modulation of Memory and Consciousness. New York: Humana Press. 127–138.
- Hudetz AG (2006) Suppressing consciousness: Mechanisms of general anesthesia. Seminars in Anesthesia, Perioperative Medicine and Pain 25: 196–204.
- Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, et al. (2005) Breakdown of cortical effective connectivity during sleep. Science 309: 2228–2232.
Source: PubMed