Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy

[en] Background: Impaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. Methods: Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time–frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions. Results: Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha–gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni corrected). Conclusions: Propofol-induced loss of consciousness is associated with impaired hierarchical feedforward connectivity assessed by EEG after occipital TMS. © 2018 British Journal of Anaesthesia

Disciplines :

Neurosciences & behavior

Author, co-author :

Sanders, R. D.; Department of Anesthesiology, University of Wisconsin, Madison, WI, United States

Banks, M. I.; Department of Anesthesiology, University of Wisconsin, Madison, WI, United States

Darracq, M.; Department of Anesthesiology, University of Wisconsin, Madison, WI, United States

Moran, R.; Faculty of Engineering, University of Bristol, Bristol, United Kingdom

Sleigh, J.; Department of Anaesthesia, Waikato Hospital, Hamilton, New Zealand

Gosseries, Olivia ; Université de Liège - ULiège > GIGA : Coma Group

BONHOMME, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Département d'Anesthésie et réanimation > Service d'anesthésie - réanimation

Brichant, Jean-François ; Université de Liège - ULiège > Département des sciences cliniques > Anesthésie et réanimation

Rosanova, Mario; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

Raz, A.; Department of Anesthesiology, University of Wisconsin, Madison, WI, United States, Rambam Healthcare Campus, Haifa, Israel

More authors (4 more)

Language :

English

Title :

Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy

Publication date :

2018

Journal title :

British Journal of Anaesthesia

ISSN :

0007-0912

eISSN :

1471-6771

Publisher :

Elsevier Ltd

Volume :

121

Issue :

Pages :

1084-1096

Peer reviewed :

Peer Reviewed verified by ORBi

European Projects :

H2020 - 720270 - HBP SGA1 - Human Brain Project Specific Grant Agreement 1

Name of the research project :

ARC-06/11-340

Funders :

Orion Pharma
Philips Healthcare
University of Wisconsin
NIH - National Institutes of Health [US-MD]
Italian Ministry of Health
JSMF - James S McDonnell Foundation [US-MO]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
MSF - Mind Science Foundation [US-TX]
FWB - Fédération Wallonie-Bruxelles [BE]
ULiège - Université de Liège [BE]
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
CE - Commission Européenne [BE]

Available on ORBi :

since 04 January 2019

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Bibliography

Casali, A.G., Gosseries, O., Rosanova, M., et al. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Trans Med, 5, 2013, 198ra05.
Ferrarelli, F., Massimini, M., Sarasso, S., et al. Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness. Proc Natl Acad Sci U S A 107 (2010), 2681–2686.
Massimini, M., Ferrarelli, F., Huber, R., Esser, S.K., Singh, H., Tononi, G., Breakdown of cortical effective connectivity during sleep. Science 309 (2005), 2228–2232.
Rosanova, M., Gosseries, O., Casarotto, S., et al. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain 135 (2012), 1308–1320.
Sarasso, S., Boly, M., Napolitani, M., et al. Consciousness and complexity during unresponsiveness induced by propofol, xenon, and ketamine. Curr Biol 25 (2015), 3099–3105.
Sanders, R.D., Tononi, G., Laureys, S., Sleigh, J.W., Unresponsiveness ≠ unconsciousness. Anesthesiology 116 (2012), 946–959.
Tononi, G., Boly, M., Massimini, M., Koch, C., Integrated information theory: from consciousness to its physical substrate. Nat Rev Neurosci 17 (2016), 450–461.
Tononi, G., An information integration theory of consciousness. BMC Neurosci, 5, 2004, 42.
Imas, O.A., Ropella, K.M., Ward, B.D., Wood, J.D., Hudetz, A.G., Volatile anesthetics disrupt frontal–posterior recurrent information transfer at gamma frequencies in rat. Neurosci Lett 387 (2005), 145–150.
Peltier, S.J., Kerssens, C., Hamann, S.B., Sebel, P.S., Byas-Smith, M., Hu, X., Functional connectivity changes with concentration of sevoflurane anesthesia. Neuroreport 16 (2005), 285–288.
Alkire, M.T., Loss of effective connectivity during general anesthesia. Int Anesthesiol Clin 46 (2008), 55–73.
Lee, U., Kim, S., Noh, G.J., Choi, B.M., Hwang, E., Mashour, G.A., The directionality and functional organization of frontoparietal connectivity during consciousness and anesthesia in humans. Conscious Cogn 18 (2009), 1069–1078.
Ku, S.W., Lee, U., Noh, G.J., Jun, I.G., Mashour, G.A., Preferential inhibition of frontal-to-parietal feedback connectivity is a neurophysiologic correlate of general anesthesia in surgical patients. PLoS One, 6, 2011, e25155.
Schrouff, J., Perlbarg, V., Boly, M., et al. Brain functional integration decreases during propofol-induced loss of consciousness. NeuroImage 57 (2011), 198–205.
Liu, X., Lauer, K.K., Ward, B.D., Rao, S.M., Li, S.J., Hudetz, A.G., Propofol disrupts functional interactions between sensory and high-order processing of auditory verbal memory. Hum Brain Mapp 33 (2012), 2487–2498.
Boly, M., Moran, R., Murphy, M., et al. Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness. J Neurosci 32 (2012), 7082–7090.
Maksimow, A., Silfverhuth, M., Langsjo, J., et al. Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol. PLoS One, 9, 2014, e113616.
Raz, A., Grady, S.M., Krause, B.M., Uhlrich, D.J., Manning, K.A., Banks, M.I., Preferential effect of isoflurane on top–down vs. bottom–up pathways in sensory cortex. Front Syst Neurosci, 8, 2014, 191.
Nelson, L.E., Guo, T.Z., Lu, J., Saper, C.B., Franks, N.P., Maze, M., The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 5 (2002), 979–984.
Angel, A., The G. L. Brown lecture. Adventures in anaesthesia. Exp Physiol 76 (1991), 1–38.
Hubel, D.H., Wiesel, T.N., Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol 160 (1962), 106–154.
Hubel, D.H., Wiesel, T.N., Receptive fields and functional architecture of monkey striate cortex. J Physiol 195 (1968), 215–243.
Bastos, A.M., Usrey, W.M., Adams, R.A., Mangun, G.R., Fries, P., Friston, K.J., Canonical microcircuits for predictive coding. Neuron 76 (2012), 695–711.
Arnal, L.H., Giraud, A.L., Cortical oscillations and sensory predictions. Trends Cogn Sci 16 (2012), 390–398.
Chen, C.C., Kiebel, S.J., Kilner, J.M., et al. A dynamic causal model for evoked and induced responses. Neuroimage 59 (2012), 340–348.
Dentico, D., Cheung, B.L., Chang, J.Y., et al. Reversal of cortical information flow during visual imagery as compared to visual perception. Neuroimage 100 (2014), 237–243.
Ganis, G., Schendan, H.E., Visual mental imagery and perception produce opposite adaptation effects on early brain potentials. Neuroimage 42 (2008), 1714–1727.
Hipp, J.F., Hawellek, D.J., Corbetta, M., Siegel, M., Engel, A.K., Large-scale cortical correlation structure of spontaneous oscillatory activity. Nat Neurosci 15 (2012), 884–890.
Blain-Moraes, S., Tarnal, V., Vanini, G., et al. Neurophysiological correlates of sevoflurane-induced unconsciousness. Anesthesiology 122 (2015), 307–316.
Canolty, R.T., Knight, R.T., The functional role of cross-frequency coupling. Trends Cogn Sci 14 (2010), 506–515.
Chen, C.C., Kiebel, S.J., Friston, K.J., Dynamic causal modelling of induced responses. Neuroimage 41 (2008), 1293–1312.
Ramsay, M.A., Savege, T.M., Simpson, B.R., Goodwin, R., Controlled sedation with alphaxalone–alphadolone. BMJ 2 (1974), 656–659.
Murphy, M., Bruno, M.A., Riedner, B.A., et al. Propofol anesthesia and sleep: a high-density EEG study. Sleep 34 (2011), 283–291.
Marsh, B., White, M., Morton, N., Kenny, G.N., Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 67 (1991), 41–48.
Gosseries, O., Sarasso, S., Casarotto, S., et al. On the cerebral origin of EEG responses to TMS: insights from severe cortical lesions. Brain Stimul 8 (2015), 142–149.
Litvak, V., Mattout, J., Kiebel, S., et al. EEG and MEG data analysis in SPM8. Comput Intell Neurosci, 2011, 2011, 852961.
Felleman, D.J., Van Essen, D.C., Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1 (1991), 1–47.
David, O., Kiebel, S.J., Harrison, L.M., Mattout, J., Kilner, J.M., Friston, K.J., Dynamic causal modeling of evoked responses in EEG and MEG. Neuroimage 30 (2006), 1255–1272.
Kiebel, S.J., Garrido, M.I., Moran, R.J., Friston, K.J., Dynamic causal modelling for EEG and MEG. Cogn Neurodyn 2 (2008), 121–136.
Rosanova, M., Casali, A., Bellina, V., Resta, F., Mariotti, M., Massimini, M., Natural frequencies of human corticothalamic circuits. J Neurosci 29 (2009), 7679–7685.
Kass, R.E., Raftery, A.E., Bayes factors. J Am Stat Assoc 90 (1995), 773–795.
Lee, U., Muller, M., Noh, G.J., Choi, B., Mashour, G.A., Dissociable network properties of anesthetic state transitions. Anesthesiology 114 (2011), 872–881.
Bastos, A.M., Litvak, V., Moran, R., Bosman, C.A., Fries, P., Friston, K.J., A DCM study of spectral asymmetries in feedforward and feedback connections between visual areas V1 and V4 in the monkey. Neuroimage 108 (2015), 460–475.
Leslie, K., Sleigh, J., Paech, M.J., Voss, L., Lim, C.W., Sleigh, C., Dreaming and electroencephalographic changes during anesthesia maintained with propofol or desflurane. Anesthesiology 111 (2009), 547–555.
Boly, M., Garrido, M.I., Gosseries, O., et al. Preserved feedforward but impaired top-down processes in the vegetative state. Science 332 (2011), 858–862.
Bastos, A.M., Schoffelen, J.M., A Tutorial review of functional connectivity analysis methods and their interpretational pitfalls. Front Syst Neurosci, 9, 2015, 175.
Daunizeau, J., David, O., Stephan, K.E., Dynamic causal modelling: a critical review of the biophysical and statistical foundations. Neuroimage 58 (2011), 312–322.
Friston, K., Daunizeau, J., Stephan, K.E., Model selection and gobbledygook: response to Lohmann et al. Neuroimage 75 (2013), 275–278 discussion 9–81.
Pinotsis, D.A., Moran, R.J., Friston, K.J., Dynamic causal modeling with neural fields. Neuroimage 59 (2012), 1261–1274.
Fontolan, L., Morillon, B., Liegeois-Chauvel, C., Giraud, A.L., The contribution of frequency-specific activity to hierarchical information processing in the human auditory cortex. Nat Commun, 5, 2014, 4694.
Alkire, M.T., Hudetz, A.G., Tononi, G., Consciousness and anesthesia. Science 322 (2008), 876–880.
Bastos, A.M., Vezoli, J., Bosman, C.A., et al. Visual areas exert feedforward and feedback influences through distinct frequency channels. Neuron 85 (2015), 390–401.
Boveroux, P., Vanhaudenhuyse, A., Bruno, M.A., et al. Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 113 (2010), 1038–1053.
Lee, U., Mashour, G.A., Kim, S., Noh, G.J., Choi, B.M., Propofol induction reduces the capacity for neural information integration: implications for the mechanism of consciousness and general anesthesia. Conscious Cogn 18 (2009), 56–64.
Furl, N., Coppola, R., Averbeck, B.B., Weinberger, D.R., Cross-frequency power coupling between hierarchically organized face-selective areas. Cereb Cortex 24 (2014), 2409–2420.
Li, D., Li, X., Hagihira, S., Sleigh, J.W., Cross-frequency coupling during isoflurane anaesthesia as revealed by electroencephalographic harmonic wavelet bicoherence. Br J Anaesth 110 (2013), 409–419.
Mukamel, E.A., Pirondini, E., Babadi, B., et al. A transition in brain state during propofol-induced unconsciousness. J Neurosci 34 (2014), 839–845.
Johansen, J.W., Sebel, P.S., Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 93 (2000), 1336–1344.
Sanders, R.D., Raz, A., Banks, M.I., Boly, M., Tononi, G., Is consciousness fragile?. Br J Anaesth 116 (2016), 1–3.
Gaskell, A.L., Hight, D.F., Winders, J., et al. Frontal alpha–delta EEG does not preclude volitional response during anaesthesia: prospective cohort study of the isolated forearm technique. Br J Anaesth 119 (2017), 664–673.