[en] In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness.
Disciplines :
Neurology Neurosciences & behavior Radiology, nuclear medicine & imaging
Abulafia R, Zalkind V, Devor M. 2009. Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital. J Neurosci 29:7053-7064.
Alkire M.T., McReynolds J.R., Hahn E.L., Trivedi AN. 2007. Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Anesthesiology 107:264-272.
Angeles Fernandez-Gil M, Palacios-Bote R, Leo-Barahona M, Mora-Encinas JP. 2010. Anatomy of the brainstem: a gaze into the stem of life. Semin Ultrasound CT MR 31:196-219.
Aron A.R., Robbins T.W., Poldrack RA. 2004. Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8:170-177.
Beckmann C.F., DeLuca M, Devlin J.T., Smith SM. 2005. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci 360:1001-1013.
Ben-Simon E, Podlipsky I, Okon-Singer H, Gruberger M, Cvetkovic D, Intrator N, Hendler T. 2013. The dark side of the alpha rhythm: fMRI evidence for induced alpha modulation during complete darkness. Eur J Neurosci 37:795-803.
Birn R.M., Diamond J.B., Smith M.A., Bandettini PA. 2006. Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. Neuroimage 31:1536-1548.
Boly M, Moran R, Murphy M, Boveroux P, Bruno M.A., Noirhomme Q, Ledoux D, Bonhomme V, Brichant J.F., Tononi G, Laureys S, Friston K. 2012. Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness. J Neurosci 32:7082-7090.
Boly M, Tshibanda L, Vanhaudenhuyse A, Noirhomme Q, Schnakers C, Ledoux D, Boveroux P, Garweg C, Lambermont B, Phillips C, Luxen A, Moonen G, Bassetti C, Maquet P, Laureys S. 2009. Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Hum Brain Mapp 30:2393-2400.
Bonnelle V, Ham T.E., Leech R, Kinnunen K.M., Mehta M.A., Greenwood R.J., Sharp DJ. 2012. Salience network integrity predicts default mode network function after traumatic brain injury. Proc Natl Acad Sci U S A 109:4690-4695.
Boveroux P, Vanhaudenhuyse A, Bruno M.A., Noirhomme Q, Lauwick S, Luxen A, Degueldre C, Plenevaux A, Schnakers C, Phillips C, Brichant J.F., Bonhomme V, Maquet P, Greicius M.D., Laureys S, Boly M. 2010. Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 113:1038-1053.
Brown E.N., Lydic R, Schiff ND. 2010. General anesthesia, sleep, and coma. N Engl J Med 363:2638-2650.
Brown E.N., Purdon P.L., Van Dort CJ. 2011. General anesthesia and altered states of arousal: a systems neuroscience analysis. Annu Rev Neurosci 34:601-628.
Ching S, Cimenser A, Purdon P.L., Brown E.N., Kopell NJ. 2010. Thalamocortical model for a propofol-induced alpha-rhythm associated with loss of consciousness. Proc Natl Acad Sci U S A 107:22665-22670.
Cimenser A, Purdon P.L., Pierce E.T., Walsh J.L., Salazar-Gomez A.F., Harrell P.G., Tavares-Stoeckel C, Habeeb K, Brown EN. 2011. Tracking brain states under general anesthesia by using global coherence analysis. Proc Natl Acad Sci U S A 108:8832-8837.
Constantinople C.M., Bruno RM. 2011 Effects and mechanisms of wakefulness on local cortical networks. Neuron 69:1061-1068.
Corfield D.R., Murphy K, Josephs O, Adams L, Turner R. 2001. Does hypercapnia-induced cerebral vasodilation modulate the hemodynamic response to neural activation? Neuroimage 13:1207-1211.
Damoiseaux J.S., Rombouts S.A., Barkhof F, Scheltens P, Stam C.J., Smith S.M., Beckmann CF. 2006. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A 103:13848-13853.
de Lecea L, Carter M.E., Adamantidis A. 2012. Shining light on wakefulness and arousal. Biol Psychiatry 71:1046-1052.
De Martino F, Gentile F, Esposito F, Balsi M, Di Salle F, Goebel R, Formisano E. 2007. Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers. NeuroImage 34:177-194.
Demertzi A, Soddu A, Faymonville M.E., Bahri M.A., Gosseries O, Vanhaudenhuyse A, Phillips C, Maquet P, Noirhomme Q, Luxen A, Laureys S. 2011. Hypnotic modulation of resting state fMRI default mode and extrinsic network connectivity. Prog Brain Res 193:309-322.
Devor M, Zalkind V. 2001. Reversible analgesia, atonia, and loss of consciousness on bilateral intracerebral microinjection of pentobarbital. Pain 94:101-112.
Duann J.R., Ide J.S., Luo X, Li CS. 2009. Functional connectivity delineates distinct roles of the inferior frontal cortex and presupplementary motor area in stop signal inhibition. J Neurosci 29:10171-10179.
Ellison-Wright I, Bullmore E. 2010. Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr Res 117:1-12.
Fair D.A., Cohen A.L., Dosenbach N.U., Church J.A., Miezin F.M., Barch D.M., Raichle M.E., Petersen S.E., Schlaggar BL. 2008. The maturing architecture of the brain's default network. Proc Natl Acad Sci U S A 105:4028-4032.
Fiset P, Paus T, Daloze T, Plourde G, Meuret P, Bonhomme V, Hajj-Ali N, Backman S.B., Evans AC. 1999. Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study. J Neurosci 19:5506-5513.
Fox M.D., Snyder A.Z., Vincent J.L., Corbetta M, Van Essen D.C., Raichle ME. 2005. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:9673-9678.
Foxe J.J., Snyder AC. 2011. The role of alpha-band brain oscillations as a sensory suppression mechanism during selective attention. Front Psychol 2:154.
Giacino J, Fins J.J., Machado A, Schiff ND. 2012. Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities. Neuromodulation 15:339-349.
Greicius M.D., Kiviniemi V, Tervonen O, Vainionpaa V, Alahuhta S, Reiss A.L., Menon V. 2008. Persistent default-mode network connectivity during light sedation. Hum Brain Mapp 29:839-847.
Guldenmund P, Vanhaudenhuyse A, Boly M, Laureys S, Soddu A. 2012. A default mode of brain function in altered states of consciousness. Arch Ital Biol 150:107-121.
Hanslmayr S, Gross J, Klimesch W, Shapiro KL. 2011. The role of alpha oscillations in temporal attention. Brain Res Rev 67:331-343.
Horovitz S.G., Braun A.R., Carr W.S., Picchioni D, Balkin T.J., Fukunaga M, Duyn JH. 2009. Decoupling of the brain's default mode network during deep sleep. Proc Natl Acad Sci U S A 106:11376-11381.
Hyvarinen A, Karhunen J, Oja E. 2001. Independent Component Analysis. John Wiley & Sons.
Jensen O, Mazaheri A. 2010. Shaping functional architecture by oscillatory alpha activity: gating by inhibition. Front Hum Neurosci 4:186.
Lachaux J.P., Fonlupt P, Kahane P, Minotti L, Hoffmann D, Bertrand O, Baciu M. 2007. Relationship between task-related gamma oscillations and BOLD signal: new insights from combined fMRI and intracranial EEG. Hum Brain Mapp 28:1368-1375.
Laureys S, Boly M. 2008. The changing spectrum of coma. Nat Clin Pract Neurol 4:544-546.
Lieberman M.D., Cunningham WA. 2009. Type I and Type II error concerns in fMRI research: re-balancing the scale. Soc Cogn Affect Neurosci 4:423-428.
Linnman C, Moulton E.A., Barmettler G, Becerra L, Borsook D. 2012. Neuroimaging of the periaqueductal gray: state of the field. Neuroimage 60:505-522.
Martuzzi R, Ramani R, Qiu M, Rajeevan N, Constable RT. 2010. Functional connectivity and alterations in baseline brain state in humans. Neuroimage 49:823-834.
Mathewson K.E., Lleras A, Beck D.M., Fabiani M, Ro T, Gratton G. 2011. Pulsed out of awareness: EEG alpha oscillations represent a pulsed-inhibition of ongoing cortical processing. Front Psychol 2:99.
Maudoux A, Lefebvre P, Cabay J.E., Demertzi A, Vanhaudenhuyse A, Laureys S, Soddu A. 2012. Connectivity graph analysis of the auditory resting state network in tinnitus. Brain Res 1485:10-21.
McKeown M.J., Makeig S, Brown G.G., Jung T.P., Kindermann S.S., Bell A.J., Sejnowski TJ. 1998. Analysis of fMRI data by blind separation into independent spatial components. Hum Brain Mapp 6:160-188.
Menon V, Uddin LQ. 2010. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 214:655-667.
Modinos G, Ormel J, Aleman A. 2009. Activation of anterior insula during self-reflection. PLoS One 4:e4618.
Murphy M, Bruno M.A., Riedner B.A., Boveroux P, Noirhomme Q, Landsness E.C., Brichant J.F., Phillips C, Massimini M, Laureys S, Tononi G, Boly M. 2011. Propofol anesthesia and sleep: a high-density EEG study. Sleep 34:283-291A.
Olson D.M., Thoyre S.M., Auyong DB. 2007. Perspectives on sedation assessment in critical care. AACN Adv Crit Care 18:380-395.
Palaniyappan L, Liddle PF. 2012. Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. J Psychiatry Neurosci 37:17-27.
Parvizi J, Damasio A. 2001. Consciousness and the brainstem. Cognition 79:135-160.
Pinault D. 2011. Dysfunctional thalamus-related networks in schizophrenia. Schizophr Bull 37:238-243.
Saper C.B., Cano G, Scammell TE. 2005. Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol 493:92-98.
Schiff ND. 2008. Central thalamic contributions to arousal regulation and neurological disorders of consciousness. Ann N Y Acad Sci 1129:105-118.
Schiff N.D., Fins JJ. 2007. Deep brain stimulation and cognition: moving from animal to patient. Curr Opin Neurol 20:638-642.
Schiff N.D., Plum F. 2000. The role of arousal and “gating” systems in the neurology of impaired consciousness. J Clin Neurophysiol 17:438-452.
Schrouff J, Perlbarg V, Boly M, Marrelec G, Boveroux P, Vanhaudenhuyse A, Bruno M.A., Laureys S, Phillips C, Pelegrini-Issac M, Maquet P, Benali H. 2011. Brain functional integration decreases during propofol-induced loss of consciousness. Neuroimage 57:198-205.
Seeley WW. 2008. Selective functional, regional, and neuronal vulnerability in frontotemporal dementia. Curr Opin Neurol 21:701-707.
Seeley WW. 2010. Anterior insula degeneration in frontotemporal dementia. Brain Struct Funct 214:465-475.
Shah S.A., Schiff ND. 2010. Central thalamic deep brain stimulation for cognitive neuromodulationâa review of proposed mechanisms and investigational studies. Eur J Neurosci 32:1135-1144.
Soddu A, Vanhaudenhuyse A, Bahri M.A., Bruno M.A., Boly M, Demertzi A, Tshibanda J.F., Phillips C, Stanziano M, Ovadia-Caro S, Nir Y, Maquet P, Papa M, Malach R, Laureys S, Noirhomme Q. 2012. Identifying the default-mode component in spatial IC analyses of patients with disorders of consciousness. Hum Brain Mapp 33:778-796.
Tang L, Ge Y, Sodickson D.K., Miles L, Zhou Y, Reaume J, Grossman RI. 2011. Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury. Radiology 260:831-840.
Vanhaudenhuyse A, Demertzi A, Schabus M, Noirhomme Q, Bredart S, Boly M, Phillips C, Soddu A, Luxen A, Moonen G, Laureys S. 2011. Two distinct neuronal networks mediate the awareness of environment and of self. J Cogn Neurosci 23:570-578.
Vanhaudenhuyse A, Noirhomme Q, Tshibanda L.J., Bruno M.A., Boveroux P, Schnakers C, Soddu A, Perlbarg V, Ledoux D, Brichant J.F., Moonen G, Maquet P, Greicius M.D., Laureys S, Boly M. 2009. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 133:161-171.
Wang D.S., Orser BA. 2011. Inhibition of learning and memory by general anesthetics. Can J Anaesth 58:167-177.
Wise R.G., Ide K, Poulin M.J., Tracey I. 2004. Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal. Neuroimage 21:1652-1664.
Xie G, Deschamps A, Backman S.B., Fiset P, Chartrand D, Dagher A, Plourde G. 2011. Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study. Br J Anaesth 106:548-557.
