[en] Differentiation of the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS) is a persistent clinical challenge [1]. Based on positron emission tomography (PET) studies with [18F]-fluorodeoxyglucose (FDG) during sleep and anesthesia, the global cerebral metabolic rate of glucose has been proposed as an indicator of consciousness [2, 3]. Likewise, FDG-PET may contribute to the clinical diagnosis of disorders of consciousness (DOCs) [4, 5]. However, current methods are non-quantitative and have important drawbacks deriving from visually guided assessment of relative changes in brain metabolism [4]. We here used FDG-PET to measure resting state brain glucose metabolism in 131 DOC patients to identify objective quantitative metabolic indicators and predictors of awareness. Quantitation of images was performed by normalizing to extracerebral tissue. We show that 42% of normal cortical activity represents the minimal energetic requirement for the presence of conscious awareness. Overall, the cerebral metabolic rate accounted for the current level, or imminent return, of awareness in 94% of the patient population, suggesting a global energetic threshold effect, associated with the reemergence of consciousness after brain injury. Our data further revealed that regional variations relative to the global resting metabolic level reflect preservation of specific cognitive or sensory modules, such as vision and language comprehension. These findings provide a simple and objective metabolic marker of consciousness, which can readily be implemented clinically. The direct correlation between brain metabolism and behavior further suggests that DOCs can fundamentally be understood as pathological neuroenergetic conditions and provide a unifying physiological basis for these syndromes.
Disciplines :
Neurology
Author, co-author :
Stender, Johan; BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, Copenhagen, Denmark, Cyclotron Research Center and Department of Neurology, CHU Sart Tilman, University of Liège, Avenue de l'hôpital 11, Liège, Belgium
Mortensen, Kristian Nygaard; BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, Copenhagen, Denmark
Thibaut, Aurore ; Université de Liège - ULiège > GIGA Consciousness: Coma Science Group
Darkner, Sune; Department of Computer Science, University of Copenhagen, Universitetsparken 5, Copenhagen, Denmark
Laureys, Steven ; Université de Liège - ULiège > GIGA Consciousness: Coma Science Group
Gjedde, Albert; BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, Copenhagen, Denmark
Kupers, Ron; BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, Copenhagen, Denmark, Department of Radiology & Biomedical Imaging, Yale University, 300 Cedar Street, New Haven, CT, United States
Language :
English
Title :
The Minimal Energetic Requirement of Sustained Awareness after Brain Injury
Publication date :
2016
Journal title :
Current Biology
ISSN :
0960-9822
eISSN :
1879-0445
Publisher :
Cell Press
Volume :
26
Issue :
11
Pages :
1494-1499
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
University of Copenhage F.R.S.-FNRS - Fonds de la Recherche Scientifique JSMF - James S McDonnell Foundation BAEF - Belgian American Educational Foundation WBI - Wallonie-Bruxelles International FEDER - Fonds Européen de Développement Régional ASE - Agence Spatiale Européenne the Wallonia-Brussels Federation Concerted Research Action Belgian interuniversity attraction pole
1 Laureys, S., Schiff, N.D., Coma and consciousness: paradigms (re)framed by neuroimaging. Neuroimage 61 (2012), 478–491.
2 Shulman, R.G., Hyder, F., Rothman, D.L., Baseline brain energy supports the state of consciousness. Proc. Natl. Acad. Sci. USA 106 (2009), 11096–11101.
3 Alkire, M.T., Quantitative EEG correlations with brain glucose metabolic rate during anesthesia in volunteers. Anesthesiology 89 (1998), 323–333.
4 Stender, J., Gosseries, O., Bruno, M.-A., Charland-Verville, V., Vanhaudenhuyse, A., Demertzi, A., Chatelle, C., Thonnard, M., Thibaut, A., Heine, L., et al. Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study. Lancet 384 (2014), 514–522.
5 Laureys, S., Owen, A.M., Schiff, N.D., Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 3 (2004), 537–546.
6 Stender, J., Kupers, R., Rodell, A., Thibaut, A., Chatelle, C., Bruno, M.-A., Gejl, M., Bernard, C., Hustinx, R., Laureys, S., Gjedde, A., Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients. J. Cereb. Blood Flow Metab. 35 (2015), 58–65.
7 Bruno, M.-A., Majerus, S., Boly, M., Vanhaudenhuyse, A., Schnakers, C., Gosseries, O., Boveroux, P., Kirsch, M., Demertzi, A., Bernard, C., et al. Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients. J. Neurol. 259 (2012), 1087–1098.
8 Bruno, M.-A., Vanhaudenhuyse, A., Schnakers, C., Boly, M., Gosseries, O., Demertzi, A., Majerus, S., Moonen, G., Hustinx, R., Laureys, S., Visual fixation in the vegetative state: an observational case series PET study. BMC Neurol., 10, 2010, 35.
9 Shulman, R.G., Rothman, D.L., Hyder, F., Stimulated changes in localized cerebral energy consumption under anesthesia. Proc. Natl. Acad. Sci. USA 96 (1999), 3245–3250.
10 Lin, J.H., Divergence measures based on the Shannon entropy. IEEE Trans. Inf. Theory 37 (1991), 145–151.
11 Bruno, M.A., Fernández-Espejo, D., Lehembre, R., Tshibanda, L., Vanhaudenhuyse, A., Gosseries, O., Lommers, E., Napolitani, M., Noirhomme, Q., Boly, M., et al. Multimodal neuroimaging in patients with disorders of consciousness showing “functional hemispherectomy”. Prog. Brain Res. 193 (2011), 323–333.
12 Carson, B.S., Javedan, S.P., Freeman, J.M., Vining, E.P., Zuckerberg, A.L., Lauer, J.A., Guarnieri, M., Hemispherectomy: a hemidecortication approach and review of 52 cases. J. Neurosurg. 84 (1996), 903–911.
13 Gazzaniga, M.S., Forty-five years of split-brain research and still going strong. Nat. Rev. Neurosci. 6 (2005), 653–659.
14 Gjedde, A., Bauer, W.R., Wong, D., Neurokinetics. Gjedde, A., Bauer, W.R., Wong, D., (eds.) The Dynamics of Neurobiology In Vivo, 2011, Springer Verlag, 241–290.
15 Kuzawa, C.W., Chugani, H.T., Grossman, L.I., Lipovich, L., Muzik, O., Hof, P.R., Wildman, D.E., Sherwood, C.C., Leonard, W.R., Lange, N., Metabolic costs and evolutionary implications of human brain development. Proc. Natl. Acad. Sci. USA 111 (2014), 13010–13015.
16 Cunnane, S., Nugent, S., Roy, M., Courchesne-Loyer, A., Croteau, E., Tremblay, S., Castellano, A., Pifferi, F., Bocti, C., Paquet, N., et al. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition 27 (2011), 3–20.
17 Fridman, E.A., Beattie, B.J., Broft, A., Laureys, S., Schiff, N.D., Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain. Proc. Natl. Acad. Sci. USA 111 (2014), 6473–6478.
18 White, N.S., Alkire, M.T., Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness. Neuroimage 19 (2003), 402–411.
19 Schiff, N.D., Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci. 33 (2010), 1–9.
