title: The Minimal Energetic Requirement of Sustained Awareness after Brain Injury.
abstract: 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 [(18)F]-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.
authors.affiliation: BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, 2200 Copenhagen, Denmark; Cyclotron Research Center and Department of Neurology, CHU Sart Tilman, University of Liège, Avenue de l'hôpital 11, 4000 Liège, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Stender
authors.affiliation: BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, 2200 Copenhagen, Denmark.
authors.forename: Kristian Nygaard
authors.initials: KN
authors.lastname: Mortensen
authors.affiliation: Cyclotron Research Center and Department of Neurology, CHU Sart Tilman, University of Liège, Avenue de l'hôpital 11, 4000 Liège, Belgium.
authors.forename: Aurore
authors.initials: A
authors.lastname: Thibaut
authors.affiliation: Department of Computer Science, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark.
authors.forename: Sune
authors.initials: S
authors.lastname: Darkner
authors.affiliation: Cyclotron Research Center and Department of Neurology, CHU Sart Tilman, University of Liège, Avenue de l'hôpital 11, 4000 Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
authors.affiliation: BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, 2200 Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: BRAINlab, Department of Neuroscience & Pharmacology, Panum Institute, University of Copenhagen, Nørre Allé 10, 2200 Copenhagen, Denmark; Department of Radiology & Biomedical Imaging, Yale University, 300 Cedar Street, New Haven, CT 06520, USA. Electronic address: kupers@sund.ku.dk.
authors.forename: Ron
authors.initials: R
authors.lastname: Kupers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001364:Awareness; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000000981:diagnostic imaging*; D003244:Consciousness Disorders / Q000000981:diagnostic imaging*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018458:Persistent Vegetative State / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: FDG-PET; brain injury; consciousness; glucose metabolism; minimally conscious state; unresponsive wakefulness syndrome; vegetative state