title: Dexmedetomidine Disrupts the Local and Global Efficiencies of Large-scale Brain Networks.
abstract: BACKGROUND
  A clear understanding of the neural basis of consciousness is fundamental to research in clinical and basic neuroscience disciplines and anesthesia. Recently, decreased efficiency of information integration was suggested as a core network feature of propofol-induced unconsciousness. However, it is unclear whether this finding can be generalized to dexmedetomidine, which has a different molecular target.
  
  
  METHODS
  Dexmedetomidine was administered as a 1-μg/kg bolus over 10 min, followed by a 0.7-μg · kg · h infusion to healthy human volunteers (age range, 18 to 36 yr; n = 15). Resting-state functional magnetic resonance imaging data were acquired during baseline, dexmedetomidine-induced altered arousal, and recovery states. Zero-lag correlations between resting-state functional magnetic resonance imaging signals extracted from 131 brain parcellations were used to construct weighted brain networks. Network efficiency, degree distribution, and node strength were computed using graph analysis. Parcellated brain regions were also mapped to known resting-state networks to study functional connectivity changes.
  
  
  RESULTS
  Dexmedetomidine significantly reduced the local and global efficiencies of graph theory-derived networks. Dexmedetomidine also reduced the average brain connectivity strength without impairing the degree distribution. Functional connectivity within and between all resting-state networks was modulated by dexmedetomidine.
  
  
  CONCLUSIONS
  Dexmedetomidine is associated with a significant drop in the capacity for efficient information transmission at both the local and global levels. These changes result from reductions in the strength of connectivity and also manifest as reduced within and between resting-state network connectivity. These findings strengthen the hypothesis that conscious processing relies on an efficient system of information transfer in the brain.
authors.affiliation: From the Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada (J.A.H.); Department of Radiology, Martinos Center for Biomedical Imaging (M.L.L., J.K., V.N.), Department of Neurology (S.K.), and Department of Anesthesia, Critical Care and Pain Medicine (L.G., E.N.B., O.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; Clinical Research Division, Korea Institute for Oriental Medicine, Daejeon, Korea (J.K.); and Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts (E.N.B.).
authors.forename: Javeria A
authors.initials: JA
authors.lastname: Hashmi
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.forename: Sheraz
authors.initials: S
authors.lastname: Khan
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping / Q000379:methods*; D020927:Dexmedetomidine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects; D014474:Unconsciousness / Q000139:chemically induced; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine