title: Changes in cerebral metabolism in patients with a minimally conscious state responding to zolpidem.
abstract: BACKGROUND
  Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS).
  
  
  METHODS
  [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8).
  
  
  RESULTS
  Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration.
  
  
  CONCLUSIONS
  Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS.
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium ; Neurorehabilitation Lab, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School Boston, MA, USA.
authors.forename: Camille
authors.initials: C
authors.lastname: Chatelle
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium.
authors.forename: Aurore
authors.initials: A
authors.lastname: Thibaut
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium ; Center for Sleep and Consciousness, and Postle Laboratory, Department of Psychiatry, University of Wisconsin Madison, WI, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gosseries
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium.
authors.forename: Marie-Aurélie
authors.initials: MA
authors.lastname: Bruno
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium.
authors.forename: Athena
authors.initials: A
authors.lastname: Demertzi
authors.affiliation: Nuclear Medicine Department, University Hospital of Liège Liège, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Bernard
authors.affiliation: Nuclear Medicine Department, University Hospital of Liège Liège, Belgium.
authors.forename: Roland
authors.initials: R
authors.lastname: Hustinx
authors.affiliation: Department of Neuroradiology, University Hospital of Liège Liège, Belgium.
authors.forename: Luaba
authors.initials: L
authors.lastname: Tshibanda
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Bahri
authors.affiliation: Coma Science Group, Cyclotron Research Centre, University and University Hospital of Liège Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
keywords: brain metabolism; mesocircuit hypothesis; minimally conscious state; positron emission tomography; prefrontal cortex; zolpidem