title: Critical involvement of the thalamus and precuneus during restoration of consciousness with physostigmine in humans during propofol anaesthesia: a positron emission tomography study.
abstract: BACKGROUND
  Functional brain imaging offers a way to investigate how general anaesthetics impair consciousness. However, functional imaging changes may result from drug effects unrelated to hypnosis. Establishing a causal link with loss of consciousness is thus difficult.
  
  
  METHODS
  To identify changes of neuronal activity functionally linked to the level of consciousness, physostigmine was used to restore consciousness without changing the anaesthetic concentration in 11 subjects anaesthetized with propofol. Eight subjects (responders) regained consciousness after physostigmine and three did not (non-responders). Positron emission tomography was used to measure regional cerebral blood flow (rCBF); during baseline (awake), after anaesthesia-induced loss of consciousness, after physostigmine administration, and recovery. In addition to subtraction analyses, we used conjunction analysis in the responders to identify changes common to the baseline-anaesthesia and physostigmine-anaesthesia contrasts.
  
  
  RESULTS
  Complete data were available for seven subjects (four responders and three non-responders). The analyses revealed that unconsciousness was associated with rCBF decreases in the thalamus and precuneus. Restoration of consciousness by physostigmine was associated with rCBF increases in these same structures, with the strongest effect in the thalamus.
  
  
  CONCLUSIONS
  The results provide strong evidence that reductions in rCBF in the thalamus and precuneus are functionally related to propofol-induced unconsciousness independently of any non-specific effects of propofol. These observations confirm that the thalamus and precuneus are key elements to understand how general anaesthetics cause unconsciousness and how patients wake up from anaesthesia. Furthermore, they are consistent with the notion that anaesthetic-induced unconsciousness is associated with reduced cholinergic activation.
authors.affiliation: Department of Anesthesia, McGill University, Montreal, QC, Canada H3A 1A2.
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.forename: A
authors.initials: A
authors.lastname: Deschamps
authors.forename: S B
authors.initials: SB
authors.lastname: Backman
authors.forename: P
authors.initials: P
authors.lastname: Fiset
authors.forename: D
authors.initials: D
authors.lastname: Chartrand
authors.forename: A
authors.initials: A
authors.lastname: Dagher
authors.forename: G
authors.initials: G
authors.lastname: Plourde
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects*; D010830:Physostigmine / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods; D015742:Propofol / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000187:drug effects*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D010830:Physostigmine; D015742:Propofol