title: Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.
abstract: BACKGROUND
  Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects.
  
  
  METHODS
  Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models.
  
  
  RESULTS
  Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia.
  
  
  CONCLUSIONS
  Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder.
  
  
  BACKGROUND
  NCT00504894.
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA Department of Anesthesia and Critical Care, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA kap9009@med.cornell.edu.
authors.forename: K O
authors.initials: KO
authors.lastname: Pryor
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA Department of Anesthesia and Critical Care, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Root
authors.affiliation: Department of Anesthesia and Critical Care, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: E
authors.initials: E
authors.lastname: Stern
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Anesthesia and Critical Care, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Veselis
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Silbersweig
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D004644:Emotions / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008568:Memory / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D015742:Propofol / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D010100:Oxygen; D015742:Propofol
keywords: amnesia, chemically induced; amygdala; fMRI; hippocampus; memory, drug effects; propofol, pharmacology