title: Visual P2-N2 complex and arousal at the time of encoding predict the time domain characteristics of amnesia for multiple intravenous anesthetic drugs in humans.
abstract: BACKGROUND
  Intravenous anesthetics have marked effects on memory function, even at subclinical concentrations. Fundamental questions remain in characterizing anesthetic amnesia and identifying affected system-level processes. The authors applied a mathematical model to evaluate time-domain components of anesthetic amnesia in human subjects.
  
  
  METHODS
  Sixty-one volunteers were randomized to receive propofol (n = 12), thiopental (n = 13), midazolam (n = 12), dexmedetomidine (n = 12), or placebo (n = 12). With drug present, subjects encoded pictures into memory using a 375-item continuous recognition task, with subsequent recognition later probed with drug absent. Memory function was sampled at up to 163 time points and modeled over the time domain using a two-parameter, first-order negative power function. The parietal event-related P2-N2 complex was derived from electroencephalography, and arousal was repeatedly sampled. Each drug was evaluated at two concentrations.
  
  
  RESULTS
  The negative power function consistently described the course of amnesia (mean R = 0.854), but there were marked differences between drugs in the modulation of individual components (P < 0.0001). Initial memory strength was a function of arousal (P = 0.005), whereas subsequent decay was related to the reaction time (P < 0.0001) and the P2-N2 complex (P = 0.007/0.002 for discrete components).
  
  
  CONCLUSIONS
  In humans, the amnesia caused by multiple intravenous anesthetic drugs is characterized by arousal-related effects on initial trace strength, and a subsequent decay predicted by attenuation of the P2-N2 complex at encoding. The authors propose that the failure of normal memory consolidation follows drug-induced disruption of interregional synchrony critical for neuronal plasticity and discuss their findings in the framework of memory systems theory.
authors.affiliation: Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA. kap9009@med.cornell.edu
authors.forename: Kane O
authors.initials: KO
authors.lastname: Pryor
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Reinsel
authors.forename: Meghana
authors.initials: M
authors.lastname: Mehta
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Li
authors.forename: John T
authors.initials: JT
authors.lastname: Wixted
authors.forename: Robert A
authors.initials: RA
authors.lastname: Veselis
mesh_terms: D000293:Adolescent; D000328:Adult; D000647:Amnesia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D004569:Electroencephalography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D010296:Parietal Lobe / Q000187:drug effects / Q000502:physiology*; D011237:Predictive Value of Tests; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous