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

Anesthesiology. 2010 Aug;113(2):313-26. doi: 10.1097/ALN.0b013e3181dfd401.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amnesia / chemically induced
  • Amnesia / diagnosis
  • Amnesia / physiopathology*
  • Anesthetics, Intravenous / administration & dosage*
  • Arousal / drug effects
  • Arousal / physiology*
  • Electroencephalography / drug effects
  • Evoked Potentials, Visual / drug effects
  • Evoked Potentials, Visual / physiology*
  • Female
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Middle Aged
  • Parietal Lobe / drug effects
  • Parietal Lobe / physiology*
  • Predictive Value of Tests
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Reaction Time / drug effects
  • Reaction Time / physiology*
  • Young Adult


  • Anesthetics, Intravenous