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.
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.
Pryor
Kane O
KO
Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA. kap9009@med.cornell.edu
Reinsel
Ruth A
RA
Mehta
Meghana
M
Li
Yuelin
Y
Wixted
John T
JT
Veselis
Robert A
RA
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
D018686:Anesthetics, Intravenous