Predicting Drug-induced Memory and Sedation Changes Using Auditory Event-related Potentials. Veselis et al. (page 896)

Building on the work of researchers who have used specific components of event-related potentials (ERPs) to discriminate between the memory and sedative effects of drugs such as lorazepam and scopolamine, Veselis et al.  present a new analysis of memory effects using ERPs obtained in a previous study. That placebo-controlled study used 65 healthy volunteers who randomly received intravenously placebo, midazolam, propofol, thiopental, fentanyl with ondansetron, or ondansetron alone in five different stable target concentrations. The concentrations (three increasing, two decreasing) were achieved using a computer-controlled infusion pump to produce mild, moderate, and maximal sedation levels without loss of consciousness. At each target concentration, volunteers were given a list of 16 words to learn. In addition, ERPs were recorded while participants were asked to give a button-press response to a deviant auditory stimulus (target tone, standard oddball paradigm, 80:20 ratio, to elicit a P3 response). Then the researchers determined the predictive probabilities of various ERP components for memory (recognition of the words at the end of the day) and sedation (log reaction time to the deviant stimulus).

Results showed that the N2 latency of the ERP consistently predicted log reaction time in all groups. The N2P3 amplitude of the ERP was most predictive of memory performance for subjects to whom midazolam, propofol, and thiopental were administered. Midazolam and propofol affect memory differentially from their sedative effects, as indexed by specific components of the auditory ERP. Relating electrophysiologic changes to the memory and sedative effects of drugs allows researchers to independently measure these effects without the confounding subjective perceptions of the participants. These changes can then be related to brain images from positron emission tomography or magnetic resonance imaging to more accurately localize and quantify the neuroanatomic regions mediating these drug effects.