Tracking the cognitive pharmacodynamics of psychoactive substances with combinations of behavioral and...

Many common pharmacological treatments have effects on cognitive ability. Psychometric task batteries used to characterize such effects do not provide direct information about treatment-related changes in brain function. Since overt task performance reflects motivation and effort as well as ability, behavioral measures alone may overestimate or underestimate the impact of a pharmacological intervention on brain function. Here we present a method that combines behavioral and neurophysiological measures in an attempt to detect the psychoactive effects of pharmacological treatments with greater sensitivity than that provided by behavioral measures alone. Initial application of the method is made to the data from a double blind, placebo-controlled, crossover study in which caffeine, diphenhydramine, and alcohol were used to alter the mental state of 16 healthy subjects at rest and while they performed low load and high load versions of a working memory task. For each intervention, more sensitive detection of drug or alcohol effects over a four hour period was obtained when EEG variables were included in multivariate analyses than when only behavioral variables were used. These initial results suggest that it can be useful to incorporate neurophysiological measures of brain activity into inferences concerning the acute impact of drugs on mental function, and demonstrate the feasibility of using multivariate combinations of behavioral and neurophysiological measures to sensitively characterize the pharmacodynamics of drug-induced changes in cognition.