Long-term and within-day variability of working memory performance and EEG in individuals.

OBJECTIVE: Assess individual-subject long-term and within-day variability of a combined behavioral and EEG test of working memory. METHODS: EEGs were recorded from 16 adults performing n-back working memory tasks, with 10 tested in morning and afternoon sessions over several years. Participants were also tested after ingesting non-prescription medications or recreational substances. Performance and EEG measures were analyzed to derive an Overall score and three constituent sub-scores characterizing changes in performance, cortical activation, and alertness from each individual's baseline. Long-term and within-day variability were determined for each score; medication effects were assessed by reference to each individual's normal day-to-day variability. RESULTS: Over the several year period, the mean Overall score and sub-scores were approximately zero with standard deviations less than one. Overall scores were lower and their variability higher in afternoon relative to morning sessions. At the group level, alcohol, diphenhydramine and marijuana produced significant effects, but there were large individual differences. CONCLUSIONS: Objective working memory measures incorporating performance and EEG are stable over time and sensitive at the level of individual subjects to interventions that affect neurocognitive function. SIGNIFICANCE: With further research these measures may be suitable for use in individualized medical care by providing a sensitive assessment of incipient illness and response to treatment.

Combined neuropsychological and neurophysiological assessment of drug effects on groups and individuals.

An initial standardized approach for combining neuropsychological and neurophysiological measures in order to assess the neurocognitive effects of drugs in groups and individuals is introduced. Its application is illustrated with sedatives, antiepileptic drugs, psychostimulants, antihistamines, and intoxicants. Task performance, electroencephalography, and evoked potential measures during computerized attention and memory testing that are most sensitive to drug effects are identified in a sample population and then applied to individuals. In six example exploratory studies, drug effects were detected with an average area under curve (AUC) of 0.97 (p < 0.0001; 95% sensitivity, 96% specificity). In 10 example validation studies with other drugs and/or different subjects and populations, detection was strong in the eight studies with drugs and doses known to have significant neurocognitive effects (AUC 0.83, p < 0.0001; 82% sensitivity, 89% specificity), whereas no effect was detected in the two studies with drugs known to have faint neurocognitive effects (AUC 0.56, p > 0.10). Individual differences in response to different drugs with similar clinical uses, to varying doses of the same drug, and in pharmacodynamic response were then demonstrated. The significant (p < 0.01) increase in sensitivity and specificity of combined neuropsychological and neurophysiological measures compared with the former alone suggests that fewer subjects may be needed to assess the neurocognitive effects of drugs in future studies. The findings suggest that the concept of combining neuropsychological testing with simultaneous measures of neurophysiological function is worth further exploration.