A cognitive and neurophysiological test of change from an individual's baseline

Abstract

Objective: An automated cognitive neurophysiological test is presented that characterizes how an individual was affected by a drug or treatment. The test calculates sub-scores for working memory task performance, cortical activation, and alertness, and combines the sub-scores into an overall score.

Methods: The test was applied in a double-blind, placebo-controlled study of alcohol, caffeine, diphenhydramine, and sleep deprivation in 16 healthy adults.

Results: The between- and within-day variability of the sub-scores and overall scores for placebo were all near zero, suggesting that the scores are stable. All treatments affected the overall score, while differential effects on sub-scores highlighted the added value of EEG measures.

Conclusions: The test is sensitive to relatively mild alterations in cognitive function. Its automation makes it suitable for use in large-scale clinical trials.

Significance: By combining task performance with EEG brain function measures, the test may prove to have better sensitivity and specificity in detecting changes due to drugs or other treatments than comparable neuropsychological test batteries that do not directly measure brain function signals.

Fig. 1

As the working memory task gets more difficult, EEG frontal theta power increases and parietal alpha power decreases. (Left): 4–14Hz EEG power at frontal (Fz) and parietal (Pz) midline sites measured during an easier (low load -- light line) and more difficult (high load -- dark line) n-back WM task from 80 participants (adapted from Gevins and Smith, 2000). (Right): 120-electrode WM task EEG images for a single participant, mapped onto a cortical model derived from the participant’s MRI (adapted from Gevins et al., 1996). Although such dense electrode arrays improve topographic mapping, practical cognitive neuromonitoring can be accomplished with far fewer electrodes.

Fig. 2

EEG power spectra from the midline parietal-occipital electrode recorded from 16 healthy adults in resting eyes closed (left) and eyes open (right) conditions, 1.5 hours after administration of alcohol (dotted line), placebo (dark solid line), or caffeine (light solid line). Across both resting conditions, low frequency EEG power in the delta-theta band was larger after alcohol but smaller after caffeine. The ratio of alpha power in the eyes-closed to eyes-open conditions was smaller after alcohol but larger after caffeine. Such changes contributed to the alertness sub-score decreasing after alcohol (p<.05) but increasing after caffeine (p<.01).