Multivariate analysis of single-sweep evoked brain potentials for pharmaco-electroencephalography

Current findings on altered evoked potentials (EPs) caused by morphine are based on common alterations for a group of subjects after drug administration. However, this ignores the analysis of individual responses, which may explain the clinical differences in efficacy. Therefore, we explored the individual responses to morphine in terms of the altered single-sweep characteristics in a placebo-controlled crossover study. To account for multifactorial mechanisms, several characteristics were assessed simultaneously by multivariate pattern analysis (MVPA).

EPs were recorded from 62 channels and obtained before and after morphine and placebo administration during repeated electrical stimulations of the oesophagus in 12 healthy males. Additionally, the pain detection threshold was recorded to reflect the subjective analgesic effect in each subject. The characteristics of the sweeps were extracted by a multivariate matching pursuit algorithm with Gabor atoms implemented with a variable amplitude and constant phase across the sweeps. The single-sweep amplitudes were used as input to an MVPA algorithm to discriminate individual responses. The accuracy of the MVPA for each individual subject was used for correlation analysis of the analgesic effect.

The mean classification accuracy when discriminating pre- and posttreatment morphine responses was 72% (p = 0.01). The individual classification accuracy was positively correlated to the analgesic effect of morphine (p = 0.03). Furthermore, the 2 posttreatment responses were classified and validated by the classification of the 2 pretreatment responses (p = 0.001).

The alterations in the single-sweep EPs after morphine reflect the analgesic effect. The MVPA approach is a novel methodology for monitoring the individual efficacy of analgesics.