Pre-stimulus/post-stimulus relations in EEG spectra and their modulations by an opioid and an antidepressant

Parametric spectral analysis of late cerebral potential components (later than 80 msec) evoked by painful somatosensory stimuli reveals a stimulus-induced increase of power in the low frequencies, delta and theta. This paper investigates the effect kinetics of the opioid meperidine (150 mg, p.o.) and the antidepressant imipramine (100 mg, p.o.) on spontaneous and evoked EEG activity in a placebo-controlled double-blind cross-over study with 20 healthy male subjects. Brief electrical stimuli (5 msec) were intracutaneously applied on the finger tip with randomized intensities above pain threshold and intervals between 10 and 20 sec. Spectra of short (500 msec) pre- and post-stimulus EEG epochs were evaluated using the maximum entropy method (model order 20). The main findings were: (1) The maximum effects of the 2 drugs upon spontaneous and evoked EEG activity were comparable: in the pre-stimulus (spontaneous) EEG both drugs increased the power in the low frequencies and decreased the power in the alpha range. In the post-stimulus (evoked) EEG the drugs decreased the power in all frequency bands. (2) Since in the low frequency range the drugs exhibited contrary effects upon spontaneous and evoked EEG activity, the pre-/post-stimulus relationship of the delta power was found to be the most sensitive measure for monitoring the cerebral bioavailability of the tested drugs. (3) The time courses of development of the effects of the two drugs were different: maximal effects of meperidine were obtained 85-105 min, and of imipramine 190-210 min after medication. The differences in the effect kinetics agreed with the different pharmacodynamics, with time constants for absorption and elimination of 40 min and 240 min for meperidine, and 240 min and 840 min for imipramine. (4) The most important difference between the 2 drugs was the different effect kinetic. Furthermore, in contrast to meperidine the effects of imipramine upon beta activity could not be separated from placebo, either in the spontaneous or in the evoked EEG activity.