Cortical oscillations to measure anti-epileptic drug activity in clinical trials

The frequency analysis of electroencephalographic (EEG) activity, either spontaneous or evoked by transcranial magnetic stimulation (TMS-EEG), is a powerful tool to investigate changes in brain activity and excitability following the administration of antiepileptic drugs (AEDs). However, a systematic evaluation of the effect of AEDs on spontaneous and TMS-induced brain oscillations has not yet been provided. We studied the effects of lamotrigine, levetiracetam, and of a novel potassium channel opener (XEN1101) on TMS-induced and spontaneous brain oscillations in a group of healthy volunteers. Levetiracetam suppressed TMS-induced theta, alpha and beta power, whereas lamotrigine increased TMS-induced alpha power. XEN1101 decreased TMS-induced delta, theta and beta power. Resting-state EEG showed a decrease of theta band power after lamotrigine intake. Levetiracetam increased theta, beta and gamma power, while XEN1101 produced an increase of delta, theta, beta and gamma power. Different AEDs induce specific patterns of power changes in spontaneous and TMS-induced brain oscillations. Spontaneous and TMS-induced cortical oscillations represent a powerful tool to characterize the effect of AEDs on in vivo brain activity. Spectral fingerprints of specific AEDs should be further investigated to provide robust and objective biomarkers of biological effect in human clinical trials.