Investigating the influence of anti-seizure medications on aperiodic EEG activity

OBJECTIVE: Electroencephalography (EEG) signals comprise both oscillatory (periodic) and non-oscillatory (aperiodic) components. Aperiodic activity forms the 1/f-like background of the EEG power spectrum and can be characterised by parameters describing the offset and slope (1/f exponent). This study examined the effects of two antiseizure medications (ASMs), which reduce cortical excitability through different mechanisms of action, on aperiodic and periodic EEG activity. METHODS: Resting EEG was recorded with eyes open and closed from 13 healthy male volunteers at baseline and two hours after administration of lamotrigine (300 mg), levetiracetam (3000 mg), or placebo. Power spectra were computed using Welch's method. Aperiodic parameters were estimated using the specparam algorithm, and periodic activity was quantified after subtraction of the aperiodic component. RESULTS: In the eyes-open condition, lamotrigine significantly reduced both aperiodic offset and exponent relative to placebo, consistent with a flattening of the aperiodic spectrum, whereas levetiracetam reduced the exponent without significantly altering the offset. Neither drug significantly altered aperiodic exponent or offset during eyes-closed. Lamotrigine reduced corrected theta power in both conditions and alpha power during eyes-open, whereas levetiracetam increased beta power in both conditions and reduced gamma power during eyes-closed. CONCLUSIONS: Both lamotrigine and levetiracetam altered aperiodic and periodic EEG activity, with aperiodic effects observed only during eyes-open. SIGNIFICANCE: Aperiodic EEG measures may provide a non-invasive approach for characterising ASM-related neurophysiological effects and may help elucidate how distinct pharmacological mechanisms influence large-scale cortical activity.