EEG Spectral Exponents and Visual Chirp Responses Mirror Anti-Seizure Medication Load in Refractory Focal Epilepsy

Objective: Quantitative markers of cortical excitability may help identify responders to anti-seizure medications (ASMs). We studied the relationship between ASM load and two electroencephalography (EEG) markers of cortical excitability in people with refractory epilepsy. Methods: We included individuals with refractory focal epilepsy undergoing presurgical evaluation, involving ASM tapering and sleep deprivation. We obtained daily resting state EEG and EEG responses to visual stimulation at linearly increasing flash frequency (10–40 Hz chirp). We extracted the aperiodic exponent from resting state EEG power spectra and analysed chirp response at driving and second-order harmonic frequencies. We modelled ASM load, which we related to the EEG markers using linear mixed-effects regression. Results: Forty-eight subjects (median age 34 years, age range 16–62 years, 19 females) participated. The spectral exponent became less negative with ASM load reduction (p = 0.02), mainly attributable to reduced low-frequency power. Lowering ASM load increased the harmonic response to chirp stimulation (p = 0.004), also after accounting for sleep deprivation (p = 0.02), but did not affect the driving response. ASM tapering specifically increased harmonic responses to high stimulation frequencies (27–40 Hz, p = 0.01). Interpretation: Resting state EEG spectral exponents and visual chirp responses reflect ASM load in refractory epilepsy. Low-frequency spectral changes in resting state EEG may only mirror ASM-induced spectral slowing. Visual chirp stimulation reveals enhanced harmonic EEG responses during low ASM loads, likely due to both increased high gamma activity and increased response to visual perturbations. Implementation of the markers would need normative values to reduce the delay to individually optimised treatment regimens.