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.

Approximately one-third of individuals with chronic epilepsy, a condition resulting from uncontrolled brain activity, do not respond to medication. Animal models are widely used to investigate the mechanism underlying epilepsy, so better drug treatments can be developed for this disease. In such studies, epileptiform activity, assessed by EEG recordings, can be used as a marker for the development of the disease. However, the analysis of EEG recordings is typically done manually, which is time-consuming, subject to observer bias, error-prone, and lacks consistency and efficiency. In this paper, we develop a novel automated methodology for detecting and classifying epileptiform activity, which is tested using the intrahippocampal kainic acid (IHKA) mouse model, a representation of human temporal lobe epilepsy. For that, EEG/LFP recordings are obtained from biological experiments using the IHKA mouse model for data acquisition. We use a spike detection method that combines an improved version of the nonlinear energy operator (NEO) with the automatic NEO thresholding (ANT) algorithm. The proposed method is implemented in Python as an automated and time-efficient algorithm, given its adaptability to different spike and epileptiform event criteria, making it suitable for use in preclinical and potentially future clinical studies. Using our proposed methodology, we achieve a 93.1% accuracy in detecting epileptiform events and a 95.8% accuracy in classification. Moreover, the time for analysis of EEG recordings was reduced by 98.8% compared to manual analysis. Additionally, to demonstrate the potential of the algorithm for brain–machine interfaces (BMI) applications, we develop a hardware architecture and implement it using both an application-specific integrated circuit (ASIC) and a field programmable gate array (FPGA). The FPGA shows the feasibility of near real-time implementation, and for our ASIC implementation, we achieve a post-layout area of 9114 µm² with a dynamic power consumption of 16.09 μW using TSMC 40 nm technology.