Population-based spectral characteristics of normal interictal scalp EEG inform diagnosis and treatment planning in focal epilepsy

Normal routine electroencephalograms (EEGs) can cause delays in the diagnosis and treatment of epilepsy, especially in drug-resistant patients and those without structural abnormalities. There is a need for alternative quantitative approaches that can inform clinical decisions when traditional visual EEG review is inconclusive. We leverage a large population EEG database (N = 13,652 recordings, 12,134 unique patients) and an independent cohort of patients with focal epilepsy (N = 121) to investigate whether normal EEG segments could support the diagnosis of focal epilepsy. We decomposed expertly graded normal EEGs (N = 6,242) using unsupervised tensor decomposition to extract the dominant spatio-spectral patterns present in a clinical population. We then, using the independent cohort of patients with focal epilepsy, evaluated whether pattern loadings of normal interictal EEG segments could classify focal epilepsy, the epileptogenic lobe, presence of lesions, and drug response. We obtained six physiological patterns of EEG spectral power and connectivity with distinct spatio-spectral signatures. Both pattern types together effectively differentiated patients with focal epilepsy from non-epileptic controls (mean AUC 0.78) but failed to classify the epileptogenic lobe. Spectral power-based patterns best classified drug-resistant epilepsy (mean AUC 0.73) and lesional epilepsy (mean AUC 0.67), albeit with high variability across patients. Our findings support that visibly normal patient EEGs contain subtle quantitative differences of clinical relevance. Further development may yield normal EEG-based computational biomarkers that can augment traditional EEG review and epilepsy care.