Dual mechanisms of ictal high frequency oscillations in rhythmic onset seizures

ABSTRACT Objective High frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges have been proposed as a biomarker of epileptic brain sites and may also be a useful feature for seizure forecasting, with mixed results. Currently, pathological subclasses of HFOs have been defined primarily by frequency characteristics. Despite this, there has been limited investigation into the spatial context of HFOs with recruitment of local cortex into seizure discharging. We sought to further understand the biophysical underpinnings of ictal HFOs. Methods Here we examine ictal HFOs from multi-scale electrophysiological recordings during spontaneous human rhythmic onset seizures. We compare features of ictal discharges in both the seizure core and penumbra, as defined by multiunit activity patterns. Results We show marked differences in spectral features, unit coupling, and information theoretic characteristics of HFOs during ictal discharges before and after local seizure invasion. Furthermore, we tie these timing-related differences to different spatial domains of seizures, showing that eccentric, penumbral discharges are widely distributed and less useful for seizure localization, which may explain the variable utility of HFOs in seizure localization and forecasting. Interpretation We thus identify two distinct classes of ictal HFOs, implying two different mechanisms underlying pathological HFOs with contrasting significance for seizure localization.