From Spike to Seizure: Transformation or Transition?

ObjectiveThe transition from interictal discharges to ictal high-frequency activity (HFA) remains poorly understood. We investigated whether spike-associated high-frequency oscillations (Sp-HFOs) during interictal and preictal periods contribute to the emergence of ictal HFA. MethodsWe retrospectively analyzed the interictal to ictal transition in seizures from six patients with drug-resistant focal epilepsy who underwent stereo-EEG and subsequent surgical resection. Various interictal periods preceding seizure onset were selected for comparison. Time- frequency analysis (TFA) was used to characterize Sp-HFOs and ictal HFA. Frequency overlap was quantified using the I-Fusion metric, and linear regression assessed changes in I-Fusion values over time, with R{superscript 2} indicating correlation strength. ResultsVisual analysis of the time series revealed a preictal phase in all patients, during which brief high-frequency activity gradually emerged within spikes (Sp-HFOs), ultimately transitioning into sustained ictal HFA at the same frequency. TFA demonstrated increasing frequency similarity with time between Sp-HFOs and ictal HFA. I-Fusion values and R{superscript 2} coefficients rose consistently, indicating a progressive convergence in frequency content. Notably, Sp-HFOs and ictal HFA shared narrow-band frequency features within the same electrode contacts, especially in the epileptogenic zone (EZ). InterpretationOur findings support a dynamic, frequency-specific evolution from interictal Sp-HFOs to ictal HFA, suggesting that seizure onset is preceded by a gradual preparatory phase rather than an abrupt transformation. The progressive nature and spectral continuity of Sp-HFOs may reflect increasing neuronal synchrony, providing potential early biomarkers for seizure prediction and improved localization of the EZ.