Spike-fast activity interplay: A gateway to seizure

The 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.

We retrospectively analyzed the interictal to ictal transition in seizures from six patients with drug-resistant focal epilepsy who underwent stereo-electroencephalography (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 measured using the Ideal Fusion (I-Fusion) metric, a novel metric inspired by the F-measure that integrates frequency range overlap and band matching. I-Fusion values range from 0 (no overlap) to 1 (perfect match). Linear regression analyzed changes in I-Fusion values over time, with R² indicating the strength of the correlation.

Visual analysis of the time series revealed a preictal phase in all patients, during which brief HFA 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 R² 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).

Our 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.