Abstract

High-frequency oscillations (HFOs, ripples 80–250 Hz, fast ripples 250–500 Hz) are biomarkers of epileptic tissue. They are most commonly observed over areas generating seizures and increase in occurrence during the ictal compared to the interictal period. It has been hypothesized that their rate correlates with the severity of epilepsy and seizure in affected individuals. In the present study, it was aimed to investigate whether the HFO count mirrors the observed behavioral seizure severity using a kainate rat model for temporal lobe epilepsy. Seizures were selected during the chronic epilepsy phase of this model and classified by behavioral severity according to the Racine scale. Seizures with Racine scale 5&6 were considered generalized and severe. HFOs were marked in 24 seizures during a preictal, ictal, and postictal EEG segment. The duration covered by the HFO during these different segments was analyzed and compared between mild and severe seizures. HFOs were significantly increased during ictal periods (p < 0.001) and significantly decreased during postictal periods (p < 0.03) compared to the ictal segment. Ictal ripples (p = 0.04) as well as fast ripples (p = 0.02) were significantly higher in severe seizures compared to mild seizures. The present study demonstrates that ictal HFO occurrence mirrors seizure severity in a chronic focal epilepsy model in rats. This is similar to recent observations in patients with refractory mesio-temporal lobe epilepsy. Moreover, postictal HFO decrease might reflect postictal inhibition of epileptic activity. Overall results provide additional evidence that HFOs can be used as biomarkers for measuring seizure severity in epilepsy.

Highlights

  • High-frequency oscillations (HFOs) between 80 and 500 Hz are biomarkers for epileptic tissue

  • We investigate HFO occurrence during the preictal, ictal, and postictal periods in rats with focal mesio-temporal epilepsy and hypothesized that seizure severity is mirrored by HFO occurrence

  • No rat died during status epilepticus or during the following observation period; two rats died during the anesthesia process and preparation prior to status epilepticus

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Summary

Introduction

High-frequency oscillations (HFOs) between 80 and 500 Hz are biomarkers for epileptic tissue. They were described recorded with intracranial microelectrodes and closely linked to mesiotemporal structures that generated spontaneous seizures (Bragin et al, 1999). Most of the studies investigating whether HFOs could help to localize epileptic tissue focused on the analysis of interictal HFOs. ictal gamma oscillations and HFOs can be identified during epileptic seizures (Jirsch et al, 2006; Jacobs et al, 2009; Weiss et al, 2015; Smith et al, 2020). It could be shown that HFOs increase systematically at seizure onset independent of the seizure onset pattern and etiology (Perucca et al, 2014)

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