Abstracts

Rationale: It remains unknown how useful interictal HFOs are as a biomarker of epileptogenicity. Some studies using intracranial ECoG reported that sites showing high rates of HFOs often turned out to be a part of the seizure onset zone (SOZ), and that resection of such sites was associated with a good seizure control. Others reported that interictal HFOs can be spontaneously generated by functionally-important regions such as non-epileptic visual, somatosensorimotor, and medial temporal regions. Here, we determined how well our empirical data replicated a tight association between the rate of interictal HFOs and SOZ responsible for habitual seizures.Methods: We studied 14 children with focal epilepsy who underwent two-stage epilepsy surgery using chronic ECoG recording (sampling rate: 1000 Hz). The patients had 104-146 subdural electrodes placed over the four lobes of the epileptic hemisphere, to determine the boundary between the presumed epileptogenic zone and functionally-important cortices. For each patient, an interictal slow-wave sleep epoch was chosen during the first night. At each channel, events of spontaneous HFOs>80 Hz, HFOs>150 Hz, and HFOs>250 Hz were visually detected, with a high-pass filter of 80, 150, and 250 Hz respectively, by an investigator blinded to the location of SOZ. Thereby, each HFOs>f Hz event was defined as an oscillatory event of ≥6 cycles with a frequency of ≥f Hz, a duration of <400 ms, an amplitude at least five times larger relative to an immediately-preceding baseline. A Kaiser-windowed sinc FIR filter (Kaiser beta: 3.4; filter order: ≤16) was applied, to minimize the risk of detection of a sharp transient mimicking HFOs following a strong high-pass filtering. In each patient, a mixed-model analysis was applied to determine if SOZ showed a higher rate of HFOs>f Hz compared to the non-SOZs sampled by ECoG. ‘SOZ’ was treated as a fixed effect, whereas ‘occipital’, ‘Rolandic’, and ‘medial temporal’ regions were treated as covariates, with ‘individual electrode’ treated as a random effect.Results: HFOs>150 Hz showed the best performance to predict the location of SOZ. The mixed-model analysis demonstrated that SOZ was associated with a significantly higher rate of HFOs>150 Hz compared to the non-SOZs in 5/14 patients (4.0 counts/min larger on average in these 5 patients). Conversely, the occipital region was associated with a significantly higher rate of HFOs>150 Hz compared to the extra-occipital regions in 6/14 patients (3.1 counts/min larger on average in these 6 patients). When all patients were taken into account, SOZ was associated with a higher rate of HFOs>150 Hz, by 1.6 counts/min on average, compared to the non-SOZs (uncorrected p-value: 0.03), but the difference failed to survive the Bonferroni correction. Likewise, no significant effects of covariates on the rate of HFOs>150 Hz were found.Conclusions: Our empirical data failed to replicate a statistically or clinically significant association between SOZ and a higher rate of HFOs. It may be too premature to determine the resection margin primarily based on the rate of interictal HFOs.