Interictal high-frequency oscillations generated by seizure onset and eloquent areas may be differentially coupled with different slow waves

• Interictal HFOs were noted in seizure-onset and sensorimotor–visual sites during sleep.
• Epileptogenic HFOs may be more preferentially coupled with slow waves of 3–4 Hz.
• Physiologic HFOs may be more preferentially coupled with slow waves of 0.5–1 Hz.

ObjectiveHigh-frequency oscillations (HFOs) can be spontaneously generated by seizure-onset and functionally-important areas. We determined if consideration of the spectral frequency bands of coupled slow-waves could distinguish between epileptogenic and physiological HFOs.MethodsWe studied a consecutive series of 13 children with focal epilepsy who underwent extraoperative electrocorticography. We measured the occurrence rate of HFOs during slow-wave sleep at each electrode site. We subsequently determined the performance of HFO rate for localization of seizure-onset sites and undesirable detection of nonepileptic sensorimotor–visual sites defined by neurostimulation. We likewise determined the predictive performance of modulation index: MI(XHz)&(YHz), reflecting the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. The predictive accuracy was quantified using the area under the curve (AUC) on receiver-operating characteristics analysis.ResultsIncrease in HFO rate localized seizure-onset sites (AUC ⩾ 0.72; p < 0.001), but also undesirably detected nonepileptic sensorimotor–visual sites (AUC ⩾ 0.58; p < 0.001). Increase in MI(HFOs)&(3–4Hz) also detected both seizure-onset (AUC ⩾ 0.74; p < 0.001) and nonepileptic sensorimotor–visual sites (AUC ⩾ 0.59; p < 0.001). Increase in subtraction-MIHFOs [defined as subtraction of MI(HFOs)&(0.5–1Hz) from MI(HFOs)&(3–4Hz)] localized seizure-onset sites (AUC ⩾ 0.71; p < 0.001), but rather avoided detection of nonepileptic sensorimotor–visual sites (AUC ⩽ 0.42; p < 0.001).ConclusionOur data suggest that epileptogenic HFOs may be coupled with slow-wave3–4Hz more preferentially than slow-wave0.5–1Hz, whereas physiologic HFOs with slow-wave0.5–1Hz more preferentially than slow-wave3–4Hz during slow-wave sleep.SignificanceFurther studies in larger samples are warranted to determine if consideration of the spectral frequency bands of slow-waves coupled with HFOs can positively contribute to presurgical evaluation of patients with focal epilepsy.