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

Clin Neurophysiol. 2016 Jun;127(6):2489-99. doi: 10.1016/j.clinph.2016.03.022. Epub 2016 Apr 6.


Objective: High-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.

Methods: We 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.

Results: Increase 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).

Conclusion: Our 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.

Significance: Further 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.

Keywords: EEGLAB; High-gamma activity; Intracranial electrocorticography (ECoG) recording; Neurophysiology; Pathological and physiological high-frequency oscillations (HFOs); Pediatric epilepsy surgery; Phase–amplitude coupling; Receiver-operating characteristics (ROC) curve; Ripples; Subdural electroencephalography (EEG); Subtraction modulation index co-registered to MRI (SMICOM).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Brain Mapping*
  • Brain Waves*
  • Child
  • Epilepsy / physiopathology*
  • Female
  • Humans
  • Male
  • Sensorimotor Cortex / physiology
  • Sensorimotor Cortex / physiopathology*
  • Sleep