Dynamic modulation of epileptic high frequency oscillations by the phase of slower cortical rhythms

•Pathological high frequency oscillations are modulated by the phase of slower cortical rhythms in epileptic cortex.•Cross-frequency coupling occurs at a consistent oscillatory phase at seizure termination.•Cross-frequency coupling may be a marker of epileptogenicity and useful as a target for future interventions.•These findings are relevant for understanding oscillatory dynamics underlying seizures.

Pathological high frequency oscillations (pHFOs) have been proposed to be robust markers of epileptic cortex. Oscillatory activity below this frequency range has been shown to be modulated by phase of lower frequency oscillations. Here, we tested the hypothesis that dynamic cross-frequency interactions involving pHFOs are concentrated within the epileptogenic cortex. Intracranial electroencephalographic recordings from 17 children with medically-intractable epilepsy secondary to focal cortical dysplasia were obtained. A time-resolved analysis was performed to determine topographic concentrations and dynamic changes in cross-frequency amplitude-to-phase coupling (CFC). CFC between pHFOs and the phase of theta and alpha rhythms was found to be significantly elevated in the seizure-onset zone compared to non-epileptic regions (p < 0.01). Data simulations showed that elevated CFC could not be attributed to the presence of sharp transients or other signal properties. The phase of low frequency oscillations at which pHFO amplitudes were maximal was inconsistent at seizure initiation, yet consistently at the trough of the low frequency rhythm at seizure termination. Amplitudes of pHFOs were most significantly modulated by the phase of alpha-band oscillations (p < 0.01). These results suggest that increased CFC between pHFO amplitude and alpha phase may constitute a marker of epileptogenic brain areas and may be relevant for understanding seizure dynamics.