Abstracts

Rationale: High frequency oscillations (HFOs; > 80 Hz) have been proposed to be robust markers of epileptic cortex; however their relation to oscillatory dynamics that regulate cortical networks remains unclear. The modulation high frequency amplitude by the phase of low frequency oscillations is thought to reflect an intrinsic neuronal hierarchical regulatory process involved in cortical processing. Here, we tested the hypothesis that dynamic cross-frequency interactions involving HFOs are concentrated within epileptic cortex. Methods: Intracranial electroencephalographic recordings from 17 children with medically-intractable epilepsy secondary to focal cortical dysplasia were obtained during seizures. A time-resolved analysis was performed to determine topographic concentrations and dynamic changes in cross-frequency amplitude-to-phase coupling (CFC). Results: HFO amplitudes (encompassing 80-300 Hz) were found to be modulated by the phase of theta and alpha rhythms (~5-12 Hz). CFC was significantly elevated in the seizure-onset zone compared to non-epileptic tissue (p<0.01). With time-resolved analysis, the phase of low frequency signals at which maximal HFO amplitudes were generated was found to evolve as seizures progressed, consistently shifting towards the trough of the oscillatory cycle at seizure termination. The findings were most significant for the modulation of HFOs by the phase of alpha-band oscillations (p<0.01). Conclusions: These results indicate that re-establishing normative CFC patterns is relevant for seizure termination and provide an opportunity for future therapeutic intervention. We also show that elevated cross-frequency interactions are concentrated within brain regions responsible for seizure initiation, and that their topographic mapping may be a novel method of pre-surgical mapping of epileptogenic tissue.