Abstracts

Rationale: Our previous study reported that the amplitude of interictal high-frequency oscillations (HFOs) at 150-300 Hz were strongly coupled with the phase of slow wave at 0.5-1 Hz at nonepileptic low-order visual areas defined by electrical stimulation while preferentially coupled with that at 3-4 Hz at seizure onset zones. In the present study, we determined the spatial characteristics of phase-amplitude coupling between nonepileptic HFOs and slow wave0.5-1Hz, using a spatially-normalized brain template.  We also determined the effect of sleep stage on the strength of phase-amplitude coupling at each electrode site. Methods: We studied 1701 electrodes derived from 20 children with focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording. We developed a custom code in EEGLAB (Swartz Center for Computational Neuroscience, UC San Diego) to quantify modulation index (MI); thereby, MI(XHz)&(YHz) reflects the strength of coupling between amplitude of HFOsXHz and phase of slow-waveYHz. Each electrode site was transformed into a Talairach coordinate and plotted on the 3D normalized brain surface image, using FreeSurfer software. Electrode sites were classified either as ‘seizure onset zones’, ‘spiking areas outside seizure onset zones’, or ‘non-epileptic areas’, and the following analysis focused on ‘non-epileptic areas’. MI(150-300Hz)&(0.5-1Hz) and MI(150-300Hz)&(3-4Hz) during different sleep stages were delineated on the 3D normalized brain surface image. Regression coefficient of MI as a function of sleep stage (wakefulness [0], stage 1 [1], stage 2 [2], and slow-wave sleep [3]) was also calculated for each site.  Results: Across all sleep stages, MI(150-300Hz)&(0.5-1Hz) was greater in the ventral visual pathways including bilateral lingual, cuneus, lateral occipital and fusiform gyri. Analysis of regression coefficient revealed that both MI(150-300Hz)&(0.5-1Hz) and MI(150-300Hz)&(3-4Hz) increased as sleep deepened. More specifically, the regression coefficient for MI(150-300Hz)&(0.5-1Hz) was larger than that for MI(150-300Hz)&(3-4Hz) (mean: 7.9% per stage [95%CI: 6.9-8.8] vs 4.4% per stage [95%CI: 3.8-5.1]; p=0.001 on Bootstrap t-test). Conclusions: Phase-amplitude coupling between HFOs and slow-wave0.5-1Hz is strengthened during deeper non-REM sleep stages, particularly in the low-order and some of the high-order visual cortices. Physiological HFOs during non-REM sleep may be preferentially coupled with slow wave oscillations across large-scale visual networks. Further studies are warranted to determine the clinical utility of phase-amplitude coupling for presurgical localization of functionally-important areas. Funding: NIH grants NS064033 (to Eishi Asano)