Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges in Patients with Focal Epilepsy

Abstract Epileptiform spikes are brief (50-200 msec) sharply contoured waveforms in the electroencephalogram that are used to diagnose epilepsy and localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Fast ripples (FR, 200-600 Hz) are associated with epileptogenic brain tissue and may play critical roles in the epileptic network that generates seizures. We postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo EEG recordings from a cohort of 46 patients we found that spatially propagating FR, in the seizure onset zone (SOZ), often was followed by an epileptiform spike (p<0.05). Propagating FR, compared to non-propagating FR, exhibited a distinct frequency and larger power (p<1e-10) and were strongly phase coupled to the peak of delta oscillation DOWN states during non-REM sleep (p<1e-10). While FR propagation was rare, all FR occurred with the highest probability, in the inter-ictal epoch, within +/- 400 msec of certain epileptiform spikes (p<0.05). Thus, a distinct sub-population of epileptiform spikes in the SOZ, are preceded, and perhaps triggered by, propagating FR that are coordinated by the DOWN state during non-REM sleep. Our results also imply that FR propagation plays a role in the epileptic network.