FR are most probable on or within +/− 400 ms of an epileptiform discharge

Propagating FR are more likely to be followed by epileptiform discharge

Propagating FR at the origin exhibit delay dependent distinct spectral frequency and power

FR are coupled to the peak of delta, FR-delta coupling determines the probability of propagation

Propagating FR may be involved in spontaneously eliciting epileptiform discharges

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

focal epilepsy

epileptiform discharge

fast ripple

slow wave sleep

down state

high-frequency oscillation

high-frequency oscillation

non-seizure onset zone

non-rapid eye movement sleep

generalized linear mixed-effects model

power spectral density

iEEG recordings are available upon reasonable request from the authors. The iEEG data used for figure generation are available at https://www.zenodo.org/record/6529724#.Ynkv4YfML9Y and https://zenodo.org/record/6532325#.YnlLF4fML9Y. HFO and electrode contact MongoDB JSON files are available at https://zenodo.org/record/6451900#.YmgQie3ML9Y and.

open-source code for statistics and figure generation from https://github.com/shenweiss/publishedcode.

© 2022 Published by Elsevier Inc.