Mapping Propagation of Interictal Spikes, Ripples, and Fast Ripples in Intracranial EEG of Children with Refractory Epilepsy

Abstract

Studies on intracranial electroencephalography (icEEG) recordings of patients with drug resistant epilepsy (DRE) show that epilepsy biomarkers propagate in time across brain areas. Here, we propose a novel method that estimates critical features of these propagations for different epilepsy biomarkers (spikes, ripples, and fast ripples), and assess their common onset as a reliable biomarker of the epileptogenic zone (EZ). For each biomarker, an automatic algorithm ranked the icEEG electrodes according to their timing occurrence in propagations and finally dichotomized them as onset or spread. We validated our algorithm on icEEG recordings of 8 children with DRE having a good surgical outcome (Engel score = 1). We estimated the overlap of the onset, spread, and entire zone of propagation with the resection (RZ) and the seizure onset zone (SOZ). Spike and ripple propagations were seen in all patients, whereas fast ripple propagations were seen in 6 patients. Spike, ripple, and fast ripple propagations had a mean duration of 28.3 ± 24.3 ms, 38.7 ± 37 ms, and 25 ± 14 ms respectively. Onset electrodes predicted the RZ and SOZ with higher specificity compared to the entire zone for all three biomarkers (p<0.05). Overlap of spike and ripple onsets presented a higher specificity than each separate biomarker onset: for the SOZ, the onsets overlap was more specific (97.89 ± 2.36) than the ripple onset (p=0.031); for the RZ, the onsets overlap was more specific (98.48 ± 1.5) than the spike onset (p=0.016). Yet, the entire zone for spike and ripple propagations predicted the RZ with higher sensitivity compared to each biomarker's onset (or spread) (p<0.05). We present, for the first time, preliminary evidence from icEEG data that fast ripples propagate in time across large areas of the brain. The onsets overlap of spike and ripple propagations constitutes an extremely specific (but not sensitive) biomarker of the EZ, compared to areas of spread (and entire areas) in propagation. Clinical Relevance-Our novel method can identify propagation events of epilepsy biomarkers, quantify their features, and delineate their overlapping onset, which constitutes an extremely specific biomarker of the EZ and may benefit children with DRE undergoing epilepsy neurosurgery.

Functional connectivity discriminates epileptogenic states and predicts surgical outcome in children with drug resistant epilepsy

“…Moreover, our findings do not provide information regarding the directionality of information flow between epileptogenic and non-epileptogenic regions. Directed connectivity measures may help to map propagation phenomena of ictal and interictal activity 53 , 54 . We also used only one simple measure of graph-theory (i.e., nodal strength) extensively studied in epilepsy 8 , 13 , 55 that might not fully interpret the complexity of abnormal brain networks 56 .…”

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

“…FR Propagate in the SOZ and possibly outside the SOZ Prior studies using SEEG recordings have demonstrated that both ripples (Tamilia et al, 2021(Tamilia et al, , 2018 and fast ripples (Jahromi et al, 2021;Otárula et al, 2019) propagate within the SOZ. These studies did not distinguish HFOs superimposed on spikes from HFOs superimposed on oscillations and thus it is not clear if the propagation of the HFOs on spikes, in these studies, can be attributed to propagation of either the spike, the HFO, or both.…”

“…We chose to focus on FR rather than ripples to reduce contamination from normal HFO (Frauscher et al, 2018), but we are aware the generation and propagation of FR could spatially restricted compared to ripples (Bragin et al, 2002;Otárula et al, 2019). Also, we and others use the term "propagate" to explain the time lags observed between FR (Jahromi et al, 2021;Otárula et al, 2019), but recognize delays between FR might be due to a common synaptic driver. Thus, support for our hypothesis would require first, evidence that FR propagate, and we performed several analyses to demonstrate what can best be interpreted as propagation.…”

“…Pathological high-frequency oscillations (HFO) are also found in the epileptic brain and are believed to correspond, at the resolution of the local field potential, with abnormal bursting of predominately excitatory cells (Bragin et al, 2007(Bragin et al, , 2000. Interictal pathological HFO, which include fast ripples (FR; and some ripples , are associated with the SOZ and like interictal spikes, there is some evidence pathological HFO can propagate within the SOZ (Jahromi et al, 2021;Otárula et al, 2019). Pathological HFOs can occur alone, but often occur with interictal spikes (Jacobs et al, 2008;Urrestarazu et al, 2007), especially in the SOZ (Weiss et al, 2016).…”

Replay of Interictal Sequential Activity Shapes the Epileptic Network Dynamics

“…Their value in addressing issues such as seizure onset zone (SOZ) localization has been validated [32][33][34][35][36] . Furthermore, the approximate synchrony of recurrent interictal electrographic events across different nodes provides rich spatiotemporal information about the epileptic network 22,[37][38][39] . The earlier discharges within these collective activities have a higher probability to be in the epileptic origin 23,40,41 .…”