Spontaneous fast-ultradian dynamics of polymorphic interictal events in drug-resistant focal epilepsy

Abstract

AbstractObjectiveWe studied the rate dynamics of interictal events occurring over fast-ultradian time scales, as commonly examined in clinics to guide surgical planning in epilepsy.MethodsStereoelectroencephalography (SEEG) traces of 35 patients with good surgical outcome (Engel I) were analyzed. For this, we developed a general data mining method aimed at clustering the plethora of transient waveform shapes including interictal epileptiform discharges (IEDs), and assessed the temporal fluctuations in the capability to map the epileptogenic zone (EZ) of each type of event.ResultsWe found that the fast-ultradian dynamics of the IEDs rate may effectively impair the precision of EZ identification, and appear to occur spontaneously, that is, not triggered by or exclusively associated with a particular cognitive task, wakefulness, sleep, seizure occurrence, post-ictal state or antiepileptic drug withdrawal. Propagation of IEDs from the EZ to the propagation zone (PZ) could explain the observed fast-ultradian fluctuations in a reduced fraction of the analyzed patients, suggesting that other factors like the excitability of the epileptogenic tissue could play a more relevant role. A novel link was found between the fast-ultradian dynamics of the overall rate of polymorphic events and the rate of specific IEDs subtypes. We exploited this feature to estimate in each patient the 5 min interictal epoch for near-optimal EZ and resected zone (RZ) localization, which resulted at the population level better than those obtained using either 1) the whole time series available in each patient (P = 0.084 for EZ, P < 0.001 for RZ, Wilcoxon signed rank test) and 2) 5 min epochs randomly sampled from the interictal recordings of each patient (P < 0.05 for EZ, P < 0.001 for RZ, 105random samplings).SignificanceOur results highlight the relevance of the fast-ultradian IEDs dynamics in mapping the EZ, and show how it can be prospectively estimated to inform surgical planning in epilepsy.Key PointsThe rate of IED observed in SEEG recordings undergoes spontaneous fluctuations over fast-ultradian time scales.The fast-ultradian dynamics of the IED rate may impair the EZ identification and hence are clinically relevant for surgical planning.Propagation does not fully explain the fast-ultradian dynamics of the IED rate constraining the precision to localize the EZ.Interictal epochs, as commonly examined in clinics, producing near-optimal EZ mapping can be inferred based solely on the LFP dynamics.Fluctuations of the AUPREC based on epileptic and non-epileptic events are linked to scale-free and scale-rich processes, respectively.