The ictal wavefront is the spatiotemporal source of discharges during spontaneous human seizures

Abstract

The extensive distribution and simultaneous termination of seizures across cortical areas has led to the hypothesis that seizures are caused by large-scale coordinated networks spanning these areas. This view, however, is difficult to reconcile with most proposed mechanisms of seizure spread and termination, which operate on a cellular scale. We hypothesize that seizures evolve into self-organized structures wherein a small seizing territory projects high-intensity electrical signals over a broad cortical area. Here we investigate human seizures on both small and large electrophysiological scales. We show that the migrating edge of the seizing territory is the source of travelling waves of synaptic activity into adjacent cortical areas. As the seizure progresses, slow dynamics in induced activity from these waves indicate a weakening and eventual failure of their source. These observations support a parsimonious theory for how large-scale evolution and termination of seizures are driven from a small, migrating cortical area.

Multivariate regression methods for estimating velocity of ictal discharges from human microelectrode recordings

“…Evidence for traveling wave behavior of epileptiform discharges has been documented in several prior studies [5, 13, 14, 43–46], including one in which discharges recorded simultaneously in ECoG and microelectrodes, and analyzed separately, demonstrated aligned propagation directions [14]. This stands in contrast to the traditional view that the extended field of ictal discharges is a consequence of volume conduction from a spatially-constrained source, or alternatively that they arise simultaneously from a large cortical territory [18, 19, 47–50].…”

“…We next tested two LFP-based measures of ictal discharge timing: negative peak and point of maximal descent, both of which have been employed in prior studies [14, 39, 40]. The spatiotemporal distributions of ictal discharge event timing, estimated by each method respectively, are shown in Figure 2B–C for the example ictal discharge used in Figure 2A.…”

“…A number of studies have measured the temporal delay of epileptiform discharges in human scalp EEG, subdural [5, 43] and microelectrode array [13, 14, 44, 45] recordings. Various methods to measure propagation speed and direction have been proposed, from simple estimates based on the timing of signal extrema [5, 13, 14, 51], to more complicated estimates, such as coherence-based measurements [44], with wave speeds measured at 25–75 cm/sec.…”

“…Data were recorded from epilepsy patients undergoing chronic invasive EEG in preparation for surgical treatment [14, 25–28]. All patients provided informed consent prior to study involvement.…”

“…Discharge timing was identified from peak firing rate averaged across channels, using a threshold of 7 spikes per second and at least 100 ms separation between neighboring peaks, based on the expected maximum duration of 200 ms for an epileptiform sharp wave [2]. All electrical activity within 50 ms of a firing peak was considered part of the ictal discharge (Figure 1) [14, 31, 32]. …”