Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome

Abstract

Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment-how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of ϳ30 s for a broad area of cortex (8 ϫ 8 cm) to be recruited into the seizure, at an estimated speed of ϳ4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure.

Spatiotemporal Mapping of Interictal Spike Propagation: A Novel Methodology Applied to Pediatric Intracranial EEG Recordings

“…This finding aligns with recent work by Martinet et al (29), who mapped the spatiotemporal propagation of neocortical seizures and demonstrated that more consistent and organized ictal recruitment patterns were associated with improved surgical outcomes. Critically, these authors relied on a similar application of the Moran Index to analyze ictal recruitment latency maps, maximizing the comparability of the findings.…”

“…An illustration of the Moran Index applied to various spatial maps is provided in Figure 5 using simulated data. As the simulation demonstrates the Moran Index ranges from −1 (perfect anti-autocorrelation between neighboring channels) to +1 (perfect autocorrelation between neighboring channels), with 0 indicating no pattern of spatial autocorrelation (29). …”

“…Electrode mapping was performed by an author (Samuel B. Tomlinson) blind to patient identity and confirmed by the senior author (Eric D. Marsh) prior to analysis. We acknowledge that this 2D approach does not capture the precise physical distance between electrode pairs, which is influenced by the 3D structure of the brain and the sulcal/gyral patterns beneath the arrays (29). However, approximating spatial relationships among channels using 2D schematics is common practice in the literature when coregistered MRI and CT imaging studies are unavailable.…”

“…Channels that consistently appeared early in spike sequences thus exhibited a left-shifted CPD. Then, to visualize recruitment latencies across electrodes, recruitment latency maps were constructed (Figure 4B, right), with warmer colors representing shorter mean recruitment times (29). This approach allowed us to visualize the global movement of spikes from “source” regions with lower recruitment latencies (warmer colors) to “sink” regions with higher recruitment latencies (cooler colors).…”

“…where N is the number of channels, F i is the spike frequency of channel i (spikes per minute), F avg is the mean spike frequency across all channels, and w ij is the spatial “weight” between channels i and j (29). For recruitment latency maps, the same equation was used, but F i corresponded to the mean recruitment latency of channel i (ms) and F avg was the mean recruitment latency across channels.…”