A Novel Focal Seizure Pattern Generated in Superficial Layers of the Olfactory Cortex

Abstract

Seizure patterns identified in focal epilepsies caused by diverse etiologies are likely due to different pathogenic mechanisms. We describe here a novel, region-specific focal seizure pattern that mimics seizure activity observed in a subpopulation of patients submitted to presurgical monitoring with intracerebral electrodes. Distinctive seizure-like events (SLEs) are induced in the olfactory regions by acute treatment of both tangential brain slices and the isolated guinea pig brain with the potassium channel blocker 4-aminopyridine. Analysis of field potentials, intracellular activities, and extracellular potassium changes demonstrates that SLEs in the piriform cortex initiate in the superficial layer 1 lacking principal neurons with an activity-dependent increase of extracellular potassium. SLE progression (but not onset) does not require the participation of synaptic transmission and is mediated by diffusion of potassium to deep cortical layers. The novel seizure pattern here described is not observed in other cortical regions; it is proposed to rely on the peculiar organization of the superficial piriform cortex layers, which are characterized by unmyelinated axons and perisynaptic astroglial envelopes. This study reveals a sequence of ictogenic events in the olfactory cortex that were never described before in other cortical structures and supports the notion that altered potassium homeostasis and unmyelinated fibers may represent a potential vehicle for focal ictogenesis. We describe a novel seizure pattern peculiar of the olfactory cortex that resembles focal seizures with low-voltage fast activity at onset observed in humans. The findings suggest that network mechanisms responsible for seizure onset can be region specific.

Two main focal seizure patterns revealed by intracerebral electroencephalographic biomarker analysis

“…Recently, we demonstrated a seizure pattern similar to the human P‐type pattern in the olfactory cortex of the isolated guinea pig brain. The onset of this seizure pattern correlated to extracellular potassium changes associated with increased synaptic activity; we proposed that seizure progression involved amplification of potassium release sustained by unmyelinated fiber depolarization . As for the human P pattern, the potassium changes occurring abruptly in the olfactory cortex induce a sharp‐on and sharp‐off potential shift coupled with LVFA.…”

“…As for the human P pattern, the potassium changes occurring abruptly in the olfactory cortex induce a sharp‐on and sharp‐off potential shift coupled with LVFA. Interestingly, in the experimental model synaptic transmission is abolished during a P‐type seizure (but not at its onset), possibly because of potassium‐induced fiber depolarization; in principle, this hypothesis could be verified in patients with an appropriate, ethically approved protocol designed for testing the response to low‐amplitude local stimulation of the EZ during P‐type seizures. The ictogenic mechanism proposed for P‐type seizures in the experimental animal model may be relevant to explain seizure generation in focal cortical dysplasia type IIb and in the cortex of TLE patients with and without associated dysplasia, where unmyelinated fibers in the subcortical white matter are pathologically augmented.…”

Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy

“…We also note that here we have focused on epileptic seizures that show SWDs. We hope to address in the future the case of seizures that do not include ictal SWDs, but remain instead within the dynamics of low-voltage fast-activity oscillations 19 , 28 , 50 , 51 .…”

How do we use in vitro models to understand epileptiform and ictal activity? A report of the TASK1‐WG4 group of the ILAE/AES Joint Translational Task Force

“…A recent study using the in toto guinea pig brain preparation showed that piriform cortex generates SLEs characterized by fast‐activity on a plateau potential (FAPP). FAPP SLEs are evoked by perfusion with the potassium channel antagonist 4‐AP and are similar to ictal activity seen in patients with frontal neocortical epilepsies . The piriform cortex generates fast activity nested within periodic slow oscillations at 0.1–0.5 Hz that precede the SLE.…”

“…Activity was recorded with glass capillary electrodes, at 3 KH z sampling in quasi‐ DC mode. (Modified from Avoli et al., 2016 and from Uva et al., 2017. )…”