The Cause of the Imbalance in the Neuronal Network Leading to Seizure Activity Can Be Predicted by the Electrographic Pattern of the Seizure Onset

Abstract

This study investigates the temporal dynamics of ictal electrical activity induced by injection of the GABA A receptor antagonist bicuculline, and the glutamate agonist kainic acid, into the CA3 area of hippocampus. Experiments were conducted in freely moving adult Wistar rats implanted with microelectrodes in multiple brain areas. Wide-band electrical activity (0.1-3000 Hz) was recorded, and the latency of seizure onset as well as the pattern of electrical activity were investigated for each drug. The latencies between injection and the occurrence of first epileptiform events were 3.93 Ϯ 2.76 (ϮSTD) min for bicuculline and 6.37 Ϯ 7.66 min for kainic acid, suggesting the existence of powerful seizure-suppressive mechanisms in the brain. Bicuculline evoked high-amplitude rhythmic epileptiform events at the site of injection which resembled interictal EEG spikes and rapidly propagated to adjacent and remote brain areas. Kainic acid evoked a completely different pattern with a gradual increase in the amplitude of 30 -80 Hz activity. Whereas there was strong temporal correlation between EEG events at the site of bicuculline injection and discharges in distant areas, much less correlation was seen with kainic acid injection. Both patterns were followed by generalized ictal EEG discharges and behavioral seizures. Our results illustrate that the same area of the brain can trigger seizures with different electrographic patterns. The knowledge of the network mechanisms underlying these two distinct electrographic patterns might be helpful in designing differential strategies for preventing seizure occurrence.

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

“…As in our previous studies involving hippocampal picrotoxin infusions , observations of the rats following infusions and between infusion days, did not reveal infusion-induced motor convulsions or more subtle indicators of seizure development, such as facial twitches, tremor, movement arrest or wet-dog shakes, which may result from higher doses of GABA antagonists (Bragin et al 2009). Furthermore, our electrophysiological studies did not indicate electrophysiological seizure signs (see below).…”

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

“…3). Excitatory field events similar to PID have been detected just before seizures in animal models 6,8,15,43,44 . PID do not involve barrages of hyperpolarizing synaptic events which may act as an inhibitory restraint, to protect against the spread of seizure-like activities 45 .…”

“…3b). The amplitude of stable PID (185±106 μV, 95% CI: , n=66 events from 8 slices) was significantly higher than that of simultaneous IID (49±24 μV, 95% CI: [42][43][44][45][46][47][48][49][50][51][52][53][54][55], n=66 events from 8 slices) (Wilcoxon test, Z(7)=3.99, P<0.01) (Fig. 3e) Fig.…”

Activation of specific neuronal networks leads to different seizure onset types

“…3 LVF and HYP seizures may mirror the activity of distinct limbic structures. 4 Accordingly, Velasco et al 2 have reported that LVF seizures rest on the activity of hippocampal and parahippocampal networks, whereas HYP seizures originate from local circuits in the hippocampal formation. In addition, TLE patients presenting with HYP seizures have histopathological patterns of atrophy that are consistent with hippocampal sclerosis, whereas LVF seizures are linked to a more diffuse and bilateral distribution of atrophy.…”