Distinct Eeg Seizure Patterns Reflect Different Seizure

33 Low-voltage fast-(LVF) and hypersynchronous-(HYP) seizure onset patterns can be recognized 34 in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80-200 Hz) 35 and fast ripples (250-500 Hz) have been linked to each pattern, with ripples predominating 36 during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine 37 model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the 38 contribution of neural networks with distinct transmitter signaling characteristics. Here, we 39 tested this hypothesis by analysing the seizure activity induced with the K + channel blocker 4-40 aminopyridine (4AP, 4-5 mg/kg, i.p.)-which enhances both glutamatergic and GABAergic 41 transmission-or the GABA A receptor antagonist picrotoxin (3-5 mg/kg, i.p.); rats were 42 implanted with electrodes in the hippocampus, the entorhinal cortex and the subiculum. We 43 found that LVF-onset occurred in 82% of 4AP-induced seizures while seizures following 44 picrotoxin were always HYP. In addition, HFO analysis revealed that 4AP-induced LVF seizures 45 were associated to higher ripple rates compared to fast ripples (p<0.05), whereas picrotoxin-46 induced seizures contained higher rates of fast ripples compared to ripples (p<0.05). These 47 results support the hypothesis that two distinct patterns of seizure onset result from different 48 pathophysiological mechanisms.