Abstracts

Rationale: High-frequency oscillations (HFOs) (80-500 Hz) are recorded in mesial temporal regions of epileptic patients as well as in animal models of temporal lobe epilepsy (TLE). They are mostly related to interictal spikes, occur more frequently during periods of slow-wave sleep, and may reflect seizure onset zones. However, the spatial and temporal characteristics of HFOs following the initial status epilepticus (SE) are poorly defined. In this study, we have addressed the developmental pattern of HFOs in the pilocarpine model of TLE and performed continuous in vivo recordings in parahippocampal regions and in the hippocampus following SE. Methods: Seven rats were implanted with bipolar depth electrodes aimed at the dentate gyrus, CA3 region, subiculum and entorhinal cortex, 3 days after an initial pilocarpine-induced SE (380 mg/kg, i.p.). Local field potential (LFP) recordings were then performed on a 24-hr basis, from the 4th to the 15th day after SE. Ten minutes slow-wave sleep periods were selected for analysis. Raw LFP recordings were band-pass filtered and then normalized. Peaks that crossed a standard threshold (3 SD) for at least 3 consecutive cycles were kept for analysis. Rates (number of events/day) of interictal spikes without HFOs or co-occurring with fast ripples and with ripples were calculated. Results: The first spontaneous seizure occurred after a mean latency of 6.1 2.5 (SD) days from SE. Seizures (duration : 77.4 35.2 s, n = 155) were observed in every rat and were characterised by a cluster occurring between the 9th and the 12th day after SE. Different developmental patterns of interictal spike rates (n = 12,886) were observed depending on the co-occurrence with HFOs. Rates of interictal spikes without HFOs (74.4 4.4 % of all recorded interictal spikes) increased in every regions when seizure rates were low. On the contrary, rates of interictal spikes with fast ripples (4.9 4.6 %) first increased in parahippocampal regions and when seizure rates were low, but increased in the hippocampus only when seizure rates were high (between the 9th and 12th day of recording). Interictal spikes with ripples (9.0 3.6 %) showed a similar developmental pattern, but relation to seizure occurrence was less specific than when considering interictal spikes with fast ripples. Rates of interictal spikes with ripples also significantly decreased over time in the hippocampus (r2= -0.66, p < 0.05) and in the entorhinal cortex (r2= -0.67, p < 0.05), suggesting that they may be replaced over time by fast ripples in some regions. Conclusions: Interictal spikes may point to different dynamic processes that underlie epileptogenesis, depending on their co-occurrence with HFOs. Rates of interictal spikes with fast ripples showed a better relation with seizure occurrence and we observed different patterns of evolution depending on the region in which they were recorded. These results thus suggest that interictal spikes with fast ripples reflect a dynamic pathological process that first involves parahippocampal structures and that progressively brings the hippocampus close to seizure occurrence.