Abstracts

Rationale: Non-rapid eye movement (NREM) sleep facilitates the occurrence of epileptiform activity such as spikes and high frequency oscillations (HFOs). We sought to determine if NREM sleep does this uniformly or if some events within NREM sleep are particularly facilitating epileptiform discharges. Slow oscillations in neuronal excitability, commonly referred to as "up" (depolarizing) and "down" (hyperpolarizing) states, represent an important feature of the EEG during NREM sleep. However, their role in modulating epileptic spikes and HFOs remains unknown. Here we addressed this point by studying patients with therapy-refractory epilepsy undergoing combined scalp-intracerebral EEG recordings for diagnostic work-up. Methods: We selected patients who had 1) at least 1 intracranial frontal lobe channel with > 5 spikes during the first N2 and N3 sleep cycle, and 2) at least 1 intracranial frontal lobe channel without epileptic activity and outside of lesional tissue ("healthy" channel). Slow oscillations were automatically detected on scalp F3 and F4 electrodes, and considered generalized when slow oscillations included ≥50% of healthy frontal intracranial EEG channels. We manually marked spikes and HFOs (80-250 Hz) during the 20% of generalized slow oscillations with highest amplitude during N2 and N3 sleep of the first sleep cycle and during control segments of low amplitude or non-generalized slow waves during the same sleep period. A slow oscillation comprised a surface negative wave (presumptive hyperpolarizing state), and the preceding and following surface positive waves (presumptive depolarizing state). We compared the density of spikes and HFOs in these two states. Results: We included 8 patients (5 men; mean age: 34.8±7.6 y) for this analysis. The mean duration of N2 and N3 sleep of the first sleep cycle was 64 min; the mean across patients of the total duration of generalized slow oscillations was 10 min. Out of a total of 457 spikes identified during N2 and N3 sleep, 359 (78%) occurred during the generalized slow oscillations (p<.001). HFOs were marked in 5 patients. In these 5 patients 3936 (67%) of a total of 5857 HFOs were marked during the generalized slow oscillations. The surface negative component of the slow oscillations (presumptive "down" hyperpolarizing state) had an average duration of 0.51 seconds and occupied 36% of the slow oscillation time but included the occurrence of 44% of spikes and of 42% of the HFOs (p<.001 for both events, Figure 1). Conclusions: Our results demonstrate that generalized slow oscillations occurring during NREM sleep are characterized by significantly higher spike and HFO density in patients with therapy-refractory epilepsy. Surprisingly, both pathologic events appear to predominate during the presumptive "down" hyperpolarizing state of the slow EEG oscillation. This finding suggests that in the epileptic brain periods coinciding with active inhibition are associated with increased occurrence of interictal spikes and HFOs.