Abstracts

Rationale: In animal studies, both seizures and interictal spikes induce synaptic potentiation. Recent evidence suggests that electroencephalogram (EEG) slow wave activity (SWA) during sleep reflects synaptic potentiation during wake, and that its homeostatic decrease during the night is associated with synaptic renormalization and its beneficial effects. Here we asked whether epileptic activity induces plastic changes that can be revealed by high-density EEG recordings during sleep. Methods: 15 drug-refractory focal epilepsy patients (mean age 43 SD 14, 9 females) were recruited at the Epilepsy Monitoring Unit of the University of Wisconsin. Individual patients presented variable seizure focus localization on 10-20 EEG clinical readings: left temporal (n=4), left frontal (n=4), right temporal (n=2), bilateral temporal (n=2), bilateral frontal (n=1), right parietal (n=1), or right extra-temporal (n=1). 256 electrodes high-density EEG overnight recordings were performed in patients and compared to those performed in 15 age and gender matched healthy volunteers (mean age 43 SD 14, 10 females). Epochs of steady non rapid eye movement (NREM) sleep and REM sleep were then extracted from the recordings for further preprocessing. EEG data were filtered from 1 to 40 Hz, and semi-automated artifact rejection was used to further select clean epochs and channels. Individual NREM slow waves were also detected and the overnight decrease in slow wave negative slope was computed as described in previous work. Topographic values of SWA (delta) and spindle power as well as the overnight decrease in slope of slow waves for each EEG channel were converted to 2D images and statistical analyses were performed using Statistical Parametric Mapping and Statistical Non Parametric Mapping. All results were thresholded at family-wise error corrected p < 0.05. Results: Compared to controls, patients with epilepsy displayed increased NREM sleep SWA over widespread, bilateral scalp regions (Figure 1). This increase in SWA was only present during NREM sleep and was positively correlated with the frequency of generalized seizures in the 3-5 days preceding the recordings. Individual patients also showed local increases in NREM sleep SWA at scalp locations matching their seizure focus. This local SWA increase was positively correlated with the frequency of interictal spikes during the last hour of wakefulness preceding sleep (Figure 2). By contrast, frequent interictal spikes during NREM sleep predicted a reduced homeostatic decrease in the slope of sleep slow waves during the night, which in turn predicted reduced daytime learning. Patients also showed an increase in sleep spindles, which was negatively correlated with IQ. Conclusions: Altogether, these findings suggest that both seizures and interictal spikes can induce plastic changes in the human brain that can be sensitively detected by EEG markers of sleep homeostasis. Furthermore, abnormalities in sleep EEG markers are correlated with cognitive impairment, suggesting that not only seizures, but also interictal spikes can have negative consequences. Funding: Supported by a Grace Grant from the Lily's Fund for Epilepsy Research