Abstracts

Rationale:
Synaptic down-scaling during sleep promotes memory consolidation and restoration of neuronal energetics. Decline in EEG Slow Wave Activity (SWA, i.e. delta power, 1-4 Hz) over the course of the night has been shown to be a reliable marker of homeostatic decreases in synaptic strength. Animal studies suggest that neuronal burst firing during sleep – such as the one triggered by epileptic spikes - may prevent synaptic downscaling. Previous studies in children with ESES as well as in an initial cohort of 15 patients with epilepsy also suggested that more frequent spikes during sleep led to reduced SWA decline. Here we wished to confirm and extend our previous results by assessing correlation between interictal spike frequency during sleep and SWA decline in a larger cohort of adult patients with drug-refractory epilepsy.  
Method:
50 drug refractory epileptic patients underwent high-density EEG recordings (HDEEG, 256 electrodes) over the course of a night in the Epilepsy Monitoring Unit of the University of Wisconsin, Madison. Interictal spikes were manually marked and verified by a certified epileptologist (MB) to derive average spike frequency (spikes per hour of sleep) for each recording. After sleep scoring using standard AASM criteria, HD-EEG data were filtered between 0,5 and 40 Hz, artifact rejection was performed using custom Matlab scripts to reject bad channels and bad epochs, and epochs containing only N2-N3 stages were selected. We applied a Fourier transform at each channel to compute HDEEG topographies for overnight decline in SWA between the first and last hour of N2-N3 sleep in each subject. We used Statistical Parametric Mapping (SPM) for statistical analysis to compute correlation between interictal spike frequency and SWA decline, using random effects approach to take into account inter-subject variability. We also assessed for a differential topographical effect of left-sided versus right-sided interictal spikes. Results were corrected for multiple comparisons using SPM family wise error family-wise-error (FWE)-corrected p value < 0.05.
Results:
Random effects analysis revealed a significant negative correlation between the overall spike frequency overnight and SWA decline in central electrodes (peak-level FWE, p< 0.05). No significant difference the topography of SWA decline was found for left-sided versus right sided frequency.
Conclusion:
These results confirm that frequent interictal epileptiform discharges (IED) during sleep are associated with reduced overnight SWA decline, suggesting negative consequences of interictal spikes on cortical excitability and synaptic plasticity. Future studies will investigate correlation between spike frequency and changes in HDEEG topographies of power in other frequency bands and of individual slow wave characteristics.
Funding:
:Tiny blue dot foundation and Lily's fund for epilepsy research