All patients showed typical NREM-REM sleep cycles, and some showed homeostatic decline of SWA throughout sleep. These results indicate that sleep measures were in general agreement with typical findings in healthy young adults (e.g., Riedner et al., 2007). Having characterized sleep using standard noninvasive polysomnography, individual

slow waves in NREM sleep were identified Akt activity in the depth EEG of each brain region separately. Although sleep profiles were within the normal range, we further verified that detected waves reflected physiological sleep slow waves rather than epileptic events (Experimental Procedures). Putative slow waves were separated to those preceded (within 1 s) by an interictal spike Ribociclib (“paroxysmal” discharges) versus those unrelated to epilepsy (“physiological” sleep slow waves). The shape of physiological sleep slow waves was symmetrical and significantly different than that of asymmetrical paroxysmal discharges (Figure S2A). Specifically, in

paroxysmal slow waves following interictal spikes, the rise slope was 44% ± 0.07% steeper than the fall slope (n = 129 depth electrodes; p < 7.4 × 10−5, paired t test on rise and fall slopes). In addition, paroxysmal discharges were limited to specific sites in comparison to physiological slow waves, which were detected in all brain structures in all patients. Thus, in many channels, virtually no interictal spikes were observed before slow waves (and nearly all putative slow waves were physiological), while in a few channels many

events were pathological (mean, 14%; why range, 0.06%–46%). By contrast, the number of physiological slow waves was consistent between electrodes, with numbers matching those found in healthy individuals (37.3 ± 0.5 slow waves per minute of NREM sleep), as in (Riedner et al., 2007). Next, isolated unit discharges underlying physiological sleep slow waves were examined. Figure 2 provides an example of EEG and unit activities during global slow waves occurring in unison across multiple brain regions during deep NREM sleep in one individual. Negative peaks in the scalp EEG tightly corresponded to positive peaks of depth EEG in cortical and subcortical structures across different lobes and hemispheres. Locally, extracellular recordings revealed an OFF period where unit spiking activity ceased almost entirely, likely corresponding to the down state of the slow oscillations as recorded intracellularly. As in previous work (Vyazovskiy et al., 2009b), we use the terms “ON” and “OFF” periods, instead of “up” and “down” or “depolarized” and “hyperpolarized” states (Steriade et al.