This result is in line with the finding that local waves were usually low amplitude, and low-amplitude waves typically occur in late NREM sleep when homeostatic sleep pressure has largely dissipated (Riedner et al., 2007). By contrast, K-complexes were mostly global and stereotypical throughout the night—that is, they did not show significant changes between early and late sleep (Figure 6B; involvement

of 54.8% ± 4.4% in early sleep versus 52.5% ± 1.9% in late sleep; p = 0.98). Interestingly, sleep spindles became slightly less local in late sleep, as sleep pressure dissipated (Figure 6C; involvement Selleck Cilengitide of 44.2% ± 0.6% in early sleep versus 47.1% ± 0.5% in late sleep; p < 0.00014). This result once again supports the notion that local sleep spindles cannot be simply explained by an association with local slow waves. To examine whether slow waves propagate along typical

pathways, we checked for consistent temporal delays between brain regions in which the same wave was observed. Figure 7A provides an example of mean slow waves in depth EEG of different brain structures in one individual, revealing a propagation trend from medial frontal cortex to the MTL and hippocampus. This propagation was evident also when examining the distribution of lags for individual waves (Figure 7A, right). Despite variability in the timings Selleckchem Ulixertinib of individual waves, some regions consistently preceded scalp EEG whereas others followed it. A systematic analysis of depth EEG established that slow waves had a strong propensity to propagate from medial frontal cortex to the MTL and hippocampus. Specifically, we identified all slow waves that were detected

within ±400 ms across several brain structures (Experimental Procedures). Sorting regions according second to the order in which their slow waves were detected revealed a clear tendency of slow waves to propagate from medial frontal cortex to the MTL (Figure 7B), which was highly significant statistically (Figure 7C; p < 2.3 × 10−8, unequal variance t test). In addition, this propagation tendency was consistent across individual subjects and robust to different examinations (Figure S6). Figure 7D shows an example of individual slow waves propagating across multiple brain structures. As can be seen, time offsets in OFF periods in different brain regions followed a propagation from frontal cortex to the MTL (diagonal green lines). Next, slow wave propagation was quantitatively examined in unit discharges in all 11 individuals in whom unit recordings were obtained simultaneously in frontal and MTL regions. Mean spiking activities underlying slow waves in medial frontal cortex versus MTL revealed a robust time offset (Figure 7E, left). Across individual neurons, minimal firing in frontal neurons (n = 76) was −85 ± 22 ms relative to scalp Fz negative peak, whereas minimal firing in MTL neurons (n = 155) was +102 ± 20 ms relative to the same time reference, indicating an average difference of 187 ms (Figure 7E, right).