02 in ninth individual, Figure 8B). Thus, despite the probabilistic nature of activity onsets in slow waves, the underlying process is not entirely stochastic and reflects the cumulative drive of afferent synaptic input. By examining simultaneous depth EEG and single-unit recordings in multiple regions of the human brain, we show that ON and OFF periods of spiking activity and corresponding EEG slow waves typically involve a limited number of brain regions. Alectinib order Similarly, sleep spindles are mostly local. In addition, slow waves

have a tendency to propagate from prefrontal cortex to the MTL and hippocampus. We also found that activity onsets in individual waves reflect the afferent synaptic drive to a given region. The main observation reported here is that most sleep slow waves are in fact confined to local regions (i.e., detected in a minority of brain areas). Specifically, in most cases we found that when some brain regions were in an ON state, neurons in other brain regions were completely silent. The unique dataset used here was instrumental in unequivocally establishing this phenomenon, since (1) the large size of the human brain facilitated simultaneous recordings across multiple distant sites, and (2) selleck compound the simultaneous

recording of depth EEG, MUA, and spiking of individual neurons allowed us to establish that differences between depth EEGs in different regions reflect local activities rather than noise. Typically, less than 30% of monitored brain regions were involved in each slow wave event. Although our sampling was mostly limited to medial brain areas, it represented activity in multiple (8–12) regions across lobes and hemispheres, so it is reasonable to infer that

these results can be generalized to the entire brain. When global ON and OFF states were observed, they were associated with large slow Edoxaban waves in scalp recordings, usually during deep sleep early in the night, or with K-complexes throughout the night. Local slow waves tended to co-occur across homotopic prefrontal regions, but not across homotopic regions in the MTL (Figure 4E), supporting the role of callosal pathways in slow wave synchronization and propagation (Amzica and Steriade, 1995a). Medial prefrontal regions including the anterior cingulate and orbitofrontal cortex were among the most involved in slow wave occurrence. The demonstration that slow waves are mostly local shows that examples of isolated slow waves (Mohajerani et al., 2010 and Sirota and Buzsaki, 2005) constitute the rule rather than the exception. It is also consistent with evidence that the intensity of sleep slow waves can vary across brain regions (Finelli et al., 2001), that sleep can be regulated locally (Huber et al., 2004 and Huber et al., 2006), and that multiple local generators could contribute to EEG SWA (Murphy et al., 2009 and Riedner et al., 2007).