The transition from wakefulness to sleep represents the most conspicuous change in behavior and the level of consciousness occurring in the healthy brain. It is accompanied by similarly conspicuous changes in neural dynamics, traditionally exemplified by the change from “desynchronized” electroencephalogram activity in wake to globally synchronized slow wave activity of early sleep. However, unit and local field recordings indicate that the transition is more gradual than it might appear: On one hand, local slow waves already appear during wake; on the other hand, slow sleep waves are only rarely global. Studies with functional magnetic resonance imaging also reveal changes in resting-state functional connectivity (FC) between wake and slow wave sleep. However, it remains unclear how resting-state networks may change during this transition period. Here, we employ large-scale modeling of the human cortico-cortical anatomical connectivity to evaluate changes in resting-state FC when the model “falls asleep” due to the progressive decrease in arousal-promoting neuromodulation. When cholinergic neuromodulation is parametrically decreased, local slow waves appear, while the overall organization of resting-state networks does not change. Furthermore, we show that these local slow waves are structured macroscopically in networks that resemble the resting-state networks. In contrast, when the neuromodulator decrease further to very low levels, slow waves become global and resting-state networks merge into a single undifferentiated, broadly synchronized network.

G.D. was supported by the ERC Advanced Grant: DYSTRUCTURE/n(no. 295129), by the Spanish Research Project/nSAF2010-16085, and by the CONSOLIDER-INGENIO 2010/nProgram CSD2007-00012 and the FP7-ICT BrainScales. G.T./nwas supported by the Paul Allen Family Foundation and by the/nMcDonnell Foundation. P.H. was supported by Leenaards/nFoundation. The research reported herein was supported by/nthe Brain Network Recovery Group through the James/nS. McDonnell Foundation.