Fragments of wake-like activity frame down-states of sleep slow oscillations in humans: new vistas for studying homeostatic processes during sleep.

During NREM sleep cortical activity corresponding to EEG fast rhythms (FRs>10 Hz) is interrupted by fragments of neural stillness (down-states), responsible for the negative peak within sleep slow oscillation (SSO). Researchers still debate whether the down-states spontaneously occur or need an initial overshoot in fluctuating activity. Herein, we studied temporally-isolated SSO in healthy subjects in order to identify two distinct EEG markers defining a putative initial up-state: i) a significant positive deflection and ii) an associated FR increase, before the negative peak. We found a positive bump preceding the down-state, which is detectable already at the cortical SSO origin site, both during N2 and N3. This early positive deflection, concurrent with a broadband activation, is characterized by an increase of sigma activity (12-18 Hz) from N2 to N3, while an opposite trend was observed for sigma activity crowning the up-state following the negative peak. Also, we found: (i) FR activations during up-states up to high gamma frequencies; (ii) depressed sigma activity in after-spindle recovery phase; and (iii) tightly coordinated activities between distinct bands (12-36 Hz, ~70 Hz, ~85 Hz and 105-125 Hz). The correlation between different bands suggested a common mechanism for sigma and gamma, and the pre-down-state activation associated with the initial bump suggested an activity ignition for down-state, whose intensity is dependent on sleep stage. In conclusion, we hypothesize that FR accompanying SSO could mark i) sleep homeostatic processes, such as the regulation/stabilization of sleep, counterbalancing the detrimental effects of continuous inputs from peripheries, and ii) neural mechanisms favoring the storage of information acquired during wakefulness.