Cueing memory during sleep is optimal during slow-oscillatory up-states

Slow oscillations play a major role in neural plasticity. It is assumed that slow oscillatory up-states represent crucial time windows for memory reactivation and consolidation during sleep. Here we experimentally tested this assumption by utilizing closed-loop targeted memory reactivation (closed-loop TMR): Healthy participants were re-exposed to prior learned foreign vocabulary during up- and down-states of slow oscillations, respectively, in a within-subject design. We show that presenting memory cues during slow oscillatory up-states robustly improves recall performance, whereas memory cueing during down-states did not result in a clear behavioral benefit. On a neural basis successful memory reactivation during up-states was associated with a characteristic power increase in the theta and sleep spindle band. Such increases were completely absent for down-state memory cues. Our findings provide experimental support for the assumption that slow oscillatory up-states represent privileged time windows for memory reactivation, while the interplay of slow oscillations, theta and sleep spindle activity promote successful memory consolidation during sleep.