Timing matters: open-loop stimulation does not improve overnight consolidation of word pairs in humans.

The application of auditory clicks during non-rapid eye movement (NREM) sleep phase-locked to the up state of the slow oscillation (closed-loop stimulation) has previously been shown to enhance the consolidation of declarative memories. We designed and applied sequences of three clicks during deep NREM sleep to achieve a quasi-phase-dependent open-loop stimulation. This stimulation was successful in eliciting slow oscillation power in the stimulation period. Although fast and slow spindle power were markedly decreased during the stimulation period, memory consolidation did not differ from control. During putative up states fast spindle power remained, however, at control levels. We conclude that concurrence of slow oscillations and fast spindles suffices to maintain memory consolidation at control levels despite an overall decreased spindle activity.