AbstractSlow oscillations and spindle activity during non-rapid eye movement sleep have been implicated in memory consolidation. Closed-loop acoustic stimulation has previously been shown to enhance slow oscillations and spindle activity during sleep and improve verbal associative memory. We assessed the effect of closed-loop acoustic stimulation during a daytime nap on a virtual reality spatial navigation task in 12 healthy human subjects in a randomized within-subject crossover design. We show robust enhancement of slow oscillation and spindle activity during sleep. However, no effects on behavioral performance were observed when comparing real versus sham stimulation. To explore whether memory enhancement effects were task specific and dependent on nocturnal sleep, in a second experiment with 19 healthy subjects, we aimed to replicate a previous study that used closed-loop acoustic stimulation to enhance memory for word pairs. The methods used were as close as possible to those used in the original study, except that we used a double-blind protocol, in which both subject and experimenter were unaware of the test condition. Again, we successfully enhanced slow oscillation and spindle power, but again did not strengthen associative memory performance with stimulation. We conclude that enhancement of sleep oscillations may be insufficient to enhance memory performance in spatial navigation or verbal association tasks, and provide possible explanations for lack of behavioral replication.