Insights on auditory closed-loop stimulation targeting sleep spindles in slow oscillation up-states

Background: The consolidation of sleep-dependent memories is mediated by an interplay of cortical slow oscillations (SOs) and thalamo-cortical sleep spindles. Whereas an enhancement of SOs with auditory closed-loop stimulation has been proven highly successful, the feasibility to induce and boost sleep spindles with auditory stimulation remains unknown thus far. New method: Here we tested the possibility to enhance spindle activity during endogenous SOs and thereby to promote memory consolidation. Performing a sleep study in healthy humans, we applied an auditory Spindle stimulation and compared it with an Arrhythmic stimulation and a control condition comprising no stimulation (Sham). Results: With Spindle stimulation we were not able to directly entrain endogenous spindle activity during SO up-states. Instead, both Spindle and Arrhythmic stimulation evoked a resonant SO response accompanied by an increase in spindle power phase-locked to the SO up-state. Assessment of overnight retention of declarative word-pairs revealed no difference between all conditions. Comparison with existing methods: Our Spindle stimulation produced oscillatory evoked responses (i.e., increases in SOs and spindle activity during SO up-states) quite similar to those observed after the auditory closed-loop stimulation of SOs in previous studies, lacking however the beneficial effects on memory retention. Conclusion: Our findings put the endeavour for a selective enhancement of spindle activity via auditory pathways into perspective and reveal central questions with regard to the stimulation efficacy on both an electrophysiological and a neurobehavioral level.