Introduction
Converging evidence supports the hypothesis that reduced sleep spindles and spindle-slow oscillation (SO) coordination contribute to cognitive deficits in schizophrenia. Closed-loop auditory stimulation in healthy adults increases sleep spindles and improves declarative memory consolidation. Here we investigated whether closed-loop auditory stimulation also improves sleep-dependent procedural memory consolidation as a first step towards an intervention in schizophrenia.
Methods
Thirteen healthy adults participated in two nap sessions (stimulation or detection only) with polysomnography in a counterbalanced order. Participants were trained on the finger tapping Motor Sequence Task (MST), which measures sleep-dependent motor procedural memory consolidation, prior to napping and were tested after awakening. We detected the negative peak of SOs during non-REM sleep and, in the stimulation condition, delivered 50ms of pink noise during the SO up-state.
Results
Auditory stimulation increased SOs and spindles during the SO up-state in a frontocentral cluster of electrodes 800-1200ms after stimulation compared to detection only (p<0.05). Stimulation also showed promise for improving memory consolidation (33% increase in MST overnap improvement from detection-only) but this did not reach significance in this small sample and data collection is ongoing.
Conclusion
Auditory stimulation evoked coordinated spindle-SO events that mediate memory consolidation, but more subjects are needed to evaluate whether it also improves memory. If it does, we will test the effects of stimulation on sleep-dependent memory deficits in patients with schizophrenia. Closed-loop auditory stimulation shows promise as a safe, scalable intervention for cognitive deficits that can be implemented at home with commercially available devices.
Support
R01 MH67720 (DSM & RS), NIH-NHLBI 5T32HL007901-17 (BB), K24MH099421 (DSM), and Simons Foundation (DSM).
Study Objectives
Healthy aging and many disorders show reduced sleep-dependent memory consolidation and corresponding alterations in non-rapid eye movement sleep oscillations. Yet sleep physiology remains a relatively neglected target for improving memory. We evaluated the effects of closed-loop auditory stimulation during sleep (CLASS) on slow oscillations (SOs), sleep spindles, and their coupling, all in relation to motor procedural memory consolidation.
Methods
Twenty healthy young adults had two afternoon naps: one with auditory stimulation during SO upstates and another with no stimulation. Twelve returned for a third nap with stimulation at variable times in relation to SO upstates. In all sessions, participants trained on the Motor Sequence Task prior to napping and were tested afterwards.
Results
Relative to epochs with no stimulation, upstate stimuli disrupted sleep and evoked SOs, spindles, and SO-coupled spindles. Stimuli that successfully evoked oscillations were delivered closer to the peak of the SO upstate and when spindle power was lower than stimuli that failed to evoke oscillations. Across conditions, participants showed similar significant post-nap performance improvement that correlated with the density of SO-coupled spindles.
Conclusions
Despite its strong effects on sleep physiology, CLASS failed to enhance motor procedural memory. Our findings suggest methods to overcome this failure, including better sound calibration to preserve sleep continuity and the use of real-time predictive algorithms to more precisely target SO upstates and to avoid disrupting endogenous SO-coupled spindles and their mnemonic function. They motivate continued development of CLASS as an intervention to manipulate sleep oscillatory dynamics and improve memory.
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