Acoustic enhancement of sleep slow oscillations in mild cognitive impairment.

OBJECTIVE: Slow-wave activity (SWA) during sleep is reduced in people with amnestic mild cognitive impairment (aMCI) and is related to sleep-dependent memory consolidation. Acoustic stimulation of slow oscillations has proven effective in enhancing SWA and memory in younger and older adults. In this study we aimed to determine whether acoustic stimulation during sleep boosts SWA and improves memory performance in people with aMCI. METHODS: Nine adults with aMCI (72 ± 8.7 years) completed one night of acoustic stimulation (stim) and one night of sham stimulation (sham) in a blinded, randomized crossover study. Acoustic stimuli were delivered phase-locked to the upstate of the endogenous sleep slow-waves. Participants completed a declarative recall task with 44 word-pairs before and after sleep. RESULTS: During intervals of acoustic stimulation, SWA increased by >10% over sham intervals (P < 0.01), but memory recall increased in only five of the nine patients. The increase in SWA with stimulation was associated with improved morning word recall (r = 0.78, P = 0.012). INTERPRETATION: Acoustic stimulation delivered during slow-wave sleep over one night was effective for enhancing SWA in individuals with aMCI. Given established relationships between SWA and memory, a larger or more prolonged enhancement may be needed to consistently improve memory in aMCI.

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep.

Introduction: Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Aims: Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Methods: Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results: Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p < .001). When overnight improvement of memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality. Conclusions: We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.

Effects of phase-locked acoustic stimulation during a nap on EEG spectra and declarative memory consolidation.

OBJECTIVES: Acoustic stimulation synchronized to slow waves (SWs) can enhance these sleep features and facilitate memory consolidation during nocturnal sleep. Here, we investigated whether a similar benefit could be accrued following stimulation during an afternoon nap. We also evaluated the event-related dynamics of associated EEG spectral changes and their correlation with memory performance. METHODS: Sixteen healthy young adults (mean age: 22 ± 1.4 years; nine males) were studied under two conditions: stimulation (STIM) and no stimulation (SHAM), in counter-balanced order. In the STIM condition, acoustic stimulation was delivered using blocks of five tones, each phase-locked to the SW up-state during a 90-min nap opportunity. In the SHAM condition, these time points were marked, but tones were not presented. Prior to the nap, participants learned 40 semantically related word pairs and immediate recall was tested. A delayed recall test was administered 45 min after awakening. RESULTS: Compared to the SHAM condition, acoustic stimulation increased SW amplitude, theta, and fast spindle activity and attenuated the forgetting of word pairs (p values < 0.05). CONCLUSION: Phase-locked acoustic stimulation can promote sleep-dependent declarative memory during a daytime nap. This can be achieved by stimulation in Stage 2 and SWS without a requirement for high-amplitude slow wave detection.

Phase-locked loop for precisely timed acoustic stimulation during sleep.

BACKGROUND: A brain-computer interface could potentially enhance the various benefits of sleep. NEW METHOD: We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a phase-locked loop (PLL). RESULTS: The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep. COMPARISON WITH EXISTING METHODS: Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time. CONCLUSIONS: By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function.