Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

Benchmarking Real-Time Algorithms for In-Phase Auditory Stimulation of Low Amplitude Slow Waves With Wearable EEG Devices During Sleep.

OBJECTIVE: In-phase stimulation of EEG slow waves (SW) during deep sleep has shown to improve cognitive function. SW enhancement is particularly desirable in subjects with low-amplitude SW such as older adults or patients suffering from neurodegeneration. However, existing algorithms to estimate the up-phase of EEG suffer from a poor phase accuracy at low amplitudes and when SW frequencies are not constant. METHODS: We introduce two novel algorithms for real-time EEG phase estimation on autonomous wearable devices, a phase-locked loop (PLL) and, for the first time, a phase vocoder (PV). We compared these phase tracking algorithms with a simple amplitude threshold approach. The optimized algorithms were benchmarked for phase accuracy, the capacity to estimate phase at SW amplitudes between 20 and 60 µV, and SW frequencies above 1 Hz on 324 home-based recordings from healthy older adults and Parkinson disease (PD) patients. Furthermore, the algorithms were implemented on a wearable device and the computational efficiency and the performance was evaluated in simulation and with a PD patient. RESULTS: All three algorithms delivered more than 70% of the stimulation triggers during the SW up-phase. The PV showed the highest capacity on targeting low-amplitude SW and SW with frequencies above 1 Hz. The hardware testing revealed that both PV and PLL have marginal impact on microcontroller load, while the efficiency of the PV was 4% lower. Active stimulation did not influence the phase tracking. CONCLUSION: This work demonstrated that phase-accurate auditory stimulation can also be delivered during fully remote sleep interventions in populations with low-amplitude SW.

Boosting Recovery During Sleep by Means of Auditory Stimulation.

Sufficient recovery during sleep is the basis of physical and psychological well-being. Understanding the physiological mechanisms underlying this restorative function is essential for developing novel approaches to promote recovery during sleep. Phase-targeted auditory stimulation (PTAS) is an increasingly popular technique for boosting the key electrophysiological marker of recovery during sleep, slow-wave activity (SWA, 1-4 Hz EEG power). However, it is unknown whether PTAS induces physiological sleep. In this study, we demonstrate that, when applied during deep sleep, PTAS accelerates SWA decline across the night which is associated with an overnight improvement in attentional performance. Thus, we provide evidence that PTAS enhances physiological sleep and demonstrate under which conditions this occurs most efficiently. These findings will be important for future translation into clinical populations suffering from insufficient recovery during sleep.

Neuromodulation by means of phase-locked auditory stimulation affects key marker of excitability and connectivity during sleep.

The propagating pattern of sleep slow waves (high-amplitude oscillations < 4.5 Hz) serves as a blueprint of cortical excitability and brain connectivity. Phase-locked auditory stimulation is a promising tool for the modulation of ongoing brain activity during sleep; however, its underlying mechanisms remain unknown. Here, eighteen healthy young adults were measured with high-density electroencephalography in three experimental conditions; one with no stimulation, one with up- and one with down-phase stimulation; ten participants were included in the analysis. We show that up-phase auditory stimulation on a right prefrontal area locally enhances cortical involvement and promotes traveling by increasing the propagating distance and duration of targeted small-amplitude waves. On the contrary, down-phase stimulation proves more efficient at perturbing large-amplitude waves and interferes with ongoing traveling by disengaging cortical regions and interrupting high synchronicity in the target area as indicated by increased traveling speed. These results point out different underlying mechanisms mediating the effects of up- and down-phase stimulation and highlight the strength of traveling wave analysis as a sensitive and informative method for the study of connectivity and cortical excitability alterations.