Regional changes of non-rapid eye movement (NREM) sleep delta and sigma activity, and their temporal coupling have been related to experience-dependent plastic changes during previous wakefulness. These sleep-specific rhythms seem to be important for brain recovery and memory consolidation. Recently, it was demonstrated that by targeting slow waves in a particular region at a specific phase with closed-loop auditory stimulation, it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. In our study, we tested whether closed-loop auditory stimulation targeting the up-phase of slow waves might not only interact with the main sleep rhythms but also with their coupling within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances delta, theta and sigma power, changes in cross-frequency coupling of these oscillations were more spatially restricted. Importantly, a significant increase in delta-sigma coupling was observed over the right parietal area, located directly posterior to the target electrode. These findings suggest that closed-loop auditory stimulation locally modulates coupling between delta phase and sigma power in a targeted region, which could be used to manipulate sleep-dependent neuroplasticity within the brain network of interest. A substantial body of evidence highlights the importance of non-rapid eye movement (NREM) sleep for experience-dependent neuroplasticity and associated improvements in behavioral performance after a bout of sleep 1,2. NREM sleep electroencephalographic (EEG) recordings are hallmarked by neocortical slow waves (1-4 Hz) and sleep spindles, the waxing and waning activity in the sigma frequency band (10-16 Hz). It is well established that slow waves orchestrate faster oscillations, with the up-phase of slow waves being associated with increased sigma band activity, and sigma oscillations, in turn, group gamma activity in their troughs 3,4. This precise crossfrequency phase-amplitude coupling is thought to organize communication across multiple brain areas and to facilitate coordinated information processing in brain networks during NREM sleep 5. Not only the magnitude and spatial distribution of slow waves and sigma activity 3,6-10 , but especially their temporal coupling seems to contribute to sleep-dependent benefits of behavioral performance 11,12. Similar to phase-amplitude coupling between slow waves and sigma, modulation of theta band activity (5-8 Hz) by the phase of slow waves has been described in several studies. Both in surface EEG and in intracranial (iEEG) recordings, theta power was increased during the transition to the down phase of slow waves, with the last trough of theta-burst coinciding with the slow-wave down-phase 5,13-15. Moreover, theta band activity in NREM sleep may play a role in sleep-dependent memory consolidation in humans. NREM theta oscillations were associated with the replay of the wake neuronal activity patterns during slow-wave sleep 16,17. Fur...
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.
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