Interrelations and functional roles of key oscillatory activities during daytime sleep in older adults.

Certain neurophysiological characteristics of sleep, in particular slow oscillations (SOs), sleep spindles, and their temporal coupling, have been well characterised and associated with human memory abilities. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SOs, and their interaction with spindles have only recently been found to play a critical role in memory processing of rodents, through a competitive interaction between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta wave interactions with spindles and SOs, as well as their functional role for memory are still lacking. Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta-spindle coupling and the interplay between delta- and SO-related activity. Additionally, we determined intra-individual stability of coupling measures and their potential link to the ability to form novel memories in a verbal memory task. Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found no evidence for an opposing dependency between SO- and delta-related activities during non-rapid eye movement sleep. Moreover, the ratio between SO- and delta-nested spindles rather than SO-spindle and delta-spindle coupling measures by themselves predicted the ability to form novel memories best. In conclusion, our results do not confirm previous findings in rodents on competitive interactions between delta activity and SO-spindle coupling in older adults. However, they support the hypothesis that SO, delta wave, and spindle activity should be jointly considered when aiming to link sleep physiology and memory formation.

Towards Optimization of Oscillatory Stimulation During Sleep.

BACKGROUND: Oscillatory rhythms during sleep, such as slow oscillations (SOs) and spindles and, most importantly, their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation; however, effects varied quite markedly between individuals, studies, and species. In this study, we aimed to determine how precisely the frequency of stimulation must match the naturally occurring SO frequency in individuals to best improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes. MATERIALS AND METHODS: We addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while stimulation train durations were systematically varied between 30 seconds, 2 minutes, and 5 minutes. RESULTS: Stimulation trains as short as 30 seconds were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects regarding SO-spindle coupling than individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated. CONCLUSIONS: In sum, short stimulation trains were sufficient to induce significant changes in sleep physiology, allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. Regarding individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation, to calibrate stimulation frequency to the SO frequency at the time of stimulation onset. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04714879.

Spatiotemporal Patterns of Adaptation-Induced Slow Oscillations in a Whole-Brain Model of Slow-Wave Sleep.

During slow-wave sleep, the brain is in a self-organized regime in which slow oscillations (SOs) between up- and down-states travel across the cortex. While an isolated piece of cortex can produce SOs, the brain-wide propagation of these oscillations are thought to be mediated by the long-range axonal connections. We address the mechanism of how SOs emerge and recruit large parts of the brain using a whole-brain model constructed from empirical connectivity data in which SOs are induced independently in each brain area by a local adaptation mechanism. Using an evolutionary optimization approach, good fits to human resting-state fMRI data and sleep EEG data are found at values of the adaptation strength close to a bifurcation where the model produces a balance between local and global SOs with realistic spatiotemporal statistics. Local oscillations are more frequent, last shorter, and have a lower amplitude. Global oscillations spread as waves of silence across the undirected brain graph, traveling from anterior to posterior regions. These traveling waves are caused by heterogeneities in the brain network in which the connection strengths between brain areas determine which areas transition to a down-state first, and thus initiate traveling waves across the cortex. Our results demonstrate the utility of whole-brain models for explaining the origin of large-scale cortical oscillations and how they are shaped by the connectome.