Sleep and cardiac autonomic modulation in older adults: Insights from an at-home study with auditory deep sleep stimulation.

The autonomic nervous system regulates cardiovascular activity during sleep, likely impacting cardiovascular health. Aging, a primary cardiovascular risk factor, is associated with cardiac autonomic disbalance and diminished sleep slow waves. Therefore, slow waves may be linked to aging, autonomic activity and cardiovascular health. However, it is unclear how sleep and slow waves are linked to cardiac autonomic profiles across multiple nights in older adults. We conducted a randomized, crossover trial involving healthy adults aged 62-78 years. Across 2 weeks, we applied auditory stimulation to enhance slow waves and compared it with a SHAM period. We measured sleep parameters using polysomnography and derived heart rate, heart rate variability approximating parasympathetic activity, and blood pulse wave approximating sympathetic activity from a wearable. Here, we report the results of 14 out of 33 enrolled participants, and show that heart rate, heart rate variability and blood pulse wave within sleep stages differ between the first and second half of sleep. Furthermore, baseline slow-wave activity was related to cardiac autonomic activity profiles during sleep. Moreover, we found auditory stimulation to reduce heart rate variability, while heart rate and blood pulse wave remained unchanged. Lastly, within subjects, higher heart rate coincided with increased slow-wave activity, indicating enhanced autonomic activation when slow waves are pronounced. Our study shows the potential of cardiac autonomic markers to offer insights into participants' baseline slow-wave activity when recorded over multiple nights. Furthermore, we highlight that averaging cardiac autonomic parameters across a night may potentially mask dynamic effects of auditory stimulation, potentially playing a role in maintaining a healthy cardiovascular system.

Exploring the local field potential signal from the subthalamic nucleus for phase-targeted auditory stimulation in Parkinson's disease.

BACKGROUND: Enhancing slow waves, the electrophysiological (EEG) manifestation of non-rapid eye movement (NREM) sleep, could potentially benefit patients with Parkinson's disease (PD) by improving sleep quality and slowing disease progression. Phase-targeted auditory stimulation (PTAS) is an approach to enhance slow waves, which are detected in real-time in the surface EEG signal. OBJECTIVE: We aimed to test whether the local-field potential of the subthalamic nucleus (STN-LFP) can be used to detect frontal slow waves and assess the electrophysiological changes related to PTAS. METHODS: We recruited patients diagnosed with PD and undergoing Percept™ PC neurostimulator (Medtronic) implantation for deep brain stimulation of STN (STN-DBS) in a two-step surgery. Patients underwent three full-night recordings, including one between-surgeries recording and two during rehabilitation, one with DBS+ (on) and one with DBS- (off). Surface EEG and STN-LFP signals from Percept PC were recorded simultaneously, and PTAS was applied during sleep in all three recording sessions. RESULTS: Our results show that during NREM sleep, slow waves of the cortex and STN are time-locked. PTAS application resulted in power and coherence changes, which can be detected in STN-LFP. CONCLUSION: Our findings suggest the feasibility of implementing PTAS using solely STN-LFP signal for slow wave detection, thus without a need for an external EEG device alongside the implanted neurostimulator. Moreover, we propose options for more efficient STN-LFP signal preprocessing, including different referencing and filtering to enhance the reliability of cortical slow wave detection in STN-LFP recordings.

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics.

Slow waves, the hallmark feature of deep nonrapid eye movement sleep, do potentially drive restorative effects of sleep on brain and body functions. Sleep modulation techniques to elucidate the functional role of slow waves thus have gained large interest. Auditory slow wave stimulation is a promising tool; however, directly comparing auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included nights and found a large and global increase in slow-wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow-wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA, and thus, our findings provide insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow-wave enhancements translates into a more rested cardiovascular system on a subsequent day.

Auditory deep sleep stimulation in older adults at home: a randomized crossover trial.

Background: Auditory stimulation has emerged as a promising tool to enhance non-invasively sleep slow waves, deep sleep brain oscillations that are tightly linked to sleep restoration and are diminished with age. While auditory stimulation showed a beneficial effect in lab-based studies, it remains unclear whether this stimulation approach could translate to real-life settings. Methods: We present a fully remote, randomized, cross-over trial in healthy adults aged 62-78 years (clinicaltrials.gov: NCT03420677). We assessed slow wave activity as the primary outcome and sleep architecture and daily functions, e.g., vigilance and mood as secondary outcomes, after a two-week mobile auditory slow wave stimulation period and a two-week Sham period, interleaved with a two-week washout period. Participants were randomized in terms of which intervention condition will take place first using a blocked design to guarantee balance. Participants and experimenters performing the assessments were blinded to the condition. Results: Out of 33 enrolled and screened participants, we report data of 16 participants that received identical intervention. We demonstrate a robust and significant enhancement of slow wave activity on the group-level based on two different auditory stimulation approaches with minor effects on sleep architecture and daily functions. We further highlight the existence of pronounced inter- and intra-individual differences in the slow wave response to auditory stimulation and establish predictions thereof. Conclusions: While slow wave enhancement in healthy older adults is possible in fully remote settings, pronounced inter-individual differences in the response to auditory stimulation exist. Novel personalization solutions are needed to address these differences and our findings will guide future designs to effectively deliver auditory sleep stimulations using wearable technology.

The Potential Role of Sleep in Promoting a Healthy Body Composition: Underlying Mechanisms Determining Muscle, Fat, and Bone Mass and Their Association with Sleep.

Sleep plays an essential role in human life. While sleep is a state elicited by the brain, its vital role reaches beyond maintaining brain health. Unhealthy sleeping habits have been associated with increased risk for inflammation, obesity, or diabetes. Evidence is emerging that sleep guides processes playing an important role in promoting the regulation of endocrine function involved in tissue regeneration and tissue remodelling. Thereby, sleep presumably is a critical factor contributing to the balance of core body tissues: bone, fat, and muscle mass. Given the increasing prevalence of various chronic diseases and comorbidities due to unhealthy lifestyle choices, sleep could be a key target to promote a healthy body composition up until old age. Here, we review the potential role of sleep and its underlying brain oscillations in body core tissues turnover. Specifically, we discuss potential underlying mechanisms linking sleep to body composition, both during rest and under challenging conditions. Among other described pathways, we highlight the possible role of the growth hormone that was found to be involved in the homeostasis of all core body tissues and has been strongly linked to brain activity dominating deep sleep, the so-called slow waves. Finally, we formulate important questions to be addressed in future research on the effect of sleep on body composition and specifically emphasize the importance of intervention studies to move from correlative to causal evidence.