Biometrics from a Wearable Device Reveals Temporary Effects of COVID-19 Vaccines on Cardiovascular, Respiratory, and Sleep Physiology

Although vaccines against SARS-CoV-2 have been proven safe and effective, transient side-effects lasting 24-48 hours post-vaccination have been reported. To better understand the subjective and objective response to COVID-19 vaccination, we conducted a retrospective analysis on 69619 subscribers to a wrist-worn biometric device (WHOOP Inc, Boston, MA, USA) who received either the AstraZeneca, Janssen/Johnson & Johnson, Moderna, or Pfizer/BioNTech vaccine. The WHOOP device measures resting heart rate (RHR), heart rate variability (HRV), respiratory rate (RR), and sleep architecture, and these physiological measures were normalized to the same day of the week, one week prior to vaccination. Averaging across vaccines, RHR, RR, and percent sleep derived from light sleep were elevated on the first night following vaccination and returned to baseline within four nights post-vaccination. When statistical differences were observed between doses on the first night post-vaccination, larger deviations in physiological measures were observed following the first dose of AstraZeneca and the second dose of Moderna and Pfizer/BioNTech. When statistical differences were observed between age groups or gender on the first night post-vaccination, larger deviations in physiological measures were observed in younger populations and in females (compared to males). When combining self-reported symptoms (fatigue, muscle aches, headache, chills, or fever) with the objectively measured physiological parameters, we found that self-reporting fever or chills had the strongest association with deviations in physiological measures following vaccination. In summary, these results suggest that COVID-19 vaccines temporarily affect cardiovascular, respiratory, and sleep physiology, and that dose, gender, and age affect the physiological response to vaccination.

Cardiopulmonary Sleep Spectrograms Open a Novel Window Into Sleep Biology—Implications for Health and Disease

The interactions of heart rate variability and respiratory rate and tidal volume fluctuations provide key information about normal and abnormal sleep. A set of metrics can be computed by analysis of coupling and coherence of these signals, cardiopulmonary coupling (CPC). There are several forms of CPC, which may provide information about normal sleep physiology, and pathological sleep states ranging from insomnia to sleep apnea and hypertension. As CPC may be computed from reduced or limited signals such as the electrocardiogram or photoplethysmogram (PPG) vs. full polysomnography, wide application including in wearable and non-contact devices is possible. When computed from PPG, which may be acquired from oximetry alone, an automated apnea hypopnea index derived from CPC-oximetry can be calculated. Sleep profiling using CPC demonstrates the impact of stable and unstable sleep on insomnia (exaggerated variability), hypertension (unstable sleep as risk factor), improved glucose handling (associated with stable sleep), drug effects (benzodiazepines increase sleep stability), sleep apnea phenotypes (obstructive vs. central sleep apnea), sleep fragmentations due to psychiatric disorders (increased unstable sleep in depression).

Paradoxical excitation of lateral habenula neurons by propofol involves enhanced presynaptic release of glutamate

Sleep is a fundamental physiological process conserved across most species. As such, deficits in sleep can result in a myriad of psychological and physical health issues. However, the mechanisms underlying the induction of sleep are relatively unknown. Interestingly, general anesthetics cause unconsciousness by positively modulating GABA-A receptors (GABAARs). Based on this observation, it is hypothesized that GABAARs play a critical role in modulating circuits involved in sleep to promote unconsciousness. Recently, the lateral habenula (LHb) has been demonstrated to play a role in sleep physiology and sedation. Specifically, propofol has been shown to excite LHb neurons to promote sedation. However, the mechanism by which this occurs is unknown. Here, we utilize whole-cell voltage and current clamp recordings from LHb neurons obtained from 8-10 week old male mice to determine the physiological mechanisms for this phenomenon. We show that bath application of 1.5μM propofol is sufficient to increase LHb neuronal excitability involving synaptic transmission, but not through modulation of intrinsic properties. Additionally, although there is increased LHb neuronal excitability, GABAARs localized postsynaptically on LHb neurons are still responsive to propofol, as indicated by an increase in the decay time. Lastly, we find that propofol increases the synaptic drive onto LHb neurons involving enhanced presynaptic release of both glutamate and GABA. However, the greatest contributor to the potentiated synaptic drive is the increased release of glutamate which shifts the balance of synaptic transmission towards greater excitation. Taken together, this study is the first to identify the physiological basis for why LHb neurons are excited by propofol, rather than inhibited, and as a result promote sedation.

Measurement of Sleep Behaviors in Chromosome 15q11.2-13.1 Duplication (Dup15q Syndrome)

Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children's Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome.

Towards optimization of oscillatory stimulation during sleep

Background: Oscillatory rhythms during sleep such as slow oscillations (SO) 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. Objective: Here, we aimed to determine how precisely the frequency of stimulation has to match the naturally occurring SO frequency in individuals to optimally improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes. Methods: We addressed these questions by comparing so-tDCS with individually adapted SO frequency to standardized frequency of 0.75Hz in a cross-over design with 28 healthy older participants during napping while systematically varying stimulation train durations between 30s, 2min and 5min. Results: Stimulation trains as short as 30s were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects with regard to SO-spindle coupling in comparison to individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated. Conclusion: 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 effects in future studies. With regard to 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 time of stimulation onset.

Sleep in the Intensive Care Unit through the Lens of Breathing and Heart Rate Variability: A Cross-Sectional Study

Background. Full polysomnography, the gold standard of sleep measurement, is impractical for widespread use in the intensive care unit (ICU). Wrist-worn actigraphy and subjective sleep assessments do not measure sleep physiology adequately. Here, we explore the feasibility of estimating conventional sleep indices in the ICU with heart rate variability (HRV) and respiration signals using artificial intelligence methods. Methods. We used deep learning models to stage sleep with HRV (through electrocardiogram) and respiratory effort (through a wearable belt) signals in critically ill adult patients admitted to surgical and medical ICUs, and in covariate-matched sleep laboratory patients. We analyzed the agreement of the determined sleep stages between the HRV- and breathing-based models, computed sleep indices, and quantified breathing variables during sleep. Results. We studied 102 adult patients in the ICU across multiple days and nights, and 220 patients in a clinical sleep laboratory. We found that sleep stages predicted by HRV- and breathing-based models showed agreement in 60% of the ICU data and in 81% of the sleep laboratory data. In the ICU, deep NREM (N2 + N3) proportion of total sleep duration was reduced (ICU 39%, sleep laboratory 57%, p<0.01), REM proportion showed heavy-tailed distribution, and the number of wake transitions per hour of sleep (median = 3.6) was comparable to sleep laboratory patients with sleep-disordered breathing (median = 3.9). Sleep in the ICU was also fragmented, with 38% of sleep occurring during daytime hours. Finally, patients in the ICU showed faster and less variable breathing patterns compared to sleep laboratory patients. Conclusions. Cardiovascular and respiratory signals encode sleep state information, which can be utilized to measure sleep state in the ICU. Using these easily measurable variables can provide automated information about sleep in the ICU.

Neurophysiology of Basic Molecules Affecting Sleep and Wakefulness Mechanisms, Fundamentals of Sleep Pharmacology

As part of the biological rhythm, the human brain has a healthy functioning with the ability to differentiate between day and night hours in any given day (sleep rhythm, life rhythm). From the control of hormone levels to muscle tonus, from the regulation of respiratory rate to the content of our thoughts, sleep has an impact on all bodily and cognitive functions. It is not surprising to see such effects of sleep on the body as it leads to significant changes in the electrical activity of the brain in general. Electrical signal changes in the brain (sleep-wakefulness rhythm) are regulated by neurohormonal molecules and their receptors in the body. Neurotransmitters that control sleep and wakefulness can be listed as “Glutamate, Acetylcholine, Histamine, Norepinephrine and GABA”. Main hormones are: Melatonin, Corticotropin Releasing Hormone (CRH), cortisol, prolactin, Growth Hormone (GH), Insulin like Growth Factor (IGF-1, Somatomedin-C), Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), progesterone, estrogen, testosterone, catecholamines, leptin and neuropeptide Y″. The effects of pharmacological agents on sleep and wakefulness cycles are materialized through the following molecules and their receptors: Hypnotics (GABA A agonists, benzodiazepines, gabapentin, tiagabine), sedative antidepressants (tricyclic antidepressants, trazadone, mitrazapine), antihistamines, medications used for the treatment of sleeplessness (melatonin and melatonin analogues), amphetamine (most commonly used stimulant), secretion of monoamines (dopamine), non-amphetamine stimulants used in the treatment of hypersomnia and narcolepsy (modafinil, bupropion, selegiline, caffeine) and other substances (alcohol, nicotine, anesthetics). To the extent we can conceptualize the physiological mechanisms of these basic molecules listed above and the regions they affect, we can appreciate the effects of these substances on sleep physiology and sleep disorders.

Interrelations between delta waves, spindles and slow oscillations in human NREM sleep and their functional role in memory

Certain neurophysiological characteristics of sleep, in particular slow oscillations (SO), sleep spindles, and their temporal coupling, have been well characterized and associated with human memory formation. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SO, have only recently been found to play a critical role in memory processing of rodents, through a competitive interplay between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta waves, their 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. Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found that increased delta activity was accompanied by stronger SO-spindle coupling. Moreover, we identified the ratio between SO- and delta-nested spindles as the sleep parameter that predicted ability to form novel memories best. Our study suggests that SOs, delta waves and sleep spindles should be jointly considered when aiming to link sleep physiology and memory formation in aging.

Cronobiological and Sleep Related Aspects Associated to Neurodevelopment and Academic Performance in Pediatric Age

Biological rhythms and sleep as their main representative are relevant biofunctional factors to the neuro-cognitive and behavioral development with particular interest in pediatric domain. Some aspects associated to central nervous system and higher function homeostasis, like social-afective equilibrium, critical judgement and memories consolidations and learning, have, in this phase of life, a relationship with the circadian timing system stability and with cronotype. On the other hand, inadequate or insufficient sleep has a negative impact in several biopsychosocial parameters interacting with these domains and conditioning the normal development causing changes in neuro-cognitive and behavioral performance. This review looked for the fundamental aspects of chronobiology and sleep physiology applied to neurodevelopment and its impact in the educational context regarding academic performance.