Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome

Sleep is the brain state when cortical activity decreases and memory consolidates. However, in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome, sleep is the preferential period when epileptic spike-wave discharges (SWDs) appear, with more severe epileptic symptoms in female patients than male patients, which influencing patient sleep quality and memory. Currently, seizure onset mechanisms during sleep period still remain unknown. Our previous work has shown that the sleep-like state-dependent synaptic potentiation mechanism can trigger epileptic SWDs (Zhang et al., 2021). In this study, using one heterozygous (het) knock-in (KI) transgenic mice (GABAA receptor γ2 subunit Gabrg2Q390X mutation) and an optogenetic method, we hypothesized that slow-wave oscillations (SWOs) themselves in vivo could trigger epileptic seizures. We found that epileptic SWDs in het Gabrg2+/Q390X KI mice exhibited preferential incidence during NREM sleep period, accompanied by motor immobility/ facial myoclonus/vibrissal twitching, with more frequent incidence in female het KI mice than male het KI mice. Optogenetic induced SWOs in vivo significantly increased epileptic seizure incidence in het Gabrg2+/Q390X KI mice with increased duration of NREM sleep or quiet-wakeful states. Furthermore, suppression of SWO-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde (DEAB) injection (i.p.) greatly decreased seizure incidence in het KI mice, suggesting that SWOs did trigger seizure activity in het KI mice. In addition, EEG delta-frequency (0.1-4 Hz) power spectral density during NREM sleep was significantly larger in female het Gabrg2+/Q390X KI mice than male het Gabrg2+/Q390X KI mice, which likely contributes to the gender difference in seizure incidence during NREM sleep/quiet-wake as that in human patients.

Lingering Impacts on Sleep Following the Daylight Savings Time Transition

Background: The “spring forward” change to Daylight Savings Time (DST) has been epidemiologically linked with numerous health and safety risks in the days following the transition, but direct measures of sleep are infrequently collected in community dwelling individuals. Methods: The Project Baseline Health Study (PBHS), a prospective, multicenter, longitudinal representative U.S. cohort study begin in 2017 launched a Sleep Mission in March 2021 to characterize sleep using patient-reported and wearable device measures, in free-living circumstances during the DST switch. Estimated sleep period duration, subjective restedness and quality, and watch metrics were compared before and after the DST transition during specified timeframes. Results: Of the total PBHS population of 2502 participants, 606 participants received an invitation and 419 participants opted in to the Sleep Mission (69.1%). The transition to DST resulted in both acute and lingering impacts on sleep. Acute effects included a 29.6 minute reduction in sleep period (p=0.01) and lower ratings of how well participants slept, as well as reduced next-day restedness. In the week following the time change, a persistent reduction in restedness scores, and a trend towards a decrease in sleeping heart rate variability were observed. Conclusion: The Daylight Savings Time transition is associated with an acute reduction in sleep period, and lingering impacts on self-reported restedness, as well as a trend towards reduced heart rate variability into the week following the transition. This work adds to a growing understanding of the persistence of impacts on sleep health metrics due to the DST transition.

Duty-Cycle-Based Pre-Emption Protocol for Emergency Networks

This paper proposes a new duty-cycle-based protocol for transmitting emergent data with high priority and low latency in a sensor network environment. To reduce power consumption, the duty cycle protocol is divided into a listen section and a sleep section, and data can only be received when the receiving node is in the listen section. In this paper, high-priority transmission preempts low-priority transmission by distinguishing between high-priority preamble and low-priority preamble. However, even when a high priority transmission preempts a low priority transmission such that the high priority transmission is received first, if the sleep period is very long, the delay may be large. To solve this problem, the high priority short preamble and high priority data reduce receiver sensitivity and increase coverage through repeated transmission. If there are several receiving nodes within a wide coverage, the receiving node that wakes up first can receive the transmission, thus reducing the delay. The delay can also be further reduced by alternately reducing the sleep cycle of one node among the receiving nodes that can receive it. This paper shows that emergent data can be transmitted effectively and reliably by reducing the delay of high-priority data to a minimum through the use of preemption, coverage extension, and an asymmetric sleep cycle.

Sleep Characteristics According to Gender and Age Measured by Wrist Actigraphy

The sleep/wake rhythm is one of the most important biological rhythms. Quality and duration of sleep change during lifetime. The aim of our study was to determine differences in sleep efficiency, movement, and fragmentation during sleep period between genders and according to age. Sleep period was monitored by wrist actigraphy under home-based conditions. Seventy-four healthy participants—47 women and 27 men participated in the study. The participants were divided by age into groups younger than 40 years and 40 years and older. Women showed lower sleep fragmentation and mobility during sleep compared to men. Younger women showed a higher actual sleep and sleep efficiency compared to older women and younger men. Younger men compared to older men had a significantly lower actual sleep, lower sleep efficiency and significantly more sleep and wake bouts. Our results confirmed differences in sleep parameters between genders and according to age. The best sleep quality was detected in young women, but gender differences were not apparent in elderly participants, suggesting the impact of sex hormones on sleep.

REM Sleep: An Unknown Indicator of Sleep Quality

Standard polysomnographic analysis of sleep has not provided evidence of an objective measure of sleep quality; however, factors such as sleep duration and sleep efficiency are those more consistently associated with the subjective perception of sleep quality. Sleep reduction as currently occurs in our 24/7 society has had a profound impact on sleep quality; the habitual sleep period should fit within what is a limited nighttime window and may not be sufficient to satisfy the whole sleep process; moreover, the use of artificial light during the evening and early night hours can delay and disturb the circadian rhythms, especially affecting REM sleep. The correct phase relationship of the sleep period with the circadian pacemaker is an important factor to guarantee adequate restorative sleep duration and sleep continuity, thus providing the necessary background for a good night’s sleep. Due to the fact that REM sleep is controlled by the circadian clock, it can provide a window-like mechanism that defines the termination of the sleep period when there is still the necessity to complete the sleep process (not only wake-related homeostasis) and to meet the circadian end of sleep timing. An adequate amount of REM sleep appears necessary to guarantee sleep continuity, while periodically activating the brain and preparing it for the return to consciousness.

Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions

Aims/hypothesis Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual’s sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning. Methods Healthy adults’ data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals). Results Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (pinteraction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p < 0.03). Later sleep midpoint (time deviation from midnight) was found to be significantly associated with higher postprandial glucose, in both between-person and within-person comparisons (p = 0.035 and p = 0.051, respectively). Conclusions/interpretation Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person’s deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registrationClinicalTrials.gov NCT03479866. Graphical abstract

Decreased nocturnal heart rate variability and potentially related brain regions in arteriosclerotic cerebral small vessel disease

Background To assess heart rate variability (HRV) among patients with arteriosclerotic cerebral small vessel disease (CSVD) by comparing with control subjects, and to determine whether HRV parameters were related to structural alterations in brain regions involved in autonomic regulation among CSVD patients. Methods We consecutively recruited subjects aged between 50 and 80 years who visited the Stroke Prevention Clinic of our hospital and have completed brain magnetic resonance imaging examination from September 1, 2018 to August 31, 2019. Polysomnography and synchronous analyses of HRV were then performed in all participants. Multivariable binary logistic regression was used to identify the relationship between HRV parameters and CSVD. Participants were invited to further undergo three-dimensional brain volume scan, and the voxel based morphometry (VBM) analysis was used to identify gray matter atrophy. Results Among 109 participants enrolled in this study, 63 were assigned to the arteriosclerotic CSVD group and 46 to the control group. Lower standard deviation of normal-to-normal intervals (SDNN, OR = 0.943, 95% CI 0.903 to 0.985, P = 0.009) and higher ratio of low to high frequency power (LF/HF, OR = 4.372, 95% CI 1.033 to 18.508, P = 0.045) during the sleep period were associated with CSVD, independent of traditional cerebrovascular risk factors and sleep disordered breathing. A number of 24 CSVD patients and 21 controls further underwent three-dimensional brain volume scan and VBM analysis. Based on VBM results, SDNN during the awake time (β = 0.544, 95% CI 0.211 to 0.877, P = 0.001) and the sleep period (β = 0.532, 95% CI 0.202 to 0.862, P = 0.001) were both positively related with gray matter volume within the right inferior frontal gyrus only among CSVD patients. Conclusions Decreased nocturnal HRV is associated with arteriosclerotic CSVD independent of traditional cerebrovascular risk factors and sleep disordered breathing. The structural atrophy of some brain regions associated with cardiac autonomic regulation sheds light on the potential relationship. Trial registration Trial registration number: ChiCTR1800017902. Date of registration: 20 Aug 2018.

The Acute Effects of Aerobic Exercise on Nocturnal and Pre-Sleep Arousal in Patients with Unipolar Depression: Preplanned Secondary Analysis of a Randomized Controlled Trial

Unipolar depression is associated with insomnia and autonomic arousal. The aim of this study was to quantify the effect of a single bout of aerobic exercise on nocturnal heart rate variability and pre-sleep arousal in patients with depression. This study was designed as a two-arm, parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients with a primary diagnosis of unipolar depression aged 18–65 years were included. The intervention consisted of a single 30 min moderate-intensity aerobic exercise bout. The control group sat and read for 30 min. The primary outcome of interest was RMSSD during the sleep period assessed with polysomnography. Secondary outcomes were additional heart rate variability outcomes during the sleep and pre-sleep period as well as subjective pre-sleep arousal. A total of 92 patients were randomized to either the exercise (N = 46) or the control (N = 46) group. Intent-to-treat analysis ANCOVA of follow-up sleep period RMSSD, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = 0.12, p = 0.94). There was no evidence for significant differences between both groups in any other heart rate variability measure nor in measures of cognitive or somatic pre-sleep arousal. As this is the first trial of its kind in this population, the findings need to be confirmed in further studies. Patients with depression should be encouraged to exercise regularly in order to profit from the known benefits on sleep and depressive symptoms, which are supported by extensive literature.

Abstract P208: Raas And Markers Of Renal Function In Response To Sleep Hygiene Interventions

Introduction: Recent epidemiologic studies report that shorter sleep duration is associated with a rapid decline in renal function. This project investigated the effects of 8 weeks of sleep hygiene interventions on the renin-angiotensin-aldosterone system (RAAS) regulation and markers of renal function. Accumulating evidence suggests that sleep plays an important role in blood pressure (BP) regulation. While BP is influenced by renal function, it is not known if improving sleep hygiene may support regulation of the RAAS. Methods: Fifty participants (59.8 ± 1.5 years; 31 women) completed 3 overnight in-hospital stays: baseline (S1), pre-intervention (S2) following a 4-week wait-list evaluation phase from S1 and post-intervention (S3). During S2, participants with elevated BP (BP>120/80 to <160/100) were randomly assigned to two sleep hygiene conditions where in both conditions, the sleep period was stabilized, but in one it was also lengthened. As the study is still ongoing, we remain blind to which condition participants were randomized to. Morning and evening plasma renin activity (PRA), urinary albumin, creatinine, and serum cystatin C levels were measured from all three stays. Albumin-to-creatinine ratio (ACR) and estimated glomerulus filtration rate (eGFR) were calculated. Results: There was a significant decrease of night PRA at post-intervention (S3) compared to S2 (p<0.05) and S1 (p<0.05). However, morning PRA did not show any changes throughout the stays (p=0.3). The urinary ACR obtained from evening urine samples did not show significant changes (p=0.66). In addition, serum cystatin C levels measured from evening blood draws and the eGFR did not show significant changes (p=0.21 and p=0.18, respectively). Conclusion: The sleep hygiene approach to improving sleep was associated with blunted PRA levels in the evening. When unblinded we will report on whether increasing the sleep period was more effective than stabilizing circadian placement of sleep, alone.