pyActigraphy: Open-source python package for actigraphy data visualization and analysis

Over the past 40 years, actigraphy has been used to study rest-activity patterns in circadian rhythm and sleep research. Furthermore, considering its simplicity of use, there is a growing interest in the analysis of large population-based samples, using actigraphy. Here, we introduce pyActigraphy, a comprehensive toolbox for data visualization and analysis including multiple sleep detection algorithms and rest-activity rhythm variables. This open-source python package implements methods to read multiple data formats, quantify various properties of rest-activity rhythms, visualize sleep agendas, automatically detect rest periods and perform more advanced signal processing analyses. The development of this package aims to pave the way towards the establishment of a comprehensive open-source software suite, supported by a community of both developers and researchers, that would provide all the necessary tools for in-depth and large scale actigraphy data analyses.     

Reduction in Ultrasonic Vocalizations in Pups Born to Rapid Eye Movement Sleep Restricted Mothers in Rat Model

The effects of rapid eye movement sleep restriction (REMSR) in rats during late pregnancy were studied on the ultrasonic vocalizations (USVs) made by the pups. USVs are distress calls inaudible to human ears. Rapid eye movement (REM) sleep was restricted in one group of pregnant rats for 22 hours, starting from gestational day 14 to 20, using standard single platform method. The USVs of male pups were recorded after a brief isolation from their mother for two minutes on alternate post-natal days, from day one till weaning. The USVs were recorded using microphones and were analysed qualitatively and quantitatively using SASPro software. Control pups produced maximum vocalization on post-natal days 9 to 11. In comparison, the pups born to REMSR mothers showed not only a reduction in vocalization but also a delay in peak call making days. The experimental group showed variations in the types and characteristics of call types, and alteration in temporal profile. The blunting of distress call making response in these pups indicates that maternal sleep plays a role in regulating the neural development involved in vocalizations and possibly in shaping the emotional behaviour in neonates. It is suggested that the reduced ultrasonic vocalizations can be utilized as a reliable early marker for affective state in rat pups. Such impaired vocalization responses could provide an important lead in understanding mother-child bonding for an optimal cognitive development during post-partum life. This is the first report showing a potential link between maternal REM sleep deprivation and the vocalization in neonates and infants.     

Measurement of pharyngeal cross-sectional area by finite element analysis.

A noninvasive measurement of pharyngeal cross-sectional area (CSA) during sleep would be advantageous for research studies. We hypothesized that CSA could be calculated from the measured pharyngeal pressure and flow by finite element analysis (FEA). The retropalatal airway was visualized by using a fiber-optic scope to obtain the measured CSA (mCSA). Flow was measured with a pneumotachometer, and pharyngeal pressure was measured with a pressure catheter at the palatal rim. FEA was performed as follows: by using a three-dimensional image of the upper airway, a mesh of finite elements was created. Specialized software was used to allow the simultaneous calculation of velocity and area for each element by using the measured pressure and flow. In the development phase, 677 simultaneous measurements of CSA, pressure, and flow from one subject during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were entered into the software to determine a series of equations, based on the continuity and momentum equations, that could calculate the CSA (cCSA). In the validation phase, the final equations were used to calculate the CSA from 1,767 simultaneous measurements of pressure and flow obtained during wakefulness, NREM, and REM sleep from 14 subjects. In both phases, mCSA and cCSA were compared by Bland-Altman analysis. For development breaths, the mean difference between mCSA and cCSA was 0.0 mm2 (95% CI, -0.1, 0.1 mm2). For NREM validation breaths, the mean difference between mCSA and cCSA was 1.1 mm2 (95% CI 1.3, 1.5 mm2). Pharyngeal CSA can be accurately calculated from measured pharyngeal pressure and flow by FEA.     

Sleep in brain development

With the discovery of rapid eye movement (REM) sleep, sleep was no longer considered a homogeneous state of passive rest for the brain. On the contrary, sleep, and especially REM sleep, appeared as an active condition of intense cerebral activity. The fact that we get large amounts of sleep in early life suggested that sleep may play a role in brain maturation. This idea has been investigated for many years through a large number of animal and human studies, but evidence remains fragmented. The hypothesis proposed was that REM sleep would provide an endogenous source of activation, possibly critical for structural maturation of the central nervous system. This proposal led to a series of experiments looking at the role of REM sleep in brain development. In particular, the influence of sleep in developing the visual system has been highlighted. More recently, non-REM (NREM) sleep state has become a major focus of attention. The current data underscore the importance of both REM sleep and NREM sleep states in normal synaptic development and lend support to their functional roles in brain maturation. Both sleep states appear to be important for neuronal development, but the corresponding contribution is likely to be different.     

基于蓝牙4.0的便携式睡眠监测仪的研制

目的:实时监测睡眠状况,从而帮助人们特别是老人找到影响睡眠的原因。方法:设计了一个低功耗便携式睡眠监测仪,它是通过加速度传感器采集腕动信号、蓝牙4.0低功耗无线传输、Micro-SD卡存储、上位机显示等实现对睡眠状态的检测。为了验证睡眠监测仪的准确性,本文采用了视频分析方法,并且对不同人群进行监测。结果:研制的睡眠监测仪具有便携低功耗等特点,能够准确监测睡眠状态。结论:睡眠监测仪的研制对使用者特别是老人帮助很大,能够帮助使用者方便适时了解自己的睡眠状况,找到影响睡眠原因和改善睡眠质量方法。     

A novel machine learning unsupervised algorithm for sleep/wake identification using actigraphy

ABSTRACT

Actigraphy is widely used in sleep studies but lacks a universal unsupervised algorithm for sleep/wake identification. An unsupervised algorithm is useful in large-scale population studies and in cases where polysomnography (PSG) is unavailable, as it does not require sleep outcome labels to train the model but utilizes information solely contained in actigraphy to learn sleep and wake characteristics and separate the two states. In this study, we proposed a machine learning unsupervised algorithm based on the Hidden Markov Model (HMM) for sleep/wake identification. The proposed algorithm is also an individualized approach that takes into account individual variabilities and analyzes each individual actigraphy profile separately to infer sleep and wake states. We used Actiwatch and PSG data from 43 individuals in the Multi-Ethnic Study of Atherosclerosis study to evaluate the method performance. Epoch-by-epoch comparisons and sleep variable comparisons were made between our algorithm, the unsupervised algorithm embedded in the Actiwatch software (AS), and the pre-trained supervised UCSD algorithm. Using PSG as the reference, the accuracy was 85.7% for HMM, 84.7% for AS, and 85.0% for UCSD. The sensitivity was 99.3%, 99.7%, and 98.9% for HMM, AS, and UCSD, respectively, and the specificity was 36.4%, 30.0%, and 31.7%, respectively. The Kappa statistic was 0.446 for HMM, 0.399 for AS, and 0.311 for UCSD, suggesting fair to moderate agreement between PSG and actigraphy. The Bland–Altman plots further show that the total sleep time, sleep latency, and sleep efficiency estimates by HMM were closer to PSG with narrower 95% limits of agreement than AS and UCSD. All three methods tend to overestimate sleep and underestimate wake compared to PSG. Our HMM approach is also able to differentiate relatively active and sedentary individuals by quantifying variabilities in activity counts: individuals with higher estimated activity variabilities tend to show more frequent sedentary behaviors. Our unsupervised data-driven HMM algorithm achieved better performance than the commonly used Actiwatch software algorithm and the pre-trained UCSD algorithm. HMM can help expand the application of actigraphy in cases where PSG is hard to acquire and supervised methods cannot be trained. In addition, the estimated HMM parameters can characterize individual activity patterns and sedentary tendencies that can be further utilized in downstream analysis.     

Availability of a simple self-report sleep questionnaire for 9- to 12-year-old children

Self-report questionnaires about sleep habits are useful for population-based studies because of their low cost. However, there is no valid and reliable self-report sleep questionnaire for elementary school-aged children. The aim of this study was to examine the availability of a simple self-report sleep questionnaire for 9- to 12-year-old children. Participants were 58 children aged 9–12 years from one elementary school in a rural area of Japan. Participants wore an accelerometer for 10 consecutive days and completed the sleep questionnaire twice. Sleep measures included bedtime, wake time, and assumed and actual sleep duration on weekdays and weekends. The data obtained from the accelerometer and sleep/wake scoring software were used to assess criterion validity. Pearson correlation coefficients and Bland-Altman plots were used to evaluate the relationships between objective and self-reported sleep measures. Test-retest reliability was evaluated using intraclass correlation coefficients. The correlations between the objective and questionnaire measures were moderate to high (r = 0.45 to 0.90) and significant, except girls’ wake time, assumed sleep duration, and actual sleep duration on weekends. The Bland-Altman plots indicated that bedtime and wake time obtained from the questionnaire were underestimated for both weekdays and weekends. Test-retest reliability of the questionnaire was high, with intraclass coefficients ranging from 0.71 to 0.99. Although caution should be exercised when evaluating sleep duration on weekends, this simple self-reported sleep questionnaire is a useful tool for assessing sleep habits in 9- to 12-year-old children, particularly in school-based and large-scale epidemiological studies.

     

Evaluation of a commercially available automated sleep staging tool in healthy infants

Sleep and Biological Rhythms - The ALICE5 software package provides a commercially available automated sleep staging system designed for infants. This study aims to evaluate the accuracy of this...     

Video tracking and analysis of sleep in Drosophila melanogaster

In the past decade, Drosophila has emerged as an ideal model organism for studying the genetic components of sleep as well as its regulation and functions. In fruit flies, sleep can be conveniently estimated by measuring the locomotor activity of the flies using techniques and instruments adapted from the field of circadian behavior. However, proper analysis of sleep requires degrees of spatial and temporal resolution higher than is needed by circadian scientists, as well as different algorithms and software for data analysis. Here I describe how to perform sleep experiments in flies using techniques and software (pySolo and pySolo-Video) previously developed in my laboratory. I focus on computer-assisted video tracking to monitor fly activity. I explain how to plan a sleep analysis experiment that covers the basic aspects of sleep, how to prepare the necessary equipment and how to analyze the data. By using this protocol, a typical sleep analysis experiment can be completed in 5-7 d.     

Developmental changes in the complexity of the electrocortical activity in foetal sheep.

The foetal sheep brain develops organised sleep states from 115-120 d gestational age (dGA, term 150 dGA) alternating between REM and NREM sleep. We aimed to investigate whether maturation of REM or NREM sleep generating structures leads to the development of distinct sleep states. The electrocorticogram (ECoG) was recorded from five unanaesthetised chronically instrumented foetal sheep in utero and was analysed every 5th day between 115-130 dGA by two different non-linear methods. We calculated a non-linear prediction error which quantifies the causality of the ECoG and applied bispectral analysis which quantifies non-linear interrelations of single frequency components within the ECoG signal. The prediction error during REM sleep was significantly higher than during NREM sleep at each investigated age (P<0.0001) coincidental with poor organisation of the rhythmic pattern in the ECoG during REM sleep. At 115 dGA, organised sleep states defined behaviourally were not developed yet. The prediction error, however, showed already different states of electrocortical activity that were not detectable using power spectral analysis. The prediction error of the premature NREM sleep ECoG decreased significantly during emergence of organised sleep states between 115 and 120 dGA and continued to decrease after the emergence of distinct sleep states (P<0.05). The prediction error of the premature REM sleep ECoG did not change until 120 dGA and began to increase at 125 dGA (P<0.05). Using bispectral analysis, we showed couplings between delta waves (1.5-4 Hz) and frequencies in the range of spindle waves (4-8 and 8-12 Hz) during NREM sleep that became closer during development. The results show that maturation of ECoG synchronisation mediating structures is important for the development of organised sleep states. The further divergence of the prediction error of NREM and REM sleep after development of organised sleep states reveals continuous functional development. Thus, complementary application of non-linear ECoG analysis to power spectral analysis provide new insights in the collective behaviour of the neuronal network during the emergence of sleep states.     

Actigraphic sleep and developmental progress of one-year-old infants

The aims of this study were to pilot methods to monitor the sleep of infants, as well as explore the relationships between infant sleep and physical, cognitive and motor development. Fifty-two one-year-old infants and their parents participated in the study. Infant sleep was assessed by one week’s actigraphy, sleep diaries and by the Brief Infant Sleep Questionnaire. Parents also completed a background questionnaire and the Ages and Stages Questionnaire to measure stages of development across five domains. Infant’s weight and length were measured by the researcher at study onset and Body Mass Index (BMI) scores were calculated. Sleep efficiency, and having a higher proportion of total sleep at night, were significantly correlated with age as well as stages of cognitive and motor development. However, sleep measures were not correlated with infant BMI. These findings support increasing evidence that sleep matures quickly around the age of one year and is related to other stages of development. Further research is required to confirm whether links between sleep and development are simply a marker of maturation, or if sleep per se plays a specific role in infant cognitive and motor development. Sleep and physical growth at this age need further investigation with a more representative sample including short-sleeping and overweight infants.

     

Sleep enhances plasticity in the developing visual cortex

During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.     

Analysis of the action of a neuropeptide that induces delta-sleep in cats and white rats

Suboccipital administration of the oligopeptide in a dose 15 or 20 micrograms/kg evokes within 15--20 min the electrographic (delta-sleep) and behavioural sleep in cats and albino rats. Oligopeptide administration significantly increases threshold reactions of EEG to sonic stimulation. Significant delay (for 50--90 min) of the development of paradoxical sleep was observed which is considered as a manifestation of inhibition of further development of sleep mechanisms due to the effect of neuropeptide. The data obtained indicate that natural sleep is not identical to that induced by the neuropeptide.     

Extended nights, sleep loss, and recovery sleep in adolescents

In summary, this study of sleep in adolescents on an atypical schedule of 18-hour nights showed marked but not unanticipated differences in sleep as function of prior sleep deprivation. Unanticipated was the evidence of "recovery" sleep in adolescents who not only were not sleep deprived, but who had been on a sleep "optimizing" schedule and had been awake for only 10 hours. Extended sleep beginning about 4 hours in advance of entrained sleep onset phase was not associated with a return of SWS, a finding coinciding with predictions from studies in adults. Finally, this study provides an indication that the homeostatic sleep/wake process becomes less robust or sleep responsive during adolescent development, a phenomenon that may influence the delay of sleep common in adolescents.     

Iron-Deficiency Anemia is Associated with Altered Characteristics of Sleep Spindles in NREM Sleep in Infancy

Objective To determine the effects of iron-deficiency anemia on the development of non-rapid-eye-movement (NREM) sleep stages, as indexed by sleep spindles. Study design Patterns of sleep spindles during NREM sleep stages 2 and 3–4 (slow-wave-sleep, SWS) were compared in 26 otherwise healthy 6-month-old Chilean infants with iron-deficiency anemia and 18 non-anemic control infants. From polygraphic recordings, EEG activity was analyzed for sleep spindles to assess their number (density), duration, frequency, and inter-spindle interval. Results Iron-deficient anemic infants differed from the control group by having sleep spindles with reduced density, lower frequency, and longer inter-spindle intervals in NREM sleep stage 2 and SWS. Conclusions These results provide evidence of delayed sleep spindle patterns in iron-deficient anemic infants, suggesting that iron is an essential micronutrient for the normal progression of NREM sleep pattern development in the human. Special issue dedicated to Dr. Moussa Youdim.     

Segmental organization of sleep

Segmental organization of sleep was studied in healthy subjects and insomniac patients. Theoretical and practical aspects of sleep organization are discussed. The disintegration syndrome (decreased stability of development of sleep stage segments and change in sleep stage sequence characteristic of normal sleep) is an inherent feature of sleep disorders and a fine index of adaptive possibilities of sleep systems. It is suggested that each segment of any sleep stage has its specific functional role different from the functional significance of the stage as a whole. Depending on the time of appearance of any specific segment, it can be an important preliminary of transition to another functional state and be involved in preparation for triggering corresponding sleep-organizing systems. At the same time, it can be a reflection of the process of estimation of the achieved result. The dynamic change in sleep stages is determined by subsequent activation of different brain structures and also suggests a possibility of a change in the functional role of a certain stage depending on the initial functional state of sleep systems.     

阻塞性睡眠呼吸暂停诱发肠道菌群紊乱与动脉粥样硬化关系的进展

阻塞性睡眠呼吸暂停是一种常见的呼吸疾病,其与动脉粥样硬化的发生发展密切相关。近年来,随着对肠道菌群的深入探索,越来越多的研究发现肠道菌群与阻塞性睡眠呼吸暂停和动脉粥样硬化均密切相关,并且可能在二者之间起桥梁作用,其主要表现在阻塞性睡眠呼吸暂停可诱发肠道菌群失调、肠道屏障受损和肠道代谢产物改变,而这些改变可能参与了阻塞性睡眠呼吸暂停促进动脉粥样硬化发生发展的过程。本文就这些研究作一综述,以期为探讨阻塞性睡眠呼吸暂停致动脉粥样硬化的发生机制和治疗提供新的思路。     

No elevated plasma catecholamine levels during sleep in newly diagnosed, untreated hypertensives

The sympatho-adrenergic system is highly involved in regulating sleep, wake and arousal states, and abnormalities in this system are regarded as a key factor in the development and progression of arterial hypertension. While hypertension is associated with a hyperadrenergic state during wakefulness, the effect of hypertension on plasma-catecholamine levels during sleep is not yet known. Twelve young participants with newly diagnosed, untreated hypertension and twelve healthy controls slept for 7 hours in the sleep laboratory. Before and after sleep, subjects rested in a supine position for 3-h periods of wakefulness. We sampled blood at a fast rate (1/10 min) and monitored blood pressure and heart rate continuously. We show that plasma NE and E levels did not differ between hypertensives and normotensive during sleep as well as before and after sleep. Blood pressure was higher in hypertensives, reaching the largest group difference in the morning after sleep. Unlike in the normotensives, in the hypertensive participants the morning rise in blood pressure did not correlate with the rise in catecholamine levels at awakening. Our results suggest that hypertension in its early stages is not associated with a strong hyperadrenergic state during sleep. In showing a diminished control of blood pressure through sympatho-adrenergic signals in hypertensive participants, our data point towards a possible involvement of dysfunctional sleep-related blood pressure regulation in the development of hypertension.     

Influence of Chronotype,Season, and Sex of Subject on Sleep Behavior of Young Adults

The aim of this study was to investigate whether sex, season, and/or chronotype influence the sleep behavior of university students. Detailed data were collected on activity/rest patterns by wrist actigraphy combined with diaries. Thirty‐four medical students (19 female and 15 male) were monitored by Actiwatch® actometers for 15 consecutive days in May and again in November. The data of a modified Horne and Östberg chronotype questionnaire, which were collected from 1573 female and 1124 male medical school students surveyed in the spring and autumn over an eight‐year period, were evaluated. Actiwatch® sleep analysis software was used to process the activity data with statistical analyses performed with ANOVA. We found no significant sex‐specific differences in sleep efficiency, sleep onset latency, or actual sleep‐time duration. However, we did find a difference in sleep efficiency between morning and evening types, with morning types having a higher sleep efficiency (87.9%, SD=1.3) than evening types (84.3%, SD=0.87%; p=0.007). Seasonal differences were also detected: the actual sleep‐time duration in autumn was significantly longer (mean 6.9 h, SD=0.13 h) than in spring (6.6 h, SD=0.1 h; p=0.013). Evaluation of the chronotype questionnaire data showed that individuals with no special preference for morningness or eveningness (i.e., so‐called intermediates) were most common. The distribution of chronotypes was related to the sex of subject. Men displayed eveningness significantly more often than women (28.9% males vs. 20.8% females; p<0.001), while females exhibited greater morningness (20.3% females vs.15.6% males; p<0.001). Sex influences chronotype distribution, but not actual sleep time‐duration, sleep onset latency, or sleep efficiency. The latter, however, differed among chronotypes, while actual sleep‐time duration was affected by season.     

Covert waking brain activity reveals instantaneous sleep depth

The neural correlates of the wake-sleep continuum remain incompletely understood, limiting the development of adaptive drug delivery systems for promoting sleep maintenance. The most useful measure for resolving early positions along this continuum is the alpha oscillation, an 8-13 Hz electroencephalographic rhythm prominent over posterior scalp locations. The brain activation signature of wakefulness, alpha expression discloses immediate levels of alertness and dissipates in concert with fading awareness as sleep begins. This brain activity pattern, however, is largely ignored once sleep begins. Here we show that the intensity of spectral power in the alpha band actually continues to disclose instantaneous responsiveness to noise--a measure of sleep depth--throughout a night of sleep. By systematically challenging sleep with realistic and varied acoustic disruption, we found that sleepers exhibited markedly greater sensitivity to sounds during moments of elevated alpha expression. This result demonstrates that alpha power is not a binary marker of the transition between sleep and wakefulness, but carries rich information about immediate sleep stability. Further, it shows that an empirical and ecologically relevant form of sleep depth is revealed in real-time by EEG spectral content in the alpha band, a measure that affords prediction on the order of minutes. This signal, which transcends the boundaries of classical sleep stages, could potentially be used for real-time feedback to novel, adaptive drug delivery systems for inducing sleep.