An automatic EEG-based sleep staging system with introducing NAoSP and NAoGP as new metrics for sleep staging systems

Different biological signals are recorded in sleep labs during sleep for the diagnosis and treatment of human sleep problems. Classification of sleep stages with electroencephalography (EEG) is preferred to other biological signals due to its advantages such as providing clinical information, cost-effectiveness, comfort, and ease of use. The evaluation of EEG signals taken during sleep by clinicians is a tiring, time-consuming, and error-prone method. Therefore, it is clinically mandatory to determine sleep stages by using software-supported systems. Like all classification problems, the accuracy rate is used to compare the performance of studies in this domain, but this metric can be accurate when the number of observations is equal in classes. However, since there is not an equal number of observations in sleep stages, this metric is insufficient in the evaluation of such systems. For this purpose, in recent years, Cohen’s kappa coefficient and even the sensitivity of NREM1 have been used for comparing the performance of these systems. Still, none of them examine the system from all dimensions. Therefore, in this study, two new metrics based on the polygon area metric, called the normalized area of sensitivity polygon and normalized area of the general polygon, are proposed for the performance evaluation of sleep staging systems. In addition, a new sleep staging system is introduced using the applications offered by the MATLAB program. The existing systems discussed in the literature were examined with the proposed metrics, and the best systems were compared with the proposed sleep staging system. According to the results, the proposed system excels in comparison with the most advanced machine learning methods. The single-channel method introduced based on the proposed metrics can be used for robust and reliable sleep stage classification from all dimensions required for real-time applications.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09641-2) contains supplementary material, which is available to authorized users.     

A transition-constrained discrete hidden Markov model for automatic sleep staging

Background

Principal component analysis (PCA) has been widely employed for automatic neuronal spike sorting. Calculating principal components (PCs) is computationally expensive, and requires complex numerical operations and large memory resources. Substantial hardware resources are therefore needed for hardware implementations of PCA. General Hebbian algorithm (GHA) has been proposed for calculating PCs of neuronal spikes in our previous work, which eliminates the needs of computationally expensive covariance analysis and eigenvalue decomposition in conventional PCA algorithms. However, large memory resources are still inherently required for storing a large volume of aligned spikes for training PCs. The large size memory will consume large hardware resources and contribute significant power dissipation, which make GHA difficult to be implemented in portable or implantable multi-channel recording micro-systems.

Method

In this paper, we present a new algorithm for PCA-based spike sorting based on GHA, namely stream-based Hebbian eigenfilter, which eliminates the inherent memory requirements of GHA while keeping the accuracy of spike sorting by utilizing the pseudo-stationarity of neuronal spikes. Because of the reduction of large hardware storage requirements, the proposed algorithm can lead to ultra-low hardware resources and power consumption of hardware implementations, which is critical for the future multi-channel micro-systems. Both clinical and synthetic neural recording data sets were employed for evaluating the accuracy of the stream-based Hebbian eigenfilter. The performance of spike sorting using stream-based eigenfilter and the computational complexity of the eigenfilter were rigorously evaluated and compared with conventional PCA algorithms. Field programmable logic arrays (FPGAs) were employed to implement the proposed algorithm, evaluate the hardware implementations and demonstrate the reduction in both power consumption and hardware memories achieved by the streaming computing

Results and discussion

Results demonstrate that the stream-based eigenfilter can achieve the same accuracy and is 10 times more computationally efficient when compared with conventional PCA algorithms. Hardware evaluations show that 90.3% logic resources, 95.1% power consumption and 86.8% computing latency can be reduced by the stream-based eigenfilter when compared with PCA hardware. By utilizing the streaming method, 92% memory resources and 67% power consumption can be saved when compared with the direct implementation of GHA.

Conclusion

Stream-based Hebbian eigenfilter presents a novel approach to enable real-time spike sorting with reduced computational complexity and hardware costs. This new design can be further utilized for multi-channel neuro-physiological experiments or chronic implants.     

A transition-constrained discrete hidden Markov model for automatic sleep staging

ABSTRACT: BACKGROUND: Approximately one-third of the human lifespan is spent sleeping. To diagnose sleep problems, all-night polysomnographic (PSG) recordings including electroencephalograms (EEGs), electrooculograms (EOGs) and electromyograms (EMGs), are usually acquired from the patient and scored by a well-trained expert according to Rechtschaffen & Kales (R&K) rules. Visual sleep scoring is a time-consuming and subjective process. Therefore, the development of an automatic sleep scoring method is desirable. METHOD: The EEG, EOG and EMG signals from twenty subjects were measured. In addition to selecting sleep characteristics based on the 1968 R&K rules, features utilized in other research were collected. Thirteen features were utilized including temporal and spectrum analyses of the EEG, EOG and EMG signals, and a total of 158 hours of sleep data were recorded. Ten subjects were used to train the Discrete Hidden Markov Model (DHMM), and the remaining ten were tested by the trained DHMM for recognition. Furthermore, the 2-fold cross validation was performed during this experiment. RESULTS: Overall agreement between the expert and the results presented is 85.29%. With the exception of S1, the sensitivities of each stage were more than 81%. The most accurate stage was SWS (94.9%), and the least-accurately classified stage was S1 (<34%). In the majority of cases, S1 was classified as Wake (21%), S2 (33%) or REM sleep (12%), consistent with previous studies. However, the total time of S1 in the 20 all-night sleep recordings was less than 4%. CONCLUSION: The results of the experiments demonstrate that the proposed method significantly enhances the recognition rate when compared with prior studies.     

Correction to: Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography

Sleep and Biological Rhythms -     

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...     

Genetics of sleep and sleep disorders

Sleep remains one of the least understood phenomena in biology--even its role in synaptic plasticity remains debatable. Since sleep was recognized to be regulated genetically, intense research has launched on two fronts: the development of model organisms for deciphering the molecular mechanisms of sleep and attempts to identify genetic underpinnings of human sleep disorders. In this Review, we describe how unbiased, high-throughput screens in model organisms are uncovering sleep regulatory mechanisms and how pathways, such as the circadian clock network and specific neurotransmitter signals, have conserved effects on sleep from Drosophila to humans. At the same time, genome-wide association studies (GWAS) have uncovered ～14 loci increasing susceptibility to sleep disorders, such as narcolepsy and restless leg syndrome. To conclude, we discuss how these different strategies will be critical to unambiguously defining the function of sleep.     

Overview of sleep and sleep medicine in Asian countries

While there are a number of sleep medicine and sleep research publications in Asia, and their quality is increasing each year, the actual situation of sleep disorders in the general population still remains an issue of major concern. Scientists and medical doctors believe that, for the first time in history, the general lack of sleep could lead to a diminution of life expectancy. It is also known that, as people are working more and more and are more tired, they are more likely to become victims of accidents. Most of the time these incidents have little gravity, but sometimes they can cost thousands of innocent lives or contribute to disasters such as the Chernobyl nuclear plant explosion or the Bhopal gas tragedy. Based on the Asian Sleep Research Society Summit and Symposium Round Table held during the fall of 2009 on Okinawa, this review aims to give an accurate view of the actual situation of sleep research and medicine in Asia. The particular example of the obstructive sleep apnea syndrome will illustrate the importance of sleep medicine in this part of the world. Finally, the actual situation will be discussed to elaborate some possible strategies to improve the sleep situation for Asian populations.

     

A staging system for mouse limb development

A series of 15 stages of development for the mouse limb bud have been defined, spanning the time from the first appearance of the limb bud to the completion of limb outgrowth. The stages are based on changes in the morphology of the limb in living preparations. The development and regression of the apical ectodermal ridge (AER) as well as the development of the skeletal structures are also described. This staging system has been developed in response to the need to standardize in situ experimental analyses of the mouse limb bud. Comparable stages of the commonly used chick wing and mouse whole embryo systems are presented.     

固态间歇补料乙醇生料发酵新工艺

浓醪发酵是酒精生产的发展方向。与现行酒精厂普遍采用的热蒸煮工艺相比, 生料发酵技术的发展使得浓醪发酵更容易进行。本研究首次在生料发酵中直接采用固态原料间歇补料, 比较了STARGENTM生淀粉水解酶间歇补料工艺和传统无补料工艺, 并对不同补料方式进行了研究。结果表明: 与传统无补料生料发酵工艺相比, 在相同的干基配料浓度30%、相同的生料酶添加量0.22%(W/W)的条件下, 采用15%的起始配料浓度、发酵15~25 h进行间歇补料的新工艺, 酒精产量从17.06%提高到18.50%。该间歇补料优化工艺的建立, 丰富了生料发酵技术的应用。     

Masseter EMG activity during sleep and sleep bruxism

The masseter muscle is involved in the complex and coordinated oromotor behaviors such as mastication during wakefulness. The masseter electromyographic (EMG) activity decreases but does not disappear completely during sleep: the EMG activity is generally of low level and inhomogeneous for the duration, amplitude and intervals. The decreased excitability of the masseter motoneurons can be determined by neural substrates for NREM and REM sleep. The masseter EMG activity is increased in association with the level of arousal fluctuations within either sleep state. In addition, there are some motor events such as REM twitches, swallowing and rhythmic masticatory muscle activity (RMMA), whose generation might involve the additional activation of specific neural circuits. Sleep bruxism (SB) is characterized by exaggerated occurrence of RMMA. In SB, the rhythmic activation of the masseter muscle can reflect the rhythmic motor inputs to motoneurons through, at least in part, common neural circuits for generating masticatory rhythm under the facilitatory influences of transient arousals. However, it remains elusive as to which neural circuits determine the genesis of sleep bruxism. Based on the available knowledge on the masseter EMG activity during sleep, this review presents that the variety of the masseter EMG phenotypes during sleep can result from the combinations of the quantitative, spatial and temporal neural factors eventually sending net facilitatory inputs to trigeminal motoneurons under sleep regulatory systems.     

Effect of sleep and circadian cycle on sleep period energy expenditure

Energy expenditure is lower during sleep than relaxed wakefulness. However, there is disagreement as to the particular metabolic changes that produce the difference. The present study assessed the contribution of sleep, circadian cycle, and the specific dynamic action effect of the evening meal to the sleep period fall in metabolic rate. Five subjects were tested for a total of nine nights under three conditions in a repeated-measures design. Subjects were confined to bed throughout their usual sleep period but were instructed to go to sleep 0, 3, or 6 h after their usual time for lights out. O2 consumption was measured in all conditions for the 0.5 h before and after each of the times for lights out and then throughout the sleep period after lights out. The results demonstrated that changes in energy expenditure during the sleep period are a function of both sleep and circadian cycle. In this study, the contribution of the two components was approximately equal. However, the effect of sleep was rapid asymptoting within 15 min of sleep onset, whereas that of circadian cycle was constant over the assessment period.     

Immunohistological markers for staging neurogenesis in adult hippocampus

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus occurs constitutively throughout postnatal life, and the rate of neurogenesis within the DG can be altered under various physiological and pathophysiological conditions. Adult neurogenesis includes the process in which the division of a precursor cell takes place and the multi-step process (proliferation, differentiation, migration, targeting, and synaptic integration) that ends with the formation of a postmitotic functionally integrated new neuron. During specific time-frames of adult neurogenesis, various markers are expressed that correlate with the differentiation steps along the pathway from early progenitor cells to newly generated postmitotic neurons within the DG. Markers that are currently widely used for the investigation of adult hippocampal neurogenesis are: glial fibrillary acidic protein, nestin, Pax6, NeuroD, PSA-NCAM, doublecortin, TUC-4, Tuj-1, and calretinin. The discovery and development of specific markers that allow the time-course and fate of neurons to be followed during adult neurogenesis in a detailed and precise fashion are not only helpful for gaining further insights into the genesis of new neurons in the hippocampus, but also might be applicable to the development of strategies for therapeutic interventions. This study was supported by the DFG (SFB 636/A5).     

Antioxidant defense responses to sleep loss and sleep recovery

Sleep deprivation in humans is widely believed to impair health, and sleep is thought to have powerful restorative properties. The specific physical and biochemical factors and processes mediating these outcomes, however, are poorly elucidated. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality. Metabolic and immunological consequences of sleep deprivation point to a high potential for antioxidant imbalance. The objective, therefore, was to study glutathione content in the liver, heart, and lung, because glutathione is considered a major free radical scavenger that reflects the degree to which a tissue has been oxidatively challenged. We also investigated major enzymatic antioxidants, including catalase and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase activity and glutathione content, which normally are tightly regulated, were both decreased in liver by 23-36% by 5 and 10 days of sleep deprivation. Such levels are associated with impaired health in other animal models of oxidative stress-associated disease. The decreases were accompanied by markers of generalized cell injury and absence of responses by the other enzymatic antioxidants under study. Enzymatic activities in the heart indicated an increased rate of oxidative pentose phosphate pathway activity during sleep deprivation. Recovery sleep normalized antioxidant content in liver and enhanced enzymatic antioxidant activities in both the liver and the heart. The present results link uncompensated oxidative stress to health effects induced by sleep deprivation and provide evidence that restoration of antioxidant balance is a property of recovery sleep.     

Genetics of sleep

Main achievements in general and molecular genetics of sleep, especially NREM sleep, are regarded. Among them, discovery of such heredity disorders, as FFI, FASPS and DSPS, the finding of genetic hallmarks of sleep EEG, etc.     

Effect of sleep and sleep deprivation on ventilatory response to bronchoconstriction

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.     

Characteristics of sleep structure in patients with sleep apnea]

The course of different sleep phases has been studied in group of patients. A decrease in duration of deep sleep phase and increase in the number of awakenings are found in them.     

Sleep staging with movement-related signals

Body movement related signals (i.e., activity due to postural changes and the ballistocardiac effort) were recorded from six normal volunteers using the static-charge-sensitive bed (SCSB). Visual sleep staging was performed on the basis of simultaneously recorded EEG, EMG and EOG signals. A statistical classification technique was used to determine if reliable sleep staging could be performed using only the SCSB signal. A classification rate of between 52% and 75% was obtained for sleep staging in the five conventional sleep stages and the awake state. These rates improved from 78% to 89% for classification between awake, REM and non-REM sleep and from 86% to 98% for awake versus asleep classification.     

The staging and treatment of epithelial ovarian cancer.

Recent advances in the staging of ovarian cancer have suggested that many patients with apparently localized (stage I or II) disease have occult dissemination within the abdomen. Approximately 20% of patients classified at laparotomy as having stage I or II ovarian cancer are found by lymphangiography to have abnormal retroperitoneal lymph nodes. In many other patients advanced disease is also detected by peritonescopy; with this technique metastases are often discovered on the undersurface of the right diaphragm. These findings may help explain the high rates of recurrence after surgical resection or pelvic irradiation, or both, in patients with localized disease. Studies are in progress to determine whether modification of the radiotherapy field to include the right diaphragm will improve survival. Along with improved staging, histologic grading of the degree of anaplasia of the tumour tissue may permit more precise determination of prognosis and therefore better design of therapy. Adjuvant radiotherapy has not yet been shown to improve the survival of patients with stage I disease, but the 5-year survival of patients with stage II disease is greater for those receiving postoperative radiotherapy than for those undergoing surgery alone. For most patients with advanced disease radiotherapy is palliative only and carries a high risk of long-term complications. Numerous chemotherapeutic agents used singly can produce an objective response by tumour. Preliminary data suggest that combination chemotherapy can increase the rate of objective response, but a longer follow-up period is necessary to determine whether this form of therapy can improve survival.     

Biomarkers and clinical staging in psychiatry

Personalized medicine is rapidly becoming a reality in today's physical medicine. However, as yet this is largely an aspirational goal in psychiatry, despite significant advances in our understanding of the biochemical, genetic and neurobiological processes underlying major mental disorders. Preventive medicine relies on the availability of predictive tools; in psychiatry we still largely lack these. Furthermore, our current diagnostic systems, with their focus on well‐established, largely chronic illness, do not support a pre‐emptive, let alone a preventive, approach, since it is during the early stages of a disorder that interventions have the potential to offer the greatest benefit. Here, we present a clinical staging model for severe mental disorders and discuss examples of biological markers that have already undergone some systematic evaluation and that could be integrated into such a framework. The advantage of this model is that it explicitly considers the evolution of psychopathology during the development of a mental illness and emphasizes that progression of illness is by no means inevitable, but can be altered by providing appropriate interventions that target individual modifiable risk and protective factors. The specific goals of therapeutic intervention are therefore broadened to include the prevention of illness onset or progression, and to minimize the risk of harm associated with more complex treatment regimens. The staging model also facilitates the integration of new data on the biological, social and environmental factors that influence mental illness into our clinical and diagnostic infrastructure, which will provide a major step forward in the development of a truly pre‐emptive psychiatry.     

Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice

Ghrelin is well known for its feeding and growth hormone-releasing actions. It may also be involved in sleep regulation; intracerebroventricular administration and hypothalamic microinjections of ghrelin stimulate wakefulness in rats. Hypothalamic ghrelin, together with neuropeptide Y and orexin form a food intake-regulatory circuit. We hypothesized that this circuit also promotes arousal. To further investigate the role of ghrelin in the regulation of sleep-wakefulness, we characterized spontaneous and homeostatic sleep regulation in ghrelin knockout (KO) and wild-type (WT) mice. Both groups of mice exhibited similar diurnal rhythms with more sleep and less wakefulness during the light period. In ghrelin KO mice, spontaneous wakefulness and rapid-eye-movement sleep (REMS) were slightly elevated, and non-rapid-eye-movement sleep (NREMS) was reduced. KO mice had more fragmented NREMS than WT mice, as indicated by the shorter and greater number of NREMS episodes. Six hours of sleep deprivation induced rebound increases in NREMS and REMS and biphasic changes in electroencephalographic slow-wave activity (EEG SWA) in both genotypes. Ghrelin KO mice recovered from NREMS and REMS loss faster, and the delayed reduction in EEG SWA, occurring after sleep loss-enhanced increases in EEG SWA, was shorter-lasting compared with WT mice. These findings suggest that the basic sleep-wake regulatory mechanisms in ghrelin KO mice are not impaired and they are able to mount adequate rebound sleep in response to a homeostatic challenge. It is possible that redundancy in the arousal systems of the brain or activation of compensatory mechanisms during development allow for normal sleep-wake regulation in ghrelin KO mice.