SLEEP AND ITS PHASES
“A sleeping man holds in a circle around him the thread of the hours, the order of years and of worlds“, as Marcel Proust described – in his most important work  – the wonderful and fascinating sleep mechanisms.
The Academic American Encyclopedia defines sleep a “normal, reversible, recurrent state of reduced responsiveness to external stimulation that is accompanied by complex and predictable changes in physiology”. During sleep, spontaneous and coordinated activities of the central and peripheral nervous systems, fluctuations in the secretion of hormones and changes in muscle tone occur in a completely involuntary way.
Sleep activity is characterized by two main phases: REM (Rapid Eye Movement) and N-REM. Non-REM sleep is usually divided into four stages, during which sleep gets deeper and deeper; while in REM sleep no stages are identified, except for specific research purposes.
The phases and stages of sleep can be recorded and analyzed through a medical examination called polysomnography, which involves the placement of detectors on the skin in various points of the body such as the head, face, chest and legs (see Figure 1). These detectors transmit, to a recording and filing system, impulses related to the activity of the brain (brain waves), of some muscles (movements of eyes and upper and lower limbs) and of the cardiovascular (heart rate) and respiratory (breath rate) systems. The data collected by the polysomnography are expressed in the form of a trace which shows, in parallel, the graphs relating to all the activities listed above, giving physicians the possibility to define the precise structure and trends of sleep.
An ideal sequence of sleep phases and stages shows – in polysomnography – the transition from the waking state to the N-REM sleep phase starting from the first stage, to continue with the following ones. At stage 4 of N-REM phase, REM sleep follows.
A normal sleep chart – hypnogram – shows the non-REM and REM phases following each other for 4-5 cycles of approximately 90 minutes (see Figure 2). In correspondence with the passages from the N-REM to the REM phase, and vice versa, very brief awakenings occur during which the person is unconscious and, therefore, does not keep the memory of them.
The regulation of sleep-wakefulness cycle is articulated thanks to two distinct biological systems which, working in parallel, help to determine when to fall asleep and when to wake up. Such mechanisms are known as the circadian rhythm, or C process, and sleep homeostasis, or S process (see Figure 3).
Process C is a regulation cycle that changes the individual’s alert levels (wake drive) during the day by interacting closely with stimulations coming from the environment. It is influenced by the functioning of our biological clock, a system located in an area of the brain called the suprachiasmatic nucleus of the hypothalamus. The release of melatonin, a hormone produced by the epiphysis according to the intensity of light (the darker it is, the more it is produced) contributes to the proper functioning of the circadian rhythm, which also help to regulate stress working as a cortisol antagonist.
Research conducted on the biological clock  found that this system is influenced by genes which can determine sleep settings changing from one person to another. In particular, it has been shown that the “Period” gene is capable of producing a protein that accumulates in the cell during the night and is then degraded during the day. It is known, in fact, that there are individuals who wake up early without difficulty, falling asleep just as early in the evening, and others who tend to stay up late, still having a normal sleep and getting up later in the morning. The former, in the language of sleep experts, are defined as larks and the latter owls, to associate them with species of birds that are, respectively, early risers and nocturnal. Having a “lark” or “owl” sleep/wake rhythm depends on the genetic programming of the biological clock, but it can also undergo changes over time based on our lifestyle habits.
The S process, on the other hand, reflects the action of homeostatic factors that increase the need for sleep (sleep drive) exponentially with the passing of waking time. This mechanism ensures that, when awake, the body proceeds to accumulate hypnogenic molecules which progressively increase the individual’s tendency to fall asleep, until a level is reached where it becomes practically impossible to keep awake. When the body rests during the night, these molecules are disposed of and their production begins again only when the biological clock triggers our internal “alarm”.
On the basis of what we have seen in the two systems described above, a complex neural network and stimulation / inhibition pathways regulates the passage from wakefulness to sleep, “turning off” or “turning on” some areas of the brain; in particular, mediators such as acetylcholine, dopamine, noradrenaline, serotonin, orexin, glutamine and histamine are involved in this process. These paths are integrated with each other and each can compensate, within certain limits, the shortcomings of another, helping to regulate the sleep-wake mechanism through a “flip / flop” process similar to the one of electrical switches.
DISEASES RELATED TO SLEEP DISORDERS
Lack of sleep can lead to serious health problems, and the link between sleep disturbances and the development of chronic diseases has grown significantly in recent years. According to the Center for Disease Control (CDC), such conditions include diabetes, cardiovascular disease, obesity and depression.
Insomnia (difficulty falling asleep or sleeping without interruption throughout the night), in particular, can increase the risk of developing these conditions and lead to symptoms such as tiredness, sleepiness, concentration and memory impairment, as well as anxiety and disturbances mood. An alarming figure if you consider that between 50 and 70 million people in the United States suffer from sleep disorders , which impede health and the ability to perform daily functions.
Research has shown that lack of sleep is linked to the development of type 2 diabetes as it changes the way the body releases glucose into the blood . Adults who sleep no more than five hours a night generally have a higher risk of having diabetes. Additionally, according to research, increasing sleep quality may be an effective way to improve blood sugar control in people with type 2 diabetes.
People with sleep disorders are more likely to suffer from coronary heart disease, stroke, irregular heartbeat, and high blood pressure . Indeed, a single sleepless night can raise blood pressure levels in hypertensive individuals the next morning. There is also evidence that sleep apnea and heart disease are linked. Sleep apnea is an arrest of breathing during sleep lasting at least 10 seconds or more, which can lead the sufferer to abruptly wake up several times during the night.
Those who do not sleep for long periods of time or have trouble sleeping through the night experience metabolic changes that could lead to obesity . While we sleep, our body secretes hormones that regulate appetite, metabolism and glucose processing, the balance of which can be upset if we don’t get the right amount of sleep.
For example, sleeping little leads to an increase in the production of cortisol (the stress hormone) and in the secretion of insulin after a meal. Insulin regulates glucose processing and promotes fat storage – higher levels of this hormone are associated with weight gain, the number one risk factor in developing diabetes.
Lack of sleep can also cause low levels of leptin, a hormone that signals the brain that the body has had enough food, as well as higher levels of ghrelin, a substance that stimulates appetite. A hormonal imbalance of this type can cause food cravings even when an adequate number of calories have been taken. Not to mention, finally, that poor sleep quality inevitably affects our energy load, leaving us too tired to practice healthy physical exercise.
Bad sleep can make people irritable and moody, and it is conceivable that chronic sleep disturbances can lead to long-term mood swings. Those who sleep infrequently report feeling stressed (do you remember the increase in cortisol as it affects stress?), angry and less optimistic than usual. All of this can lead people to develop forms of depression, which, however, can decrease once sleep is properly restored: when developing a treatment plan for depression, it is imperative to consider the quality of sleep.
All of this has an inevitable impact on our health and it is no coincidence that people who sleep too little have a shorter life expectancy than those who rest properly. But how many hours a day do you need to sleep to have a restful sleep?
Well, as we saw earlier it depends on person to person. In general, however, age is the variable that best explains the individual differences in the duration and quality of sleep . Newborns need about 16-18 hours of sleep, spread over several episodes throughout the day and night. From first to second infancy, the sleep-wake cycle is progressively organized into a single episode of nocturnal sleep, lasting about 9 hours. Thereafter, the total sleep period gradually decreases, stabilizing in adulthood at an average of 7 – 8.5 hours per night .
MONITORING YOUR SLEEP: THE SLEEP TRACKERS
Nowadays we don’t necessarily need an advanced diagnostic test such as polysomnography to perform a sleep analysis. The technological evolution of smartwatches and other wearable devices (smart bands, rings, helmets, mattress mats) has made it possible to monitor a large number of data relating to the quality of our sleep.
Most of these devices are able to reconstruct our hypnogram starting from the heartbeat and the body movements that are produced during sleep; some also have an oximeter available to measure the amount of oxygen in the blood, whose peaks during the night can signal the presence of sleep apnea. In this way, devices produced by Fitbit, Oura, Garmin, Withings, Apple, Samsung, Xiaomi, Huawei and Whoop allow you to see the number of total, light and deep sleep hours, the heart rate at rest and the arterial saturation at night, also defining a sleep quality score that allows us to understand if it is improving or worsening over time.
It is interesting to mention separately the Withings Sleep Analyzer, an intelligent mat that is positioned under the bed (see figure 4), which allows to accurately analyze the quality of sleep and the presence of sleep apnea starting from movements data collected by sensors that are in close contact with the mattress. It also allows you to analyze snoring by highlighting the time in which the person is affected by the acoustic phenomenon during the night.
Also, to conclude, we report a unique device of its kind: Dreem. This is a helmet with futuristic connotations (see figure 5) which is perhaps the closest on the market today to a polysomnograph: unlike Dreem, none of the previously illustrated instruments is able to record the brain activity of the subject who he is sleeping. All this is possible thanks to a EEG sensor (electroencephalography) which allows to measure the electrical activity of the brain. In addition, the device is equipped with an oximeter, motion sensor, sound level meter for snoring detection and a bone conductor to transmit sounds without using headphones: a real gem of technology!
At iCareX we believe that all of this data areextremely important and for that reason we are working to integrate it all into our iTwinSense mobile application. The latter allows you to connect countless sources to collect all information relating to sleep but also to many other activities recorded through these devices.
In particular, from November 2020, it will be possible to view all the data relating to the health categories of the main operating systems (Apple, Samsung, Huawei, etc.) in our APP. In doing so, we are committed to providing the patient with the ecosystem of his health data, which can be continuously updated and sent automatically and instantly to their doctor, who can monitor and analyze them according fro the patient’s well-being. And not only that: these data will be gradually integrated with all those present in the hospitals that will adopt our solution! Who hasn’t dreamed of having their entire medical history in digital format in a single application?
Our physicians have been equipped with a state-of-the-art data analysis platform, iTwinDiscover, which allows you to develop customized treatments by evaluating in advance the effects they will produce on the patient through the use of advanced clinical scenario analysis. With iTwinDiscover, the physician will have the opportunity to have a clear and complete view of sleep qulity data that the patient has collected from different sources: he will therefore be able to diagnose diseases related to his disorders in advance but, above all, help him to define a personalized sleep program based on your needs, illnesses and health features.
Our scenario analysis, in fact, allow us to make accurate predictions on the impacts that sleep can have on the patient’s biomarkers: what could happen to his heart rate if he sleeps too little or more than necessary? How might your blood sugar levels evolve over time? Could you gain weight and experience higher cholesterol levels? These are just some of the questions that the physician could find an answer to preserve and improve the patient’s health.
 Marcel Proust, À la recherche du temps perdu, First volume: Du côté de chez Swann
 Jeffrey C. Hall, Michael Rosbash and Michael W. Young, Nobel Prize in Medicine 2017
 National Institutes of Health. National Institutes of Health Sleep Disorders Research Plan
 Michael A. Grandner, Azizi Seixas, Safal Shetty and Sundeep Shenoy (2016), Sleep Duration and Diabetes Risk: Population Trends and Potential Mechanisms
 Michiaki Nagai, Satoshi Hoshide and Kazuomi Kario (2010), Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature
 S Taheri (2006), The link between short sleep duration and obesity: we should recommend more sleep to prevent obesity
 Carskadon e Dement (2000)
 Morin e Espie (2004)