Sleep - What Sleep Is, How Sleep Works, Why Do We Sleep, How Sleep Can Go Wrong


HOW SLEEP WORKS
CIRCADIAN RHYTHMS

Human circadian rhythms are regulated by an internal biological clock in the brain
Human circadian rhythms are regulated by an internal biological clock in the brain
All animals and plants have a built-in circadian rhythm, which is adjusted or entrained to the environment by external cues, known as Zeitgebers (a German word meaning “time-givers"), the most important of which is daylight. The brain’s internal circadian clock (also known as the biological clock, body clock, circadian pacemaker, circadian system, circadian oscillator, etc), which is centred in the hypothalamus region of the basal forebrain, uses these Zeitgebers to naturally synchronize or reset itself each day to within just a few minutes of the Earth’s 24-hour rotation cycle (the word “circadian” comes from the Latin words meaning “about a day”).

Early research in the 1960s and 1970s (including some famous experiments in caves) had concluded that the natural “free-runningcircadian period of human beings was around 25 hours, not the expected 24 hours. However, later research (like that of Charles Czeisler et al in 1999) showed that these experiments were flawed, and that even the presence of electric lighting was enough to skew the results. It is now clear that, although individual circadian periods do vary - ranging between 23.5 and 24.5 hours in humans, dependent on variations in the person’s PER or period gene - they have a mean of around 24.2 hours, just slightly more than the Earth’s rotation. About 25% of people have a circadian period which is slightly less than the 24-hour day, and 75% have a circadian period slightly more than 24 hours.

The brain’s circadian clock regulates sleeping and feeding patterns, alertness, core body temperature, brain wave activity, hormone production, regulation of glucose and insulin levels, urine production, cell regeneration, and many other biological activities. The most important hormones affected by the circadian clock, at least insofar as they affect sleep, are melatonin (which is produced in the pineal gland in the brain, and which chemically causes drowsiness and lowers body temperature) and cortisol (produced in the adrenal gland, and used to form glucose or blood sugar and to enable anti-stress and anti-inflammatory functions in the body).

Growth hormone, essential to the repair and restoration processes of the body, is also secreted during sleep, particularly during deep non-REM sleep, as are other hormones like testosterone. Thyrotropin (or thyroid-stimulating hormone), on the other hand, is actively inhibited or suppressed during sleep. However, unlike melatonin and cortisol (which are almost entirely dependent on the circadian clock, regardless of whether an individual actually sleeps or not), these hormonal effects appear to be regulated by actual sleep and not by circadian rhythms per se.

The human biological circadian clock (image from Wikipedia)
The human biological circadian clock (image from Wikipedia)

Humans are diurnal animals, naturally active during the daytime, and our circadian rhythms reflect this. Generally speaking, for sleep to occur in the “right” part of the circadian cycle, the time of minimum core body temperature and maximum melatonin concentration should occur towards the end of the sleep period. As a rough guide, core temperature usually reaches its minimum around 4:30-5:00am in the morning in human adults, and melatonin (normally completely absent during daylight hours) typically begins to be produced around 8:00-9:00pm at night and stops around 7:00-8:00am in the morning (see diagram below). The deepest tendency to sleepiness occurs in the middle of the night, around 2:00-3:00am, along with a shorter and shallower period of sleepiness (often referred to as the “post-lunch dip”) about twelve hours later, around 2:00-3:00pm in the afternoon.

Melatonin production (image by Luke Mastin)
Melatonin production (image by Luke Mastin)

Physically, the circadian clock is located in the suprachiasmatic nucleus (SCN) in the hypothalamus of the brain, one in each brain hemisphere. The SCN is a tiny pinhead-sized area, containing just 20,000 or so very small neurons, but it has the responsibility for sending signals to several other parts of the brain to regulate the daily sleep-wake cycle, body temperature, hormone production and other functions. In fact, the individual neurons that make up the SCN have been found to exhibit a near-24-hour rhythm of activity, suggesting that the clock mechanism actually works on a sub-cellular level. When dissociated from the SCN, the individual cells follow their own intrinsic 24-hour rhythms, but, when incorporated into the SCN, they all fire in synchrony. In experiments on mice where the SCN is completely removed, the mice (which are normally much more active during the nighttime and sleep more during the day) show little or no preference for their active time and sleep time, and their activity is sporadic and apparently random throughout the day and night.

The body's circadian clock is located in the suprachiasmatic nucleus (SCN) in the hypothalamus (image from Psychology Continuing Education)
The body's circadian clock is located in the suprachiasmatic nucleus (SCN) in the hypothalamus (image from Psychology Continuing Education )

The circadian clock checks its accuracy each day using external Zeitgebers, principally the light-dark cycle. Exposure to natural daylight stimulates a nerve pathway from special photoreceptive ganglion cells in the retina of the eye, cells that are totally separate from the rods and cones our eyes use to generate our everyday image of the world. These cells contain a unique light-sensitive pigment called melanopsin, and are most sensitive to short wavelength “blue light”. Even many blind people can respond to these light-dark cues, as the photoreceptive cells in their eyes can usually recognize daylight, even through closed eyelids. The light-dark signals are sent via the optic nerve to the suprachiasmatic nucleus, which uses them to reset its own circadian clock each day.

The biological clock does not actually require light to function, and the circadian cycle persists quite accurately even when individuals are completely cut off from daylight. The light-dark cycle (in concert with other Zeitgebers like meals, ambient temperature, etc), merely acts as an external cue to resynchronize or entrain the timing of biological rhythms, and to prevent small timing errors from accumulating. Without this important check, the circadian system can become seriously unbalanced. For example, the much dimmer illumination of artificial lights is not usually sufficient to trigger this reset of the circadian clock, which is why night shift workers never really fully adapt to their unnatural sleep patterns (see the section on Shift Work). It has been shown that simply increasing day-time lighting intensity in workplaces and care homes for the elderly can significantly improve their sleep regimes, reduce cognitive decline and improve mood disorders.

The irregular sleep patterns of newborn babies occur because circadian rhythms take some to develop, and most infants have established a more or less regular sleep-wake cycle by three to six months of age. Interestingly, some Arctic animals only show evidence of circadian rhythms during the times of year with more or less regular sunrises and sunsets (spring and fall), while others have been shown even to maintain their circadian rhythms through extended periods of sunlight or darkness. For people living in far northern locations, other Zeitgebers such as meal times, alarm times, house lights, etc, become relatively more important, so that people living in Alaska or northern Sweden can still function more or less normally during the long darkness of winter.

As well as regulating hormone production, body temperature, etc, the SCN also sends out an alerting pulse throughout the day (sometimes referred to as the circadian alerting system) which counteracts the increasing homeostatic sleep pressure. These alerting pulses from the SCN reach their peak about 2-3 hours before one's habitual bedtime (sometimes referred to as the "wake maintenance zone"), which serves to offset the homeostatic drive that has been continually accumulating throughout waking hours, allowing for continued alertness late into the evening. As the evening progresses, though, the SCN’s alerting pulses start to weaken, melatonin production in the pineal gland increases (also under the direction of the SCN), and the “sleep gate” (also known as the primary sleepiness zone or sleep onset zone) opens, and the urge to sleep increases dramatically.

The body has other secondary or peripheral circadian clocks, located in various organs, but all are influenced by the central circadian clock in the suprachiasmatic nucleus (image from Science Direct)
The body has other secondary or peripheral circadian clocks, located in various organs, but all are influenced by the central circadian clock in the suprachiasmatic nucleus (image from Science Direct)

There are also other secondary or peripheral biological clocks throughout the body, such as in the liver, heart, pancreas, kidneys, lungs, intestines, and even in the skin and lymphocytes, all of which show natural daily oscillations. These organs are largely entrained independently by factors like the timing of meals, ambient temperatures, etc, rather than by the light-dark cycle, but the central coordination and synchronization of these secondary body clocks is still carried out by the suprachiasmatic nuclei. The main circadian system in the SCN in turn receives multiple feedbacks from these various organs, in a complex system of reciprocal interactions. Chronobiology, the relatively new science of timing medical attention to various organisms of the body depending on the most propitious time of day for those particular organs, has shown very good results in improving the effectiveness of treatments.

In recent years, particular genes have been identified as being involved in the circadian cycle, and it is no surprise to find that these genes are particularly active within the cells of the suprachiasmatic nuclei, as well as within the cells of other body tissues. Scientists now estimate than between 8% and 15% of the genes in the human body operate on a 24-hour cycle. The very similar sleep architecture of closely-related individuals (especially identical twins) demonstrates the strong genetic element in sleep, and certain genes - including CLOCK, BMAL, PER, TIM and CRY, among others - have been specifically identified as being involved in the sleep process, although the exact mechanism through which they regulate sleep is still being explored. Mutations in these genes have been associated with several different sleep disorders.

Circadian rhythms may be adjusted by up to two hours or so either way according to an individual’s chronotype. Some people (often known as “larks” or morning people) tend to wake up early and are most alert during the first part of the day. Others (“night owls” or evening people) are most alert in the late evening and prefer to go to bed late. By some estimates, as many as 20% of people fall into one of these two categories. In these people, the timing of their circadian period is shifted completely (an effect that is at least partly encoded in their genes), so that morning people wake at a later stage in their circadian day, and are therefore much more alert on waking; evening people, on the other hand, wake too early in their circadian day, and so are less alert and perform poorly in the morning. Typically, this variation is limited to a couple of hours earlier or later than the average; those with extreme body clocks may have difficulty participating in normal work, school or social activities, and are considered to suffer from circadian rhythm sleep disorder (see the section on Sleep Disorders).