THE BRAIN FROM TOP TO BOTTOM

The Sleep/ Dream/ Wake Cycle

Our Biological Clocks

In the annals of chronobiology, the names of two pioneers crop up continually: Colin Pittendrigh, who discovered the circadian clock in fruit flies and described the common characteristics of circadian clocks, and Jurgen Aschoff, who uncovered the physiological mechanisms that regulate circadian rhythms in birds and mammals, including humans.

Around 1860, French physiologist Claude Bernard demonstrated a major principle that governs living organisms, which he named homeostasis. Bernard defined homeostasis as the organism’s ability to maintain relative stability in the various components of its internal environment, despite the constant variations in its external environment.

Chronobiology has since demonstrated that homeostasis is very much a dynamic process—by virtue not only of its responses to variations in external environmental factors, but also of the body’s many internal cycles. Some authors, such as neurologist Antonio Damasio, have even proposed referring to homeodynamic processes rather than homeostatic ones, to emphasize that there is not not just one form of homeostasis, but several different ones, varying with the time of day, the month, and even the year.

CHRONOBIOLOGY

The research field now known as chronobiology deals with the body’s biological rhythms: the way that it generates its physiological oscillations and keeps its various systems synchronized.

Ever since the first findings suggesting that cycles of varying length occur in the human body, scientists’ understanding of chronobiology has rapidly grown more complex. They quickly realized that daylight alternating with darkness was not the source of human circadian rhythms, but simply the means by which a truly endogenous central biological clock within the body is kept synchronized with the hours of day and night. This central clock that is synchronized by daylight is located in the suprachiasmatic nuclei of the brain.

Scientists also soon discovered the importance of this cyclicity in most of the body’s major systems. Whatever physiological variables researchers measured—such as cell metabolism, body temperature, or the secretion of various hormones—each seemed to fluctuate in a cycle with its own specific peaks and troughs.

Many experiments have been conducted to uncover the subtle connections among these various rhythms. Some of the greatest insights have been provided by temporal-isolation experiments, in which subjects are completely isolated from the usual cues of alternating day and night, such as daylight and traffic noises. Numerous researchers have conducted such experiments, to examine questions such as whether, under such conditions, people continue to fall asleep at their usual time, or whether their activity cycle instead begins to run too fast or too slow.

The first temporal-isolation experiments were conducted in caves, where the temperature is naturally constant and where subjects can be completely isolated from the outside world. The first major finding from these experiments was that the subjects’ circadian rhythms persisted despite this isolation, which proved that all human beings have an “endogenous clock” inside their brains.

But these experiments also showed that this clock was not perfectly accurate: it lost a few minutes every day. In other words, the subjects’ natural endogenous circadian cycle was slightly longer than 24 hours, ranging from 24.2 to 25.5, depending on the study. This may not seem like much, but if someone’s cycle lasted 24.5 hours instead of exactly 24, then within 3 weeks, everything that he used to do in the daytime he would end up doing at night!

These temporal-isolation experiments date back quite some time. As early as 1938, Nathaniel Kleitman and his colleague Bruce Richardson spent 32 days in a cave in the U.S. state of Kentucky, deprived of all time cues. In 1962, the French researcher Michel Siffre spent two months in an underground glacier in France’s Maritime Alps. He was 23 years old at the time of this first experiment, and he spent two more long periods underground later in his career to measure how the absence of time cues affected his biological rhythms at various ages. The third time, in 2000, he was 61 years old and stayed underground with no time cues for 73 days (see box below).

Michel Siffre emerging from his third time-isolation experiment, in 2000 (AFP)

One of the most spectacular observations during these time-isolation experiments in caves, laboratories, and other settings is the way that subjects’ sleep-wake cycles shift relative to the actual alternation of day and night in the outside world. But as soon as the experiments are over, the subjects take only a few days to resynchronize their cycles to these external time cues. This shift and the return to normal are shown in the diagram below, where each line represents one day in a time-isolation experiment that lasted a month and a half. The solid part of each line represents the period when the subject was asleep, the dotted part represents the period when the subject was awake, and the triangle marks the time when the subject’s body temperature was lowest.

For the first 9 days of this experiment, the subject was exposed to the natural variations in ambient light and noises that characterize day and night. The first 9 lines of the diagram thus represent the control records for this experiment. For the next 25 days, the subject was cut off from all such cues as to the time of day and was left to operate according to his own endogenous rhythm. He continued to display a sleep-wake cycle, but it lengthened to about 25 hours. (After several weeks of such isolation, these cycles may get even longer—30 to 36 hours. For instance, a subject may stay awake for 20 hours, then sleep for 12, and feel completely fine.)

(Source: Adapted from Dement, 1976)

Another interesting phenomenon in these experiments is that in some cases, the time of lowest daily body temperature shifts from the end of the sleep period to the start of it. Thus time isolation may produce shifts not only in behavioural cycles (such as sleeping and waking) but in physiological cycles (such as that for body temperature) as well. This desynchronization is the likely source of the problems associated with jet lag.

In the last 11 days shown in the diagram, the subject was placed back in normal alternating conditions of daylight and darkness. The length of his cycle returned to normal, and the time that his body temperature was lowest shifted back toward the end of his periods of sleep.

The first “life out of time” study that clearly revealed an endogenous cycle of slightly more than 24 hours in human beings dates back to 1962. That year, French speleologist Michel Siffre, already legendary for his previous lengthy underground stays to experiment with isolation from time cues, spent two months in the Scarasson underground glacier in southern France. Siffre used a one-way communication system to tell his research team back on the surface the times that he woke, ate his meals, and went to sleep, but he received no information from them, and he had to estimate the passage of time on his own. When he emerged from underground, the actual date was September 17, 1962, but he thought it was only August 20, thus confirming how hard it had been for him to subjectively recognize how his biological cycle was lengthening.

At that time, nothing was yet known about the endogenous rhythms of the human body, so Siffre could not have been influenced by such knowledge in any way. In this sense, Siffre’s first long stay underground will always remain one of the “purest” time-isolation experiments. Soon after, as part of the Cold War, the Russians and Americans put their own subjects in closed bunkers to study their ability to live for extended periods in atomic-bomb shelters.

Michel Siffre conducted two more lengthy time-isolation experiments with himself as the subject. In 1972, he spent 205 days at the bottom of Midnight Cave in Del Rio, Texas. Even though this time, Siffre tended to make automatic corrections based on his memories of his 1962 experiment, when he emerged from the cave, his estimate of the date was still two months off!

Siffre conducted his third time-isolation experiment 37 years after the first. By then, he was 60 years old, and his plan was to study how his circadian rhythms had altered with age. He entered the Clamousse cave in southern France on November 30, 1999 and emerged over two months later, on February 14, 2000, thus having entered the new millennium all alone at the bottom of a cave.

Nowadays, many laboratories are equipped with rooms that are completely isolated from any fluctuations in light, sound, and temperature in the outside world. Volunteers can thus spend several weeks in temporal isolation, or in “forced desychronization”, a protocol in which they are subjected to days lasting less than or more than 24 hours. These specially equipped rooms make it far easier to monitor variations in the subjects’ physiological parameters during such experiments.