What a jolt it was the first time someone told us that sleep takes up a third of our life. By the age of 90, we will have spent an accumulated total of about 33 years sleeping. Suddenly sleep seems not so much sweet as it does demanding. But we slept on it, slept for many nights, stopped being shocked and got used to it. Not that there’s anything we can do about it. Just as we don’t have a choice about whether to eat or breathe. But in contrast to eating and breathing, our understanding of sleep is quite meager.
In fact, sleep – though it’s a basic biological process, daily and universal, one that has been studied for thousands of years – remains one of the great unsolved questions of the life sciences. What is the cause, the justification for this shutdown of body and mind, which suspends consciousness and abandons us to the mercies of our surroundings?
There are a few things we do know. For example, that sleep is not a situation of absence, in the sense that dark is an absence of light. Sleep is not nullity, it is not “death’s twin,” as Homer described it, and not a state in which our spirit is placed in God’s hands, as the shaharit prayers in Judaism have it (in which God is thanked, “for you have mercifully restored my soul within me”). We know that sleep is a condition involving many physiological occurrences in the brain; that it’s more necessary than food (one can fast for a few weeks but abstain from sleep for only a few days); and that it has many aspects.
More than 50 years ago, scientists who tracked brain waves (neural oscillations, which originate in electrical activity within the nerve cells) identified four distinct stages of sleep. In the first, the brain waves become a bit slower and higher than those recorded in wakefulness. We stop reacting to our surroundings, but if we’re shaken at this stage, we will wake up immediately and assert that we hadn’t been asleep at all. In the next stage, the waves intensify, but they become particularly intense in the third stage, known as “deep sleep.” Here the waves become very high and slow, dramatically different from the brain’s waking state. Finally, there is “dream sleep”: The brain waves are similar to those in wakefulness, and beneath the closed lids, rapid eye movement (hence the name “REM”) is discernible. Eighty percent of people who are wakened from this state report having dreamt.
Several other facts are also known. The stages appear in the same order each time we sleep, and cyclically. Each cycle lasts about an hour and a half, but the length of the stages changes during the night: In the beginning, the deep-sleep stage is the longest, but toward morning the dream sleep becomes longer. But what exactly happens during the different stages, what they represent and why we can’t do without them are questions to which scientists are only starting to find answers.
“Until recently, we measured brain waves by means of electrodes that were attached to the sleeping person’s skull – a process known as EEG [electroencephalogram]. But as more technological advances allow us to look deep into the brain, our understanding increases,” says Dr. Yuval Nir, from the physiology and pharmacology department of the Sackler Faculty of Medicine and the Sagol School of Neuroscience at Tel Aviv University, and the Center for Brain Function at Ichilov Hospital in Tel Aviv. “The new discoveries are challenging our old conceptions about sleep in particular and the brain in general.”
Everyone needs sleep, but some need it less than others. People tend to admire those who make do with less sleep, even to attribute a certain superiority to them. In Martin Buber’s “The Hidden Light,” there’s a story about Rabbi Isaac Meir from Gur, who was asked by his wife why he slept so little. He replied by asking her: Why did your father marry you off to me? Because I was a prodigy. And what is the nature of a prodigy? One who learns in two hours what takes someone else an entire day. In the same way, I sleep in two hours what another sleeps the whole night. Shimon Peres, too, enjoyed the glory reserved for those who manage on very little sleep, and Margaret Thatcher, the “Iron Lady,” said that “sleep is for wimps.”
What makes these people supposedly superior?
Nir: “Well, for Margaret Thatcher’s information, sleep is a general need, not only for wimps – but there are definitely big differences in the amount of sleep people need, and this has a genetic component. What differentiates people who get along with brief sleep from others is the deep-sleep stage. They compensate for sleeping less by producing higher waves during the deep-sleep stage.”
Generally, in discussions of sleep, people talk about the REM stage, but you focus on the deep-sleep stage. Why?
“In the 1980s, the primary importance of sleep was identified with the REM stage... But then people began using antidepressants, which drastically reduce the REM stage – and, amazingly, no great influence on functioning was observed.
“In addition, scientists started to study sleep among more simple creatures, too, such as fish and flies, and discovered that they don’t have a REM stage. It turned out that this stage exists only in mammals and in a small number of birds and reptiles. So, with all due respect for dreaming, it’s clear that the importance of sleep goes far beyond that stage. The deep-sleep stage exists in all animals, so obviously it possesses a critical significance.
“When a person catches up on sleep after missing out on it, his brain seems to calculate how much is missing and then makes up the difference, but less in the number of hours of sleep than in depth of sleep. A person who is catching up on his sleep, sleeps more deeply and is harder to wake up. The waves in the deep-sleep stage are slower and higher.
“Most studies are looking for a way to deepen the sleep of people who suffer from sleeping problems – of whom, as we know, there are a great many. Researchers try to attach electrodes to the skull of a sleeping person to ‘listen’ to the brain waves and, at the appropriate time, send a weak stimulus that will make the waves reverberate and make them higher. These studies are still in their initial phases, but if they come to fruition, they might be of use not only to people with sleeping problems, but also to those who simply want to reduce the amount of time spent in bed and sleep just four hours a night instead of eight.”
Asleep while awake
Until not long ago, textbooks described the state of the brain in the deep-sleep stage as resembling a sea whose large, slow waves rise and fall together, in perfect harmony, in contrast to the other stages, where the waves toss about in all directions. But then Nir embarked on an innovative study at the University of Wisconsin, where he was doing a postdoctoral fellowship, working with Prof. Giulio Tononi, from the university’s Center for Sleep and Consciousness, one of the world’s leading sleep experts. In collaboration with Prof. Itzhak Fried, a neurosurgeon and brain researcher at UCLA and at Tel Aviv’s Ichilov Hospital, they set out to penetrate the sleeping brain and measure its activity from within, not only from outside. Fried treats epilepsy patients by means of electrodes that are implanted in their brain and regulate the attacks, and at the same time uses the electrodes to examine the brain’s ongoing activity.
Using the technology to examine the sleeping brain, the researchers discovered that the notion of perfect synchronization that had been attributed to the deep-sleep stage was simply incorrect. In this stage, too, they found that frenetic activity occurs in different regions – without coordination between them.
“The classic tests create a false impression of uniformity,” explains Nir, “because in EEG the electrodes are placed outside the skull and record the global, average activity of the brain. The electrode implants allowed us to record the activity of solitary neurons that exist in separate, mutually remote regions of the brain.”
It’s like recording individual people by means of a microphone aimed at them directly, as opposed to recording a large audience using a microphone suspended above them.
“Exactly. And what’s interesting is that in the wake of the improved separation ability, we discovered that wakefulness, too, and not only sleep, is a kind of false show of uniformity. When we deprived rats of sleep and examined their tired brains, we found, in various regions of the brain, the large waves that characterize deep sleep – even though they were awake!”
So sleep started to invade wakefulness.
“Exactly. And then we decided to examine what happens to the areas of the brain that are ‘conquered’ by sleep. Do the deep-sleep waves interfere with the work they do – with the hearing region that deciphers sounds, with the relevant region for identifying faces, and the like? To examine this, we showed sleep-deficient people pictures – of the Eiffel Tower or of famous people – and asked them to say whether a person appears in them or not. People who have slept do the task quickly and efficiently. The sleep-deficient people hesitated. It sometimes took them a few seconds to reply, and when we examined their brains, we discovered that high, slow waves appeared in the relevant part of their brain, like the ones at the start of sleeping, and that the neurons there responded slowly and more weakly.”
What does this say about the boundaries between wakefulness and sleep? That they are blurred, fluid, that here too we can talk about a spectrum?
“The level of a person’s wakefulness-drowsiness can sometimes be a matter of life and death. We all know that it takes a tired driver longer to hit the brake when he sees a figure bursting into his field of vision. Our research shows that the slowdown occurs not only at the level of decision making and motor response, but already at the level of vision and recognition. Twenty percent of road accidents are caused by the driver’s tiredness – similar to the proportion of accidents caused by alcohol consumption. Yet there are no laws against driving while under the influence of weariness.”
Perhaps because we don’t have the ability to measure weariness, the way we can test for alcohol with the Breathalyzer.
“Accordingly, what we’re trying to do now, based on the latest findings, is to develop a way to identify the large and slow waves when they invade the brain, and determine a certain threshold beyond which driving is dangerous and therefore should be forbidden.”
Self-driving cars will solve that problem.
“We still have doctors, especially residents, who are awake for countless hours, flight controllers and others who do night shifts in life-and-death jobs. The commissions of inquiry that were established after the Exxon Valdez oil-spill disaster and after the crash of the Challenger space shuttle determined that one of the reasons for these monumental accidents was the fatigue among those responsible. There’s no doubt that credible measurement is necessary, and a threshold value set beyond which people must be forbidden from doing certain jobs.”
According to these studies, tiredness appears to be a kind of dimmer that dulls the waking brain, region after region, until a condition of sleep sets in. At the same time, medicine recognizes narcolepsy: a sleep disorder that causes people to enter into a sleep state suddenly and uncontrollably, as though some inner switch had been turned off.
Studies have shown that narcolepsy affects brain neurons that produce substances called orexins. To examine the connection between orexins and sleep, scientists engineered mice that lacked these neurons and showed that they fell asleep suddenly. Using engineered mice in which the neurons could be activated from the outside, the researchers showed that the mice awoke seconds after the orexins were secreted. Clearly, then, the orexins can throw the metaphorical switch.
So what is it that activates sleep, a dimmer or a switch?
“It’s apparently a combination. When the body is tired, the biochemistry begins to change, the brain waves change gradually and everything starts to work more and more slowly, until a certain threshold is reached, a kind of switch, beyond which the brain enters a completely different mode of activity: sleep. It’s interesting that we intuitively think that wakefulness is the body’s default state and sleep is the condition that needs to be activated, but in my view, it’s the opposite. The basic condition is sleep, and a great many substances, like the orexins, are activated vigorously to keep the brain awake.”
How is tiredness created? Is it an accumulation of waste substances that slow down the system, or a dilution of the substances that drive it?
“Again it’s a mixed bag: Mechanisms of both kinds exist. We know several molecules that are ‘responsible’ for tiredness, such as adenosine, which is a product of cellular activity and thus continually accumulates in conjunction with that activity. It’s known that when adenosine binds to its distinctive receptors, it ‘signals’ tiredness to the brain. Studies have shown that when adenosine or its receptors are manipulated, the degree of wakefulness changes.”
Is there a connection with coffee?
“Yes! Caffeine is the ‘chemical rival’ of adenosine – that is, it competes with it over binding to the receptors. When caffeine binds to the receptors, it prevents adenosine from binding to them and interferes with the course of events that signal tiredness to the brain, and therefore it wakes us up.”
But it’s impossible to keep sleep at bay indefinitely. At some stage, even after many cups of coffee, we are compelled to sleep. So we come to the million-sheep question: Why do we sleep?
“There are three main theories,” says Nir, “and where several theories exist, it’s very probable that we simply don’t know the answer. It’s also very possible that there is no one reason or one advantage for sleep, but a combination of reasons and advantages.
“The first theory attributes an adaptational role to sleep. According to this theory, if an animal doesn’t have to do anything specific, it’s preferable for it to sleep. If it’s sated, isn’t occupied with reproduction and doesn’t have to defend itself – there’s no reason for it to roam about and endanger itself. It could, for example, step on a thorn and die of infection, or fall into a pit. That’s why most animals sleep at night and predators sleep far more than their prey. A lion that has caught prey remains sated for a long period, so it can sleep 20 hours a day. But an antelope, which has to look for food all the time and watch out for predators, will sleep only some four hours a day. In other words, according to the first theory, sleep reduces the interaction of animals with their surroundings to the essential minimum, to keep them out of trouble.”
As the mother of a friend of mine used to say: Only people who do nothing make no mistakes. Sometimes it’s better not to do anything.
“Something like that. There are several arguments against this theory, one of them being that when polar bears come out of hibernation, the first thing they do is go to sleep.”
“It’s true, and on top of that, the bears wake up a few times from their hibernation – only to go back to sleep. That means that winter hibernation and sleep are two different biological processes and also that sleep can’t be summed up as only being a means of avoidance. Moreover, during sleep, the brain is too lively to reduce the role of sleep to merely being adaptation to the environment.”
The second theory talks about sleep as an active process of rehabilitation. We all know that without sleep our concentration suffers, our cognitive abilities deteriorate and we’re in a lousy mood, but that these elements get back on track after a sound sleep. Something happens during sleep that rehabilitates the brain and restores it to normal activity.
“When we’re awake, our brain neurons are very active,” Nir notes, “which means that they are producing plenty of waste materials. In the rest of the body, the lymphatic system drains part of the wastes that accumulate between the cells, but the lymphatic system doesn’t reach the brain.”
The brain has a different sanitation solution. The waste material in the brain is removed via the liquid in which the brain itself is immersed, which turns out to be a night worker. Scans of mice brains have shown that during sleep, the cells adjacent to the neurons (the glia cells) organize so that the fluid can stream between them and wash the brain. Why does this happen only during sleep? “Maybe for the same reason that sanitation workers in Paris wash down the streets at 4 A.M.,” Nir suggests, with a smile. “So as not to disrupt everyday activity.”
He adds, “Various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, are related to the accumulation of waste between brain neurons. Scientists who followed beta amyloids – the proteins whose accumulation is a salient symptom of Alzheimer’s – discovered that they are removed effectively precisely during sleep and not in wakefulness.”
So lack of sleep can cause or induce Alzheimer’s?
“Definitely. There are many studies that show a link between lack of sleep or little sleep and the development of Alzheimer’s and other diseases: diabetes, high blood pressure, stroke and even progression of cancer.”
That’s pretty stressful, one must admit, and might make it difficult to fall sleep.
“All I am saying is that in the modern age we pay a great deal of attention to physical activity and nourishment, but still forgo sound sleep too easily.”
Learning and memory
The third theory that seeks to explain the necessity of sleep attributes to it a central role in learning and memory. It’s clear that after a good night’s sleep the ability to learn and to draw on the memory are at their peak. However, this theory maintains that sleep is not only a prior condition for efficient learning during wakefulness, but also that a critical stage in the learning process takes place during sleep.
Nir: “During the day, we learn countless things, far more than we are aware of. The brain absorbs numerous bits of information – figures and sounds, objects and smells – and at any given moment it needs to characterize them, determine the relations between them and compare them to older items of information already stored in the memory. The information has to be filtered, deciphered, classified and understood, and this processing – the theory says – is done principally during sleep.
“For example,” he continues, “take the case of a boy who moves with his family to new surroundings. I’m speaking from experience, of course – the experience of my children, who were with me during my post-doc abroad. In addition to a foreign language, the child becomes acquainted with new rules and alignments of forces different from what he knew previously. At the end of the school day, he comes home wiped out and falls asleep immediately. During sleep, he processes the new information, and the synapses between the neurons reorganize in order to support and internalize the fresh memories. In this way, he starts to understand his new world.”
That’s a good story. Does it have a leg to stand on?
“Absolutely. The first behavioral study was conducted as early as 1924, and it showed that associations between pairs of words that are learned in the evening are preserved better in the morning after a night of sleep than after a sleepless night. In other words, something good happened to learning and memory during sleep. Since then, the studies have been broadened. A few years ago, it was shown that rat neurons that were active when the rat learned how to navigate a maze also acted when the animal slept – as though it were awake and engaged in navigating. The researchers termed the phenomenon ‘replay,’ and when they disturbed the [initial] ‘play,’ the rats had difficulty in finding their way through the maze.”
Why is this disconnect from the surroundings necessary?
“During wakefulness, neural binding changes in the course of interaction with one’s surroundings. Sleep blocks the reception of new data, and thus allows all the resources to be diverted to processing the existing information.”
Like an end-of-year inventory: The store is closed to customers so the merchandise can be organized and the stock analyzed without interruption.
“That’s an excellent analogy. It’s impossible to get a reliable picture of the situation and do the ‘real accounts’ when you have to deal with new stimuli coming in, and impossible to organize the stock when it keeps changing.”
What is actually processed and organized during sleep?
“The new information in relation to the old information. In a process called ‘memory consolidation,’ the new information that has just been acquired becomes an integral part of the information that already exists in the memory. From being fragile and short-term, it becomes a long-term memory that is relatively durable. Studies indicate that this process involves a transition from one physical region in the brain – the hippocampus – to other regions in the cerebral cortex, and this apparently takes place during sleep.”
The theory of the consolidation of memory during sleep is quite old, but one of its intriguing new versions belongs to Giulio Tononi. He postulates that sleep is indeed important to learning, but not necessarily because it allows the acquisition of new memories. On the contrary: It induces their being forgotten.
“We are constantly encountering new things,” Nir explains, “and it’s impossible for everything to be burned into our brain perpetually. If we remember continuously, the system will reach saturation, and we won’t be able to learn anything else. The brain needs to be selective and also be able to distinguish between wheat and chaff. Tononi offers the example of a new acquaintance. Let’s say that in the morning you met someone and spent a whole day with him. Until evening, large numbers of the neurons in your brain will be occupied learning about the new acquaintance: face, voice, opinions and a million other things. At the moment, he’s the hottest thing in the area. However, it isn’t a good idea to diminish the value of the veteran neurons, which by chance were less active that day, for the benefit of the new event. If we do, we’ll always remember only new acquaintances and forget the old ones.”
According to Tononi, that’s the importance of the brain’s disconnect from the surroundings during sleep. “The disconnect,” Nir continues, “frees the brain from the tyranny of the present, from a situation in which memories of the latest events dominate the information the brain has acquired throughout life, in favor of a comprehensive view of all memories.”
When we learn something new, he notes, “certain connections between neurons are strengthened, so they are more easily activated. Tononi’s principal argument is that the strengthening of these binds occurs mainly when the animal is awake – it encounters new situations and pays heed to significant events – whereas in sleep they are actually weakened. It’s selective weakening, carried out by a mechanism that ‘lowers the volume’ of all the binds, so that only the strongest, meaning the most significant, remain. The new binds, superficial and weak, are weakened further and even disappear.
“The role of sleep,” Nir says, summing up Tononi’s ideas, “is to control the learning that takes place during wakefulness, to temper the changes that took place during the day, and in general to preserve the status quo.”
Like an old aunt, who tries to dampen momentary enthusiasm and youthful mischievousness.
“Yes, sleep is definitely in favor of stability. Learning new things is excellent, but there’s no need to overdo it. Not every marginal event is meant to leave an imprint on the neural cycles. As a former Haifa resident, I will evoke the image of Mount Carmel after the great fire there to describe the mechanism. When the pines burned, masses of seeds fell to the ground, and most of them were washed into the valley below by the next rain. But there were seeds that penetrated the soil, which the rain did not wash away, but rather watered and helped them bud.
“Sleep resembles rain in the sense that what happened during the day but was not implanted deeply, is removed, and what was absorbed better is strengthened even more. The weakening of the binds during sleep saves the brain’s limited resources – substances and energy – and also preserves the ability of the neural cycles to create new memories without reaching over-saturation.”
Without going into details, is there evidence of a weakening of the binds during sleep?
“There’s a variety of evidence. For example, the number of those molecules that determine the strength of the inter-neural bind increases during the day and returns to a base level after sleep. The inner area of the spaces between the neurons, which mediates the communication between them, diminishes after sleep, and so on. Personally, I believe that a mechanism exists in the cell that marks the neurons that have undergone something important, so that they will not be weakened or erased, perhaps like the cellular mechanism that marks proteins destined for degradation.”
That’s the mechanism for whose discovery Avram Hershko and Aharon Ciechanover (together with Irwin Rose) received the Nobel Prize in Chemistry, in 2004.
“Yes. They discovered that there is a specific protein, called ubiquitin, which attaches itself like a sticker to proteins that need to undergo degradation in the cell later. Possibly a similar mechanism exists that marks neural cycles that are connected with the learning of new and important content.”
Sleep as diagnosis
All researchers of the subject agree that sleep is important for learning and memory. Some think that this is the principal reason for sleep, others that it is only one of the reasons. “As I see it,” explains Nir, “the different theories are not mutually contradictory. Taken together, they can explain sleep, and it’s very possible that different roles developed in different periods of evolution. Simple creatures like jellyfish, for example, sleep because of the need for cellulose upkeep. Creatures that developed later ‘hitched a ride’ on the mechanism for additional needs, such as complex learning.”
How do you even define sleep in an animal like a jellyfish, which has no brain and whose brain waves thus cannot be measured?
“The question is even more acute. Brain waves, with whose help we define the stages of sleep in mammals, are created in the cerebral cortex. What do we do with animals that don’t have a region like that in the brain? The general definition of sleep is, a temporary condition of reduced reaction to one’s surroundings. For example, if you hit a certain worm, it will generally contract, but there are moments during the day when it won’t react. If you deprive the worm of those moments – the moments of sleep – you will interfere with its ability to contract during the rest of the time.
“By the way, scientists like to point out that all animals, without exception, sleep, but that should be qualified: all those that have been checked to date. For example, insects constitute the majority of creatures that populate the planet, but how many of them have been examined? We need to be honest and say that we are talking about fractions of a percent of all the animals on Earth.”
Without ruling on the main role of sleep, it’s clear that it has enormous benefits – otherwise its absence would not have such negative effects. In rats, prolonged lack of sleep leads to a failure in the immune system, in metabolism and in the control of body heat, and finally to death. Partial sleep deprivation is connected with the appearance of various diseases and disorders. It turns out that not only does lack of sleep lead to diseases, but the opposite is also true: Brain diseases are harmful to sleep – although that’s good news for medical diagnosis.
“Fascinatingly, an individual’s sleep pattern can attest to a neurological or psychiatric disorder,” Nir says, “and not only when the disorder is at its height, but years earlier. For example, a certain sleep disorder can indicate the onset of Parkinson’s seven to 15 years in the future.”
What is there in this particular sleep pattern?
“In healthy people, dream sleep is accompanied by muscle paralysis – some say that this is a mechanism to prevent the sleeping person from acting out his dreams. On the other hand, a person who is prone to Parkinson’s is not paralyzed in this stage, and he seemingly carries out the dream. Ninety percent of the people who display this pattern will develop Parkinson’s during their life.
“Alzheimer’s also has a distinctive sleep trait. The slow waves of the deep-sleep stage are lower and less coordinated, especially in the front part of the brain, and the more the disease progresses, the more prominent this trait becomes. That means that sleep has the potential to provide an objective gauge of the scope of a neurological disorder, instead of the patient’s subjective report or the behavioral tests on which neurologists rely today.
“Similarly, the brain’s activity during sleep can reveal how a stroke victim’s rehabilitation is progressing. A correlation has been found between the presence of slow sleep waves in the region surrounding the place of the damage, and the brain’s degree of recovery from the stroke. In mice, scientists have succeeded in also doing the opposite: By intensifying the slow waves of sleep in the stroke region, they accelerated recuperation from the damage.”
What about psychiatry – can disorders in that realm also be diagnosed through sleep patterns?
“Yes, and very impressively. Almost every brain-related illness has a representation in sleep. In schizophrenics, for example, there is a decrease in certain sleep waves that are focused on a specific site in the brain, and in a significant percentage of autistic people we find epileptic activity during sleep. Sleep disorders that are related to depression and bipolar disorder are seen long before the appearance of the regular symptoms, and given the fact that psychiatrists prescribe some powerful medications to their patients, it’s important to have objective indices that will ensure the accuracy of the diagnosis.”
Someone who was suffering from manic depression told me that in the years before the standard medications were developed, he discovered that his condition was eased if he didn’t sleep.
“Psychiatrists sometimes recommend sleep deprivation for people suffering from clinical depression, which is significant, particularly in the short term, for patients with suicidal tendencies, until the medications start to take effect, which usually takes several weeks. We have clues, but not yet full understanding of the mechanism.”
And, to conclude, what is the focus of your research at present?
“One of the most basic and most dramatic things in sleep is the severance from awareness of the world, so we think that a study of sleep can perhaps draw us closer to understanding consciousness. When the computer and I watch a movie, both of us are able to discern the location of the objects [on the screen], the direction of their movement and so on, but only I have a conscious perception of the stimuli in the movie. I alone have an experience, and it’s different from that of someone else who sees the movie and takes in the very same stimuli. That subjective experience – quale, as the philosophers call it – disappears when we plunge into deep, dreamless sleep. We are severed from the stimuli and the experiences, and that severance is the very heart of the sleep phenomenon.
“Nevertheless, there are stimuli that do succeed in entering our consciousness and awake us. So the interesting question is: How does the sleeping brain filter the stimuli, getting rid of some and admitting others? Infants go on sleeping even if a pot is dropped next to them, but adults, and old people in particular, wake up from every little thing. But it’s clear that not only the intensity of the stimulus influences the filtering, but also its nature.
“A person wakes up more easily at the sound of his name, in contrast to other words, and the mother of an infant will wake up at the sound of its specific crying, even when she is in the newborn nursery. For a stimulus to wake us up, it needs to be important to us – that is, connected to an experience that is meaningful for us. What we are trying to do, then, is identify patterns of brain reaction to the external world that are unique to a conscious situation during wakefulness, and disappear in sleep or under sedation. Those findings can help us understand, for example, how far people who are comatose or in a state of severe dementia understand what is happening around them in the world.”