The Nocturnal Brain Read online

  Yet many of the sleep disorders that you will read about in the following chapters, like other neurological disorders, represent lesions of the nervous system – largely microscopic, transient or genetically determined, but lesions nonetheless. They are nature’s experiments, giving us a window of opportunity to understand ourselves and help us identify how glitches in the brain’s control of sleep can result in this huge array of phenomena. We will see how lesions of the brain result in uncontrollable sleep attacks, vivid dreams, hallucinations, sleep paralysis and collapses during the day. How abnormalities in the brainstem cause us to act out our dreams, and how genetic factors influence our ability to walk, eat, have sex or even ride a motorbike in our sleep. How chemical abnormalities in the nervous system can give rise to odd and distressing sensations at night. How our genes influence our body clock. And how seizures arising in our sleep can generate terrifying nocturnal experiences. Thus these phenomena can tell us about how our brains regulate our sleep, and how various aspects of our sleep are controlled.

  Other patients in this book will illustrate how psychological or biological factors can influence sleep, causing debilitating insomnia, for instance, or sleep apnoea, where your breathing disrupts your sleep. One story in particular will demonstrate how a partner can have a huge impact on one’s sleep. But even in these cases, when the cause is not related to damage in the nervous system, sleep itself is lesioned, disrupted or altered in some way. Through these case studies we also gain insight into the role of normal sleep in maintaining the brain – memory, mood, vigilance – through the impact of sleep deprivation or interference. These individuals provide windows into our understanding of the importance of sleep in the maintenance of physical, psychological and neurological health.

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  I am eager to introduce you to my patients and their stories, but before I do so, please forgive me a brief but important digression. To appreciate abnormal sleep, it is helpful to understand normal sleep. As we pass through life, our sleep changes, both in quantity and in quality. A newborn will sleep for two-thirds of the day, but by the time we are adults, we tend to sleep between roughly six and a half and eight and a half hours a night. Sleep is not a static state, however, and there are actually multiple stages involved.

  As we first drift off, we enter into Stage 1 sleep, also known as drowsiness. The brain exhibits a quietening of normal waking electrical activity and the eyes slowly roll from side to side. As sleep progresses, we enter into Stage 2 sleep – light sleep – when the brain activity slows further. When we record the brainwaves during this stage, features called sleep spindles and K-complexes – transient alterations in the background brainwave rhythm not evident in wakefulness – become visible. By the time we reach Stage 3 sleep – deep sleep – usually within about thirty minutes or so of drifting off, the brainwaves slow considerably but increase in size. This stage is therefore sometimes referred to as ‘slow-wave’ sleep. Stages 1 to 3 are considered non-rapid eye movement (non-REM) sleep, and it is only after sixty to seventy-five minutes or so that we enter into rapid eye movement (REM) sleep.

  As we will see, in REM sleep, the eyes dart back and forth rapidly, the brainwaves look to be highly active – a little like being awake – and it is in this stage of sleep that we most obviously dream. As adults, over the course of the night we cycle through these various stages of sleep, usually four or five times, with the majority of deep, Stage 3 sleep in the first half of the night, and the majority of REM sleep in the second half.

  As we age, the proportions of these various stages of sleep change. As newborns, we spend about half of our sleep in REM sleep, while in adults this ranges from 15–25 per cent, gradually falling as we approach old age. The proportion of Stage 3 sleep also changes, being roughly 15–25 per cent in adulthood, but dropping a little in the elderly, usually replaced by Stage 1 and 2 sleep. As we get older, the amount of wakefulness at night (very brief awakenings) increases too. As I will go on to show you, a complex system of brain nuclei, brain circuits and neurotransmitters regulate this biological process, controlling the initiation and termination of sleep, as well as the switch between non-REM and REM sleep.

  There are two further processes that are important to grasp, since these mechanisms control the drive to sleep. The first is the homeostatic mechanism.

  As anyone will know, the longer you have been awake, the stronger your drive to sleep. With prolonged wakefulness, levels of certain neurotransmitters that promote sleep build up, increasing sleepiness and thus promoting sleep onset. But the second potent force is that of the circadian clock, as we will go on to see.

  Within us sits a timekeeper, an internal clock that coordinates our neurological and bodily functions with the external world. As we approach the dead of night, this clock exerts its strongest influence, compelling us to sleep, and in the daytime makes us feel more alert.

  For the most part, these two mechanisms, the circadian and homeostatic, work in sync to ensure we sleep an appropriate amount at night and feel wide awake during the day. At least, they do when they are both working properly.

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  What I describe in the subsequent pages are patients I have seen over the years in the Sleep Disorders Centre, Guy’s Hospital, and at London Bridge Hospital. I have been incredibly fortunate to know some of these people for many years and to have gained an insight into their conditions and their lives. For others, I have had opportunities to delve into their world more deeply, to meet them and their families in their homes, outside the constraints of the clinic, where time is less restricted and our discussions more leisurely. They have all consented and collaborated in the descriptions of their cases, ensuring accuracy and veracity. The only details changed are names where marked with an asterisk.

  These patients illustrate the fundamental importance of sleep to our lives. And, as neurologist Oliver Sacks so aptly put it: ‘In examining disease, we gain wisdom about anatomy and physiology and biology. In examining the person with disease, we gain wisdom about life.’

  1

  GREENWICH MEAN TIME

  If you have ever been on a long-haul flight crossing time zones, the feeling of jet lag will be all too familiar. You know something is amiss: you feel sluggish and detached from your environment; the bright sunshine of your destination is discordant with your yearning to be tucked up in bed. There is the nausea of needing to stay awake when every fibre in your body craves sleep, or the incongruity of being wide awake at 2 a.m. while the world around you slumbers, and all you can think about is breakfast. Thankfully, your body soon adjusts, and within a few days you are back in tune with life around you. But imagine if that was how you felt all the time, that it was the reality of your daily life, and there was no hope of recovery.

  I first meet Vincent, and his mother Dahlia, at Guy’s Hospital. He is sixteen years old, and this particular clinic is specifically for teenagers transitioning from the sleep services in the children’s hospital to the adult world. Typically, this clinic is full of children with narcolepsy or severe sleepwalking. But Vincent is not typical in this regard – or, indeed, any other. He is a shy and reserved teenager, not particularly tall but stocky and well-built. I learn that this is testament to his enthusiasm for boxing. Dahlia, in contrast, is bubbly and very talkative. Originally from South America, she speaks English fluently but with a strong accent and at a machine-gun pace. For the most part, Vincent sits there quietly as Dahlia tells me the story of the past few years, only interrupting when his frustration bubbles over. When he does talk, he is slow and hesitant; he occasionally finds it difficult to find his words.

  Between them, they paint a picture of Vincent’s life.

  Vincent first became aware of some difficulties with sleep at around the age of nine or ten, but it was really only at the age of thirteen that his problems became much more evident. Dahlia thinks it started after Vincent had two operations on his hip, the second to remove metal plates inserted during the first procedure.

/>   ‘Well, it was kind of gradual. At first I didn’t really know what was happening,’ Vincent tells me. He was initially finding it harder and harder to fall asleep, drifting off at three or four in the morning. ‘The first time I properly realised it was a problem was when I was always trying to go to sleep, and then I started seeing the sun rise every time.’

  It quickly got to the point where Vincent would be wanting to fall asleep at eleven in the morning and wake up at nine in the evening. Unsurprisingly, his schooling quickly began to suffer. ‘I really missed a lot of school. At first I didn’t want to tell anybody that I was having trouble sleeping, because they would just think that I’m lazy. So I just told them I was unwell a lot.’

  For Dahlia, this time in their lives still stings. ‘I started to notice when I was trying to wake him up to go to school that I could not wake him for love nor money. I would shake him, but just not be able to get him up. I was so confused because he had never been late for primary school. Never! I thought I was being judged as a mother. Possibly Vincent thought he was being judged as a student too. I got into so much trouble with his school. I was fined for Vincent’s poor attendance!’

  Vincent also recalls feeling judged: ‘The school, my dad and friends found it hard to understand.’ Some people, including his father, from whom Dahlia is separated, raised the likelihood that it was simply a case of a typical teenager oversleeping, or that it was psychosomatic. In fact, I think Vincent’s father still considers this to be the case. On one occasion, I spoke to Dahlia on the telephone and I could hear him in the background, arguing with her that there was no medical issue.

  Dahlia knew that there was more to it than teenage sleep patterns, however, and as Vincent’s school attendance dropped further, she sought medical advice. Dahlia recalls taking Vincent to see their family doctor. ‘We went maybe about seven or eight times, a few months apart, just to say Vincent has a problem with sleep. [We got] the usual recommendations – give him a hot milky drink before bedtime, no screens at night – all of that. Lavender oil . . .’ she scoffs.

  The problem nevertheless persisted, and eventually Vincent was referred to a paediatrician. It was at this point, some two years after he had realised he had a problem, that Vincent finally received a diagnosis: Vincent’s internal body clock seemed to be set at the wrong time. Rather than being attuned to the world around him, he was told by doctors that his own body clock was running several hours later than everyone else’s. He was diagnosed with delayed sleep phase syndrome.

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  We are all children of the sun. We are enthralled by it, and enslaved by it; we march to the beat of the sun’s drum. Our sleep patterns are defined by the 24-hour rhythm of the rotation of the earth and our exposure to the sun’s light. This makes total sense: to be awake and foraging for food when it is light and we can see prey and predators, and to sleep when it is dark and we are vulnerable to predation, seems crucial to our survival. It is not only our sleep that is defined by this rhythm, however.

  Type ‘circadian rhythm’ – from the Latin for ‘about a day’ and the name for this 24-hour cycle – into PubMed, the most widely used search engine in the life sciences and medicine, and it will return over 70,000 hits – papers with titles ranging from ‘Biological clocks and rhythms of anger and aggression’ and ‘Circadian regulation of kidney function’ to ‘Biological clocks: their relevance to immune-allergic disease’. Our 24-hour rhythm influences our brain, our gut, our kidneys, our liver and our hormones – every cell in our bodies. In fact, remove a cell, place it in a Petri dish, and it will demonstrate a 24-hour rhythm in some form or other. Indeed, 40 per cent of our genes that encode proteins are under the regulation of this circadian rhythm.

  It is not simply a matter of exposure to light, though. The sun is not the metronome that keeps this rhythm going – at least not any more. Put humans in dim light, without any exposure to the rising and setting of the sun, and the rhythm will continue.

  In the 1930s, Nathaniel Kleitman, one of the founding fathers of modern sleep science, experimented on himself and others in the depths of Mammoth Cave, Kentucky, the longest known cave system in the world. Deep underground, without light and without fluctuations in temperature and humidity, he tried to impose a 28-hour cycle, but found he could not. Even in the absence of the external cue of the sun’s light, body temperature, sleep and other physiological parameters retain this 24-hour rhythm, implying that somewhere within us is a clock that keeps time.

  It also seems that this clock is common to all life on this planet. Bacteria, single-cell organisms, plants, flies, fish and whales – they all have this endogenous clock. For some lifeforms, the need for this clock is clear. But why should bacteria need to know what time it is, or indeed plants? Plants certainly need to know when the sun is shining, to know when to open their leaves and photosynthesise, but this does not need to be guided by an internal clock; simply detecting light would be enough. And why should fish living in cave systems, blind and not exposed to the light of the sun for thousands of generations, hold on to this clock? The fact that they do implies that this circadian rhythm is hardwired into the very essence of life, that since the existence of the last ‘universal common ancestor’, the very origin of all lifeforms on the planet, there has been an evolutionary pressure and natural selection acting to maintain this endogenous clock.

  At the most simple end of life as we know it, bacteria and algae, it is difficult to know what this pressure might have been, however. It has been proposed that the origins may lie in a desire to avoid cell replication, which involves the copying of genes, during times of exposure to ultraviolet radiation, known to produce mutations. A more widely accepted hypothesis is that these rhythms evolved to control the production of genes that pre-empt and counteract daily fluctuations in oxygen levels and the damage that oxygen does. The circadian rhythm may in fact date back to the Great Oxygenation Event, approximately 2.45 billion years ago. This time period is defined by the evolution of bacteria called cyanobacteria, believed to have been the first microbes to achieve photosynthesis – the conversion of carbon dioxide to oxygen using energy from the sun’s rays. At that time, atmospheric oxygen levels were low, and any free oxygen quickly became chemically bound to other substances. But the sudden rise in free atmospheric oxygen caused by cyanobacteria is thought to have provoked one of the largest mass extinctions in the history of the world, killing off most organisms for whom oxygen was highly toxic. Surviving organisms needed to develop mechanisms to protect themselves from the dangerous effects of free oxygen. It is thought that this need for protection resulted in the evolution of proteins called redox proteins, which mop up the toxic by-products of chemical reactions involving oxygen. The theory suggests that by predicting sunlight, and knowing when oxygen levels are going to rise, organisms can protect themselves from toxic damage, by generating these proteins at an appropriate time of day. But the truth is the origins of the circadian rhythm remain a mystery.

  Any clock needs to be adjustable or reset, like a horologist tinkering with the pendulum of a grandfather clock to keep it running on time. The circadian rhythm, particularly for more complex organisms, needs to be tweaked according to the changing patterns of our seasons. Over the past few decades, our understanding of how this occurs has advanced. We are now aware of the influence of environmental cues or influences that gently nudge our circadian rhythms forward or back. These are termed Zeitgebers – ‘givers of time’ in German. Left to its own devices, the human circadian rhythm is set to 24.2 hours, and without Zeitgebers we would eventually find our internal clock drifting relative to the world around us. Our internal clock is sensitive to temperature, physical activity and eating, but by far the most potent Zeitgeber is light – particularly light at the blue end of the spectrum, like sunlight. While our circadian clock has proved itself independent of the sun, therefore, it is still its greatest influence.

  The Royal Observatory, Greenwich, only a few minutes’ train ride from t
he Sleep Disorders Centre, Guy’s Hospital, sits atop a hill overlooking a large loop in the River Thames. From the thirtieth floor of the hospital, I can see the hill rising slowly towards south-east London, but cannot quite make out the building between the forest of ugly 1960s towers and new skyscrapers. On the roof of the observatory, a large metal mast with a weather vane on its tip juts into the typically grey London sky. On this mast, a large red ball, several feet in diameter, is impaled. Every day, at 12.55 p.m. Greenwich Mean Time in the winter, British Summer Time in the summer, the ball rises halfway up; then, at 12.58 p.m., ascends to the top. At 1 p.m. exactly, the time ball drops down the mast. In the present day, the area around the observatory is dominated by the skyscrapers of Canary Wharf, the main financial district of London, looming over the city from across the river. In the mid-nineteenth century, however, the Thames below would have been chock-full of sailing ships, ferrying the lifeblood of trade through the British Empire. Hundreds of telescopes would have been focused on the time ball of the observatory, waiting for the ball to drop. This would be the sailors’ opportunity to reset the chronometer on board each ship to Greenwich Mean Time, crucial for the calculation of longitude on their journeys to the East Indies and beyond.

  Like the chronometers on these ships, there are multiple clocks within the human body, but the seat of the master clock – the large red ball of the Royal Observatory – in humans, and indeed all vertebrates, is a tiny area of the brain called the suprachiasmatic nucleus. This tiny area, comprising a paltry few thousand neurones, sits in the hypothalamus, immediately above the optic chiasm, where the optic nerves carrying information from the eyes merge. This tiny nub of tissue is the control room for all circadian rhythms throughout the body, and destruction of the suprachiasmatic nucleus results in the loss of this rhythmicity.