The Spark of Life: Electricity in the Human Body (33 page)

Epilepsy has been known since antiquity. Hippocrates referred to it as the ‘sacred disease’, and correctly argued that it was caused by a disturbance of brain function. Nevertheless, for many centuries the view that epilepsy was a medical problem coexisted with the idea that epileptic individuals had been cursed by the gods or were possessed by evil spirits. Epileptics were often ostracized and by the sixteenth century were even branded as witches. Gradually, it was recognized that epilepsy was an illness, but it still carried a negative aura. When Prince John, the youngest son of King George V, developed epilepsy he was hidden away in a cottage on the Sandringham estate. Fortunately, these days there is no stigma attached to the disease.

The origins of epilepsy are still not fully understood. In some cases it results from a traumatic brain injury, a tumour that presses on the brain, or brain damage sustained during birth. In other cases it is inherited and caused by mutations in specific genes, many of which are ion channels. Most of these mutations impair the electrical activity of inhibitory nerve cells that normally exert a brake on brain activity. Release the brake and the brain goes into overdrive as excitatory circuits then become over-stimulated.

Early treatments for epilepsy were bizarre, ranging from Pliny’s advice to drink the blood of gladiators to Robert Boyle’s suggestion to eat crushed mistletoe, ‘as much as can be held on a sixpence coin’, when the moon was full. A landmark in therapy came when it was recognized in the late nineteenth century that removal of the trigger area could help treat epilepsy. Surgery is not always possible, however, and other parts of the brain may be damaged when removing epileptic foci. Current therapies often involve drugs that reduce the frequency and intensity of seizures. Many act by enhancing the release or action of the inhibitory transmitter GABA, which prevents excess electrical activity by holding nerve cells at a more negative level. Others suppress the activity of excitatory neurones directly by acting on the sodium and potassium channels involved. However, as epileptic seizures can damage the brain, such therapies may only have partial success unless the patient can be treated early.

Some unfortunate children have intractable epilepsy that is unresponsive to drug therapy and involves parts of the brain inaccessible to surgery. An old treatment that is surprisingly effective in some of these patients is to severely restrict their consumption of carbohydrates. Known as the ketogenic diet because it leads to the rise of metabolic by-products known as ketone bodies in the blood, it stops most seizures in about a third of patients and reduces their frequency in a further third. Why it works is far from clear, but the patients and their parents are not bothered about that. It is not an easy diet to stick to, however, and consumption of a single chocolate bar or other carbohydrate treat can precipitate a seizure.

Wiring the Brain

As this chapter has shown, the way the brain is wired up determines the intricate pattern of electrical impulses and ‘chemical kisses’ between cells, and so influences how we move our limbs and sense our environment. But it has a still more important and extraordinary function. As we shall see next, it determines our emotions, thoughts, personality, consciousness – our very sense of self.

11

Mind Matters

        O body swayed to music, o brightening glance,

        How can we know the dancer from the dance?

W. B .Yeats, ‘Among Schoolchildren’

Joy, sadness, fear, anger, exhilaration, despair; our emotions fluctuate like sunshine and clouds in a British summer. They influence our thoughts, dictate our actions and form the basis of our personalities. But we are not mere puppets of our emotions. We are also capable of reasoned argument, of rational thought and action, of creative ideas that seem to come from out of the blue. Contrary to the mediaeval view, there is not some homunculus sitting in our brain pulling the strings. Rather, blind evolutionary forces have shaped our brains so that everything we think, feel and do is governed by the electrical and chemical events taking place in our nerve cells. It may seem uncomfortable to consider that your thoughts and feelings are determined simply by clouds of chemicals washing through your brain, and by the changing patterns of electrical activity they produce. Yet with a moment’s thought you will recognize that this is indeed the case, for drugs, hormones and diseases that alter the levels of neurotransmitters in our brain affect us deeply, transforming our emotions and our behaviour.

A small amount of alcohol, for example, may usher in a more outgoing personality, cause us to behave irrationally, or sink into melancholy. Women’s moods may fluctuate with their menstrual cycle. Regular running can produce a high so pleasurable that aficionados become stressed and irritable if they are prevented from exercising. Adenosine, administered to control the heart rate, has the extraordinary side-effect of producing a transitory feeling of impending doom so severe that the patient may feel they are about to die. Parkinson’s disease is noteworthy for its high incidence of associated depression. Syphilis causes marked changes in temperament, most famously in King Henry VIII. Simply stimulating certain regions of the brain can produce euphoria, anger – even, it has been claimed, spiritual experiences. All human emotions have their origins in the electrochemistry of the brain, and an intricate tapestry of chemical and electrical signals governs our every thought and action.

This penultimate chapter considers how neurotransmitters influence our moods, our memories and our thoughts, and how drugs of abuse enhance or mimic their effects. It looks at how our personalities are shaped by the electrical activity of our brain and considers what happens to us during sleep and anaesthesia. And it addresses the question that has perplexed mankind for centuries – what is consciousness and who, exactly, am I?

What a Pleasure

We are pre-programmed to seek pleasure. Food, sex, drink, exercise – all produce feelings of enjoyment that drive us to seek more. But our impulse to do so is more than hedonism or sheer sensual delight; it is a way of ensuring that our species survives. All pleasurable experiences stimulate the reward centre of the brain. This consists of several distinct brain regions, including the nucleus accumbens, the amygdala and the ventral tegmental area, which are wired together by a group of nerve cells known as the median forebrain bundle. Dopamine, one of the most crucial neurotransmitters in the brain, is intimately involved in desire and addiction. Pleasurable experiences such as sex, love and food trigger the release of dopamine in the brain’s reward centre, which increases nerve cell electrical activity, reinforcing our sensation of pleasure and coercing us to have yet another chocolate or glass of wine – too much in some cases. Many drugs of addiction act by increasing the concentration of dopamine in the nucleus accumbens, thereby producing feelings of euphoria.

Long ago when I was just a teenager I went to see a film at the local cinema with a school friend and her family. The queue was enormous and it was clear that we were unlikely to get in. ‘Never mind’, said my friend’s mother, ‘let’s go home and try the cocaine.’ This was not as outrageous a suggestion as you might imagine. Her son had just returned from South America with a bag of coca leaves. These have been chewed by Peruvian Indians for over 8,000 years, mainly because alkaloids in the leaves act as an appetite suppressant and help keep them awake. I, however, did not find it a stimulating experience – all that happened was that my lips and tongue were slowly and mildly anaesthetized, rather as if I had been to the dentist. Nothing else. Perhaps this may have been because I was far too nervous to take more than the tiniest bite of a leaf or two: even then, cocaine, which originates from coca leaves, had a fearsome reputation as a drug of abuse.

Initially, however, it was widely lauded. Sigmund Freud regularly took cocaine while writing
The Interpretation of Dreams
, as he found that cocaine caused ‘exhilaration and lasting euphoria’ and had such a ‘wonderful stimulating effect’ that ‘long-lasting intensive mental or physical work can be performed without fatigue’. In the nineteenth century a cocaine-laced drink, Vin Mariani, hailed as a tonic for body and brain, was such a favourite of Pope Leo XIII that he awarded it a special gold medal and appeared on a poster extolling its virtues. A pinch of coca leaves was also added to the original brew of Coca-Cola, along with extracts of the kola plant (hence its name). The power of cocaine to banish tiredness was even exploited by explorers. Both Ernest Shackleton and Captain Robert Scott took ‘Forced March’ cocaine tablets with them to Antarctica and during World War I it was supplied to some British troops to enhance their endurance.

Cocaine acts by preventing clearance of the neurotransmitter dopamine, released in response to nerve impulses, from the synaptic cleft. Consequently, dopamine hangs around longer and continues to stimulate its target cells. Amphetamine (speed) acts in a similar way. The addictive properties of both drugs come from the fact that dopamine stimulates the reward centre of the brain, so that pure cocaine produces feelings of exhilaration and euphoria, as Freud described. Providing that the body continues to be supplied with cocaine, dopamine levels in the brain remain elevated and the pleasurable sensation continues. When the drug wears off, however, the dopamine concentration plummets to below normal levels, producing depression, anxiety and a craving for more drug. Addiction, then, is an affliction of the brain and anything that stimulates the brain’s reward centres to excess has the potential to be addictive.

Hooked

Nicotine is one of the most addictive drugs known. It is found in the leaves of the tobacco plant,
Nicotiana tabaccum
, which is named after the sixteenth-century adventurer Jean Nicot who brought the plant to France and is said to have popularized its use as a treatment for headache. Tobacco was introduced into England by Sir John Hawkins in 1565 and at first was met with amazement and considerable opposition. There is a famous story, probably apocryphal, that Sir Walter Raleigh’s servant emptied a bucket of water over him in the mistaken belief that his master was on fire. Kings and papal bulls banned its use. King James I of England wrote a famous
Counterblaste to Tobacco
in 1604, calling it ‘a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs and in the black stinking fume thereof, nearest resembling the horrible Stygian smoke of the pit that is bottomless’. Gradually, however, tobacco use proliferated, becoming widespread by the middle of the last century.

Smoking is an expensive habit in every sense. Every hour, twelve people in the UK die from smoking-related diseases and many more in the United States, and billions of dollars are spent on smoking-related health costs – over 190 billion dollars per year in the USA alone. It is estimated that half of cigarette smokers will eventually be killed by their habit, for smoking dramatically increases the risk of lung cancer (85 per cent of lung cancer cases are due to smoking) and is also associated with heart disease, stroke, emphysema and a range of other cancers. The link between smoking and lung cancer was established by Sir Richard Doll in the early 1950s, but the idea initially met with considerable resistance. Concerted health campaigns over the past fifty years have led to a decline in tobacco use and a corresponding fall in lung cancer rates, but around 20 per cent of adults still smoke. As everyone knows, it is not the nicotine in cigarettes that causes cancer but a cocktail of carcinogens contained in tobacco smoke; nicotine is dangerous because it is highly addictive and its tenacious hold makes it difficult to quit smoking.

Nicotine acts on acetylcholine receptors found at the junctions between nerve and skeletal muscle and at certain nerve–nerve synapses in the brain. Like acetylcholine itself, binding of nicotine to acetylcholine receptors opens an ion channel that allows sodium ions to enter the nerve cell and so stimulates it to fire off an electrical impulse. It is the drug’s ability to activate certain brain neurones that accounts for its actions as a stimulant and, like caffeine, enables you to concentrate more effectively when tired. Its addictive properties stem from the fact that it also stimulates nerve cells in the reward pathways in the brain. Regular smokers adjust their smoking to maintain a constant concentration of nicotine in their blood and brain, and thus a steady level of neuronal stimulation. Some individuals have genetic differences in the liver enzyme that breaks down nicotine, so that the drug remains in their bloodstream for longer and they smoke fewer cigarettes to obtain the same effect.

Love, Love Me Do

‘Tell me where is fancy bred, Or in the heart, or in the head?’, asks Shakespeare in
The Merchant of Venice
. Romantic love has long been a favourite topic for authors, artists and playwrights, but what does cause us to fall in love? To seek the perfect mate and stick with them forever – or to favour the fresher faces, being constant only to inconstancy? The lovesick have often wished for a simple means to make the object of their affection fall in love with them. This is the basis of many charms and potions, perhaps even our predilection for cosmetics, perfume and dressing up. In
A Midsummer Night’s Dream
, a love potion made from the juice of heartsease (the wild pansy) famously creates mayhem. It is administered to an unsuspecting Titania while she sleeps and compels her to fall in love with the first living thing she sees on waking. It happens to be Bottom, a most unprepossessing object of desire, since his head has been transformed into that of an ass. Yet although we may scoff at the idea of magical love potions, recent research suggests love is indeed no more than a chemical phenomenon.

Our understanding of the chemistry of attraction has its origin in a somewhat unlikely source – a rather unappealing small rodent known as the prairie vole. Prairie voles are monogamous and bond for life. In contrast, their cousins the montane voles are highly promiscuous, preferring to confine themselves to one-night stands. The difference in their behaviour seems to be related to two specific brain chemicals, oxytocin and vasopressin, that are released during mating. Oxytocin is crucial for pair bonding because its injection into the nucleus accumbens is sufficient to cement a couple for life, even if they are prevented from having sex. Conversely, if oxytocin action is blocked the prairie vole is only interested in fleeting affairs. Injecting oxytocin into a montane vole, however, does not dissuade it from a life of promiscuity, because it lacks oxytocin receptors in the reward centres of its brain. Oxytocin induces the release of dopamine and both are thought to act in concert to make pair bonding a particularly pleasurable experience. Vasopressin is similarly important for pair bonding, especially in males, and also provokes the aggressive behaviour that male voles display towards potential rivals during courtship and when defending the nest. It has also been linked to aggression in humans.

Clearly, it would be injudicious to extrapolate directly from voles to humans, for both the human brain and our social interactions are far more complex and involve multiple transmitters and many brain regions. Nevertheless, oxytocin is also important for bonding in humans. It is released during sex and suckling and may help cement the links between lovers, and between mother and child. It also enhances trust between people, an essential component of any loving relationship. Dopamine, that arbiter of pleasure and addiction, also plays an important role in romantic love. When the brain activity of students who claimed to be madly in love was examined in a scanner, dopamine-rich regions lit up when they were shown an image of their beloved. Thus here, to answer Shakespeare’s question, is where fancy is bred, and in a very real sense, we may be addicted to the object of our love.

The (Un)Happiness Hormone

If pleasure is a construct of the brain, so too is misery. ‘A mark in every face I meet, Marks of weakness, marks of woe’ – as William Blake wrote, unhappiness is everywhere. So too is her more severe sister, clinical depression, for it is estimated that at some stage of our life almost 10 per cent of us will suffer from the ‘black dog’, as Winston Churchill termed it. In some people, it can be so severe that it is totally incapacitating.

Happiness and despair are the two faces of the neurotransmitter serotonin. Serotonin is produced by neurones of the raphe nucleus, whose processes ramify throughout the brain. Their targets include the nucleus accumbens and the ventral tegmental area, part of the brain’s reward system. Because serotonin is released in many brain regions and interacts with at least fourteen different kinds of receptor, it affects many types of behaviour, but one of its most important roles is mood control. Elevated levels of serotonin are associated with feelings of optimism, contentment and serenity. Too little brings despair, depression, anxiety, apathy, and feelings of inadequacy. One way of increasing your serotonin levels is by vigorous exercise, which is why a brisk walk or a game of squash (if you can drag yourself off the sofa) helps relieve the blues. Modern antidepressants such as Prozac also act by elevating serotonin concentrations. They do so by inhibiting the removal of serotonin from the synaptic cleft, so that the transmitter stimulates its receptors for longer.