The Little Grey Cells
Your brain is one of the most sophisticated machines on the planet. It has over 100 billion nerve cells and each of them communicates with many thousands of others. There are trillions of connections, as many as in the whole of the world’s telephone system and far too many to fully comprehend. But the brain is not simply a great mass of interconnected nerve cells. It is a highly organized structure, with different parts being specialized for different purposes.
The most important bit of the brain – that responsible for our thoughts and actions – is the forebrain or cerebrum. It makes up about 80 per cent of the weight of the human brain and is divided into two mirror-image cerebral hemispheres, each of which primarily interacts with one side of the body. For unknown reasons, the wiring is crossed, with nerves from the left side of the body going to the right side of the brain and vice versa. The cerebral hemispheres are wired together by the corpus callosum, the brain’s information superhighway: cut it, and you cannot name what lies in the left half of your visual field because the image is presented to the right side of your brain whereas language is processed on the left side of your brain.
The outer layer of the forebrain, known as the cerebral cortex, is made up of a thin sheet of nerve cells that is thrown into numerous folds to increase its surface area and enable more to be packed into the skull. Its highly convoluted structure makes it look rather like a walnut kernel. It is this four-millimetre thick layer of cells that mediates thinking, conscious actions, sensation, learning and memory, and different parts of it are specialized for different functions. Below the outer shell of nerve cells the forebrain is packed with nerve fibres that run to and fro wiring the nerve cells of the cortex together. So vast in number are these interconnections that the cortex spends most of its time talking to itself.
Cross-section of the human brain showing the major regions.
Below the forebrain lie regions of the brain that are involved in controlling the emotions, in regulating appetite and sleep, and that act as relay centres for processing information coming in from the sense organs and handing it on to the cerebral cortex. Even further down, at the base of the brain, sits the brainstem, which connects the upper parts of the brain to the spinal cord. It controls all your unconscious actions: here is where breathing, blood pressure, heart rate, digestion and so on are regulated. These regions may continue to survive and function even when higher brain functions have ceased, a condition known as a persistent vegetative state, in which the patient is often referred to as a vegetable. This bit of the brain is similar in structure to that found in many other creatures, and serves the same role: indeed, it is sometimes known as the reptilian brain.
Curled up at the back of the brain at the top of the brainstem is the cerebellum (or ‘little brain’), which helps control balance and coordinates movements. It is involved in learning skilled motor tasks such as riding a bicycle, driving a car, and dancing Les Sylphides; damage it, and you cannot walk properly, but stagger around as if drunk.
Agatha Christie’s famous detective Hercule Poirot was very proud of his ‘little grey cells’. He was referring to the fact that although the living brain is a pinky-brown colour, when it is pickled the nerve cells turn grey, and hence are known as the grey matter. Nerve fibres, on the other hand, appear white and shiny when pickled (because of their myelin coats) and are called the white matter. But the brain does not consist solely of nerve cells. There are almost as many supporting cells, called glia, which help guide developing nerve cells on their way, supply them with nutrients, envelop them within a myelin sheath and guard them against infection. The delicate brain tissues are enveloped by membranes (the meninges) and shielded by a protective skull; within it, the brain floats in a sea of cerebrospinal fluid that cushions it and prevents it being damaged if the head is accidentally knocked, in the same way that the amniotic fluid protects the developing baby in the womb.
The brain has a large blood supply and many people will die, and an even larger number will be permanently handicapped, by blockage or rupture of the cerebral blood vessels, such as occurs in a stroke. Loss of the blood supply in this way leads to death of nerve cells in the local environment through lack of oxygen and nutrients and the build-up of toxic waste products. However, brain cells are not in direct contact with the bloodstream, but are protected by the blood-brain barrier. This is formed from the layer of cells that line the smallest blood vessels, which are so tightly knit together that they prevent substances leaking between the bloodstream and the cerebrospinal fluid. This blood–brain barrier is an important defence against noxious substances and infectious agents, such as bacteria and viruses, which drift around in the bloodstream.
The brainstem is directly connected to the spinal cord. When you decide to wriggle your fingers and toes the brain sends signals down the spinal cord and out along the peripheral nerves to command your muscles to move. The nerves that come out of the spinal cord in the small of the back and below serve the muscles of the legs; those higher up in the neck region signal to the arms. Damage to the nerves in the spinal cord means that electrical signals will be disrupted leading to paralysis and loss of sensation, as everything below the injury ceases to function properly. People who sever their spinal cord in the middle of their back can no longer walk but will still be able to breathe and move their arms. Break your neck, however, and you may be unable to move or feel anything in your arms as well. Depending on the exact location of the break, you may also be unable to breathe unaided.
Damaged nerve fibres in the brain and spinal cord never recover, leaving the patient permanently disabled. This was known even to the Ancient Egyptians, who declared that a person having ‘a dislocation in a vertebra of his neck’ is unaware of his legs and arms and cannot be treated. Over 3,700 years later, it is still the case. Not so for the peripheral nerves. My father severed the nerves in his fingers when adjusting the blade on an old lawn-mower and was left with no sensation in his fingertips, a devastating blow for a potter. Within a year or so, however, he was able to feel his fingertips once again as the nerves had grown back: but the regrowth was a slow process, inching forwards at less than two millimetres a day.
Seeing Single Cells
Individual brain cells are so tiny that it was not possible to see them until the invention of the microscope. Even then, the huge interconnected mass of cells within the brain and nerve trunks meant that special stains were needed to visualize individual cells clearly. In 1871, Camillo Golgi developed just such a stain.
While working as a medical officer in a psychiatric hospital in northern Italy, Golgi pursued his real passion – unravelling the anatomy of the brain – in a makeshift laboratory converted from an old kitchen. After a long series of attempts he discovered that a combination of potassium dichromate and silver nitrate stained a very few nerve cells randomly, but in their entirety. Paradoxically, the most important thing about Golgi’s method was that it hardly ever worked, for the fact that only a few cells were stained meant that for the first time it was possible to see the spidery shape of a single nerve cell in all its glory, with its multiple, delicate dendrites and long, thread-like axon.
The great Spanish anatomist Santiago Ramón y Cajal subsequently made a series of stunningly beautiful drawings of nerve cells visualized using Golgi’s silver-staining method. He was a gifted draughtsman and had originally wished to be an artist, but his father persuaded him to study medicine. In the event he combined both professions. Based on his observations, Cajal proposed that each nerve cell is a distinct entity and physically separate from its neighbour. This led to a dispute with Golgi, who had a different idea. In the end, however, Cajal turned out to be right.
While silver staining enables a small number of neurones to be visualized in exquisite detail, it is not possible to see how neurones are connected together. What is needed is some way of colour-coding adjacent cells with different stains. This was achieved in 2007, using genetic techniques to label neuron
es with multiple different colours. In the same way that a television uses only three colours to produce many different hues, three different genetically encoded fluorescent dyes were used to paint the brain of a mouse. In one region of the ‘brainbow’ mouse brain over ninety different colours were distinguished, enabling the connections between neurones to be traced. It was not just clever science – it was also a work of art.
Drawing of Purkinje nerve cells (A) and granule nerve cell (B) from a pigeon brain by Santiago Ramón y Cajal, 1899. The cells were stained with the silver stain developed by Camillo Golgi. The small ‘knots’ on the dendrites are dendritic spines.
Taking the Brain Apart
Understanding how the brain is wired up, how information flows from one region to another, and how information is coded and processed is one of the most challenging and complex tasks in neuroscience. In an electronic circuit, such as that of a radio, the wiring diagram details the connections between individual components and how information flows around the circuit. There is only one animal on the planet for which the complete wiring diagram of the nervous system is known and that is a microscopic nematode worm called Caenorhabditis elegans that lives in the soil. It is a scientific supermodel and has received even more attention than the catwalk variety. Because it is so small and has such a simple nervous system, every single nerve cell and every connection is known. It has 302 neurones, about 5,000 chemical synapses, 600 electrical synapses and 2,000 nerve–muscle connections.
The enormous complexity of the human brain and the difficulty of identifying individual connections make construction of a similar circuit diagram for our own brains an almost insurmountable problem, never mind the fact that it would be different in each individual and would change as we learn new skills and have new experiences. Nevertheless, we are not entirely ignorant of how our brains work.
The idea that different bits of the brain are specialized for specific functions was first championed by Franz Joseph Gall in the early nineteenth century. By extensively examining the skulls of his friends, his patients and the inmates of local asylums and prisons, he came to the conclusion that different bits of the brain were associated with different mental attributes such as valour, cautiousness, ambition, wit and mechanical skill, and that this was reflected in the size and shape of the overlying skull. A charismatic speaker, he travelled throughout Europe delivering public lectures on his ideas, even giving a presentation to the German royal family. He also amassed a collection of 300 human skulls and over 100 plaster casts. But although phrenology – the practice of deducing a person’s character from the bumps on their head – enjoyed a brief vogue, it has no basis in science.
The first real clues to understanding what jobs different brain regions carry out came from studying people with brain damage caused by injury or disease. One of the most celebrated of these individuals was Phineas Gage. On 13 September 1848, Gage was the foreman of a gang of construction workers building the bed of a new railway line outside the town of Cavendish in Vermont. He was preparing to explode a large boulder and was using a long iron rod (one and a quarter inches in diameter, about four feet long and more than thirteen pounds in weight) to tamp down the blasting powder into a hole drilled in the rock. Alas, a spark caused by the iron striking the rock ignited the dynamite, which exploded, driving the rod straight through Gage’s skull. It entered through the left cheekbone, damaging his eye, and exited though the top of his head, landing some twenty-five metres away, smeared with his blood and brains. Gage ‘was thrown upon his back, and gave a few convulsive motions of the extremities’ but rather remarkably he spoke within a few minutes, was able to sit upright in the cart that transported him to his hotel and then even walked up a long flight of stairs. The first doctor to examine him was disinclined to believe his story until Gage got up and vomited and ‘the effort of vomiting pressed out about half a teacupful of the brain, which fell upon the floor’. A second physician, who arrived an hour and a half later, found Gage conscious and talking, but noted that both ‘he and his bed were covered in gore’.
Although Gage recovered physically, it soon became clear the accident had changed him. Previously of well-balanced mind, friendly, energetic, hard-working, and a great favourite with his colleagues, he became obstinate, vacillating, uncooperative and indulged in ‘the greatest profanity’. He was, said his friends, no longer the same man. What Gage’s story shows is that our personality and emotions are linked to the function of certain brain regions. The damage to his prefrontal cortex had led to his inappropriate behaviour and loss of social inhibitions.
Another unfortunate whose ailment provided information about where different functions are located in the brain was Monsieur Leborgne, who was unable to say anything other than ‘tan’ when Paul Broca examined him in 1861. When Leborgne died shortly afterwards, a post-mortem revealed that a small region of his left cerebral hemisphere was damaged. Immortalized as Broca’s area, this region of the brain is concerned with speech production. A few years later, Carl Wernicke discovered several patients with a different speech problem: although able to articulate words clearly and fluently, they simply spoke gibberish, a meaningless, incoherent rush of disconnected words, but with the syntax of the sentences more or less correct, such as in, ‘I can’t talk all of the things I do, and part of the part I can go alright, but I can’t tell from the other people.’ It is now recognized that this bit of the brain is involved in language comprehension. Wernicke’s area lies some distance from Broca’s area further towards the back of the brain.
For most purposes, the left and right sides of our brains are symmetrical. Language, however, is confined largely to the left side of the brain. A patient who has a stroke in their left cerebral hemisphere may therefore find themselves paralysed down the right side of their body and unable to speak. By contrast, a stroke on the right side of the brain can lead to paralysis of the left side of the body but usually has only a limited effect on speech. Fascinatingly, people whose Broca’s area has been damaged by a stroke are often able to sing words that they cannot speak – it seems that singing involves an entirely different bit of the brain.
All Fired Up and Ready to Go
Another means of determining what function a specific brain region performs is to stimulate it directly with a small electric current. One of the first scientists to do so in a systematic fashion was Eduard Hitzig, who in the mid-1800s experimented on Prussian soldiers whose skulls had been shattered by bullets, leaving part of their brain exposed. Hitzig noticed that when a small current was applied directly to the brain it caused involuntary muscle contractions in the subject. Subsequent studies on dogs revealed that a small strip of cerebral cortex – now known as the motor cortex – controlled the movement of specific parts of the body.
In a similar fashion, sounds, sights and even the sense of touch are mapped onto the cerebral cortex. At the top of the brain sits the somatosensory system. Here, inputs from sense organs in your skin are neatly arranged so that all the signals from one location on your skin go to the same bit of the brain: legs, feet, fingers and toes each get their own areas. The most sensitive parts of the body, like the lips, fingers and genitals, are assigned larger brain areas, with more neurones, than less sensitive parts of your skin like the small of the back. Similarly, inputs from your eyes are mapped onto the visual cortex at the back of the brain, with the signals received by the same part of your visual field going to the same place, while sounds are organized according to frequency in the auditory cortex. Indeed, it now seems that there may be several such maps for each of the senses: like all good machines, the brain may have some built-in redundancy. The information is not wired straight through, however: it passes through many relay stations and is highly processed en route.
The ability to evoke sensation and action simply by stimulating a specific region of the brain is of considerable clinical significance. It is often used in brain operations to ensure, for example, that a surgeon removing a tumour removes the c
orrect bit and nothing else. During this operation the patient is awake and able to say what they feel: it does not hurt as the brain has no pain receptors and local anaesthetics are used to dull the pain fibres in the skin overlying the skull. Such operations can also yield useful information about where memories, words and information are stored.
Brain Waves
Early studies of the brain thus operated on much the same principle as a small boy with a new mechanical toy, who takes it to pieces to see how it works. More recently, non-invasive ways of looking at brain function have been devised, in which it is possible simply to watch what happens by recording brain activity.
The first of these techniques is the electroencephalogram (EEG), which is a record of your brain waves. Just as it is possible to record the electrical activity of your heart cells from electrodes attached to your chest, so it is possible to see what is going on inside your brain from multiple electrodes stuck to your scalp with conductive jelly. These pick up the minute voltage changes generated by the collective activity of millions of nerve cells in the surface layer of your brain. Your brain waves appear as oscillations in voltage that are constantly changing in frequency and amplitude as different regions of your brain surge into activity or fall silent. The EEG is much smaller and more difficult to record than the electrocardiogram and far more difficult to interpret. It’s a little like trying to understand the complex relationships between people living in a large city by listening in on all their telephone calls simultaneously: the multiple unconnected conversations make little sense and the vast number of them means it is impossible to pick out individual conversations.
The Spark of Life: Electricity in the Human Body Page 24
