We Are Our Brains (31 page)

More is gradually emerging about why some people are more prone to delirium than others. Delirium is basically caused by an overdose of the chemical messenger dopamine. There are a great many tiny variations, polymorphisms, in the DNA of the gene that produces the protein that receives the dopamine message in the brain cells. Those tiny variations are what make you more or less susceptible to delirium. Delirium causes brain damage and increases the risk of dementia. And its effects can last a long time. Many people experience long-term problems with reading, writing, walking, and memory and never recover entirely. Around a third of people over sixty-five who experience delirium die within a few months. So it's a serious disorder and one whose risk is determined from the moment of conception.

Hearing Voices

There are people who aren't psychotic and yet do hear voices. In fact, between 7 and 15 percent of the population hear voices, yet only a fraction have mental health problems. This phenomenon
forms part of a spectrum, with healthy people who hear voices at one end and schizophrenia patients at the other. People who hear voices at the onset or in the wake of a psychosis are somewhere in the middle. In healthy individuals, hearing voices frequently starts at a young age and tends to run in families. It often takes quite a while for children to discover that other people don't hear voices, after which they tend to be afraid to talk about such experiences. Some are very attached to their friendly voices, like the lady whose voices had told her since the age of eleven that there was no reason to be afraid. Patients with mental health problems, however, often hear voices with threatening, negative messages (“Why don't you jump in front of a train today?” or “You must die, Evelyn, you're evil, and evil people must die”). No wonder that voices like that produce paranoia and psychosis. By contrast, the voices that healthy people hear typically provide friendly help and advice, though there are cases of them saying nasty things like, “You're ugly, you're worthless, you're fat.”

Unlike psychotic patients, healthy people can control their voices. They can call them up as well as order them to go away at inconvenient times. Functional brain scans show that in the healthy group, brain activity isn't very different from that of patients with psychosis. In both cases, activity is seen in Broca's area (language production) and Wernicke's area (hearing, processing, and understanding language) (
fig. 8
) and the primary auditory cortex is activated (
fig. 22
). It looks as if the links between those areas are disrupted, which would tie in with the theory that when input to a particular brain area is reduced, that area starts to produce its own information (see earlier in this chapter). In people who hear nasty voices, the right side of the brain is much more active. Attempts have been made to silence the voices by means of transcranial magnetic stimulation of the overactive area, but up to now that method has proved no more effective than placebos. I wonder how many people who work as TV psychics or claim to have paranormal gifts aren't receiving messages from the other side but are just hearing their own brains.

Olfactory Hallucinations

The uncus (
fig. 21
) is a structure located in the front of the temporal lobe above the amygdala that is involved in smell. While conducting an orchestra, the famous composer George Gershwin suddenly started to smell burnt rubber and blacked out for ten to twenty seconds. He'd had an uncinate fit, which is an olfactory hallucination sometimes associated with epilepsy. Despite consulting a great many doctors, it took six months before Gershwin's fits—which grew increasingly frequent—were shown to be caused by a tumor of the uncus. Gershwin died in 1937 at the age of thirty-eight, shortly after the tumor was partially removed.

My father went blind in the last year of his life. He lived to be eighty-nine. Fifteen years ago we would go to Leiden together every week, where he was undergoing laser treatment for degeneration of his retina. The retina, which evolves during fetal development from a bulge in the brain, converts light into electrical signals that the optic nerve transports to the back of the brain, where we see. When I arrived at the teaching hospital in Leiden for the first
time with my practically blind father on my arm, I said, “We have to make a right here.” “How do you know that, have you been here before?” he asked. “No, but there's a great big sign with an eye on it and an arrow pointing to the right,” I explained. Without missing a beat, he said, “I'd love to know what their signs for gynecology and obstetrics look like.” He had the most common form of age-related blindness: macular degeneration. It's caused by new blood vessels growing right under the yellow spot (the macula), the part of the retina where you see the best. This destroys the retina, and you begin to lose your sight, starting in the middle of your field of vision. At first the objects you see are distorted, then a black spot forms in the middle of your central vision, which gradually becomes larger. In the wet form of macular degeneration, the new blood vessels leak blood and fluid. Reading and writing soon become impossible, and in the long run you can't even make out large objects. On the journey back to Amsterdam after my father's first laser treatment in Leiden, he asked me what month it was. “January,” I answered. “That's odd,” said my father, “surely it's much too early for the bulb season?” It turned out that the injection of fluorescent substance he had been given in preparation for the laser treatment made everything look yellow, creating the illusion that the tulip fields were in bloom. The laser therapy, alas, didn't help preserve what little remaining sight he had.

After my father's death, laser treatment improved, and an effective therapy has recently been devised for wet macular degeneration. Antibodies like Avastin have now been developed that inhibit the vascular endothelial growth factor (VEGF), the molecule that prompts the growth of new blood vessels that destroy the retina. In order to halt the degenerative process, this substance has to be injected into the eye every month using an extremely thin needle. A similar substance called Lucentis has since been devised specifically for optical use. It is said to stabilize the condition in over 90 percent of patients and even improve vision in a third of this group. Other forms of therapy for macular degeneration are under development as well. In a short
space of time, wet macular degeneration has gone from being an incurable to a treatable eye disease. The breakthrough in treating it came from Avastin, which was originally developed as a medication for intestinal cancer. That's often the way in medicine: However carefully you target your approach to a particular disease, the breakthrough often comes from a completely unexpected sector.

If medication for Parkinson's disease stops being effective, electrodes are sometimes implanted in a patient's brain. They are then stimulated electrically by a pacemaker, which temporarily switches off activity in a small part of the brain. It's very impressive to see how violent tremors suddenly stop when the patient switches on the stimulator. Yet this treatment is the result of serendipity, a lucky chance. In fact, it's not uncommon for advances in medicine to be made by accident, when a doctor or researcher is exploring an entirely different avenue. In 1952, a Parkinson's patient was set to undergo a drastic brain operation in a desperate attempt to stop his exceptionally severe tremors. The plan was to sever motoric pathways so as to paralyze the patient. During the operation, the surgeon, Irving Cooper, accidentally tore open a blood vessel. To stop the bleeding, the blood vessel was tied up, and the operation was abandoned. To everyone's surprise, the patient's tremors vanished. Cooper later went on to cauterize that blood vessel deliberately in other Parkinson's patients, thus disconnecting a small region of the brain. He succeeded in reducing tremor in 65 percent of Parkinson's patients and muscle rigidity in 75 percent. Subsequent experimental disconnection of different brain regions proved most successful in
the area below the thalamus, the subthalamic nucleus (
fig. 23
). This is where most electrodes are still inserted in the brains of Parkinson's patients. The nice thing about electrodes is that disconnection is reversible; as a result, you can see where they are most effective and can keep adjusting the way in which they are stimulated. This treatment alleviates symptoms like slowness of movement, muscle stiffness, and tremors, though it can't slow the progress of the disease.

Around thirty-five thousand people worldwide are going through life with depth electrodes in their brains. As in the case of any effective therapy, side effects have emerged. Some Parkinson's patients with depth electrodes have problems interacting with their partners and co-workers. Although most patients were personally very satisfied with the quality of their lives, their relatives sometimes reported that they were more irritable and prone to mood swings. Around 9 percent experienced psychiatric side effects like increased impulsiveness or crying fits. Electrode stimulation can exacerbate depression. We have even seen cases where the patient committed suicide, despite the electrodes having been implanted at the right location in the subthalamic nucleus. (Ten years ago, neurologists wouldn't have been interested in this correlation, but the boundary between neurology and psychiatry is fast becoming blurred.) Sometimes an implant can cause dementia symptoms because of bleeding or brain damage. But these symptoms occasionally disappear if the stimulator is configured differently. Cases have also been reported of psychosis, sexual disinhibition, and gambling addiction. One patient who had been a typical tightfisted Dutchman prior to the operation couldn't resist the lure of slot machines afterward. It was only years later, when his mounting debts forced him to sell his house, his wife demanded a divorce, and he tried to commit suicide, that the problem was brought to the attention of his doctors. (Gambling addiction can also be a side effect of the classic medication for Parkinson's, L-dopa, the dopamine system [
fig. 16
] being central to addiction.) Another patient treated with electrodes became manic and started buying houses in Spain and Turkey, something he really couldn't afford
to do. But he absolutely refused to have the stimulator switched off.

Electrode stimulation can also impair cognition, memory, and speech. However, most of the psychiatric side effects are temporary and easy to treat, and can even be prevented. They also tell us something about the function of brain structures and circuits in psychiatric symptoms, like the role of the dopamine system in addiction. The success of depth electrodes in treating Parkinson's has led to their application in many neurological and psychiatric disorders, like unbearable pain, cluster headache, depression, phobia, muscle spasm, self-mutilation, and obsessive-compulsive disorders. Studies are being carried out on the treatment of obesity and addiction using depth electrodes. At present, the possibilities seem endless. Irving Cooper could never have imagined all this when he accidentally caused a brain hemorrhage in 1952.

Depth electrodes were used to spectacular effect on a thirty-eight-year-old man who had been in a state of minimal consciousness for six years following an accident. He could occasionally communicate with eye or finger movements but never with speech. Under normal circumstances, recovery after twelve months in a state like that is virtually impossible. A breakthrough was made, however, when stimulation electrodes were planted on either side of the thalamus in the center of his brain, where sensory information is received. Within forty-eight hours of stimulation he woke up and would turn his head when someone spoke his name. Over a four-month period
of electrical stimulation he began to recover his speech, eat, drink, and comb his hair.