A RISTOTLE BELIEVED that the center for thought lies in the heart and that the brain helps cool the body. Drowsy people hang their heads, he said, because brain created heaviness forces the head downward. We laugh now, but many experts agreed with Aristotle as recently as the late 19th century. Indeed, we still know relatively little about the three pounds of flesh that makes us human.

This is not surprising given that the human brain, with its many billions of cells, is the most complex object in the known universe. But we have learned more in the past ten years than in all previous history, thanks to technologies that allow researchers to see inside living brains and examine brain functions at the subcellular level. That we have entered an era of extraordinary discovery becomes clear moments after I ring the doorbell of eight-year-old Matthew Simpson’s home in Albuquerque, New Mexico. The scene is a Hollywood version of how childhood is supposed to be: Bikes on the driveway, a green lawn, and next-door neighbors playing basketball.

Matt stands beside his mother as we chat on the porch. He can see that I am feeling the New Mexico heat. “Would you like a glass of water?” he asks. It is the last day of second grade, and Matt is proud of his report card. It shows respectable grades, good behavior, and steady improvement. Two years ago surgeons removed nearly half of Matt’s brain. Matt’s first three years were textbook normal. Just before his fourth birthday, he began to experience seizures—electrical misfirings that impede brain functions. Medicines did nothing as seizures threatened to turn fatal. The eventual diagnosis: Rasmussen’s encephalitis, a rare and incurable condition of unknown origin.

Desperation brought his parents, Jim and Valerie Simpson, to Ben Carson, a pediatric neurosurgeon at Johns Hopkins Hospital in Baltimore, Maryland. Carson recommended a hemispherectomy, removing the left hemisphere of Matt’s brain. Matt would lose half his cortex, tightly packed folds that handle thought processes and most of what makes us human. The empty area of the skull, Carson explained, would fill with cerebrospinal fluid at about a teaspoon every five minutes and would remain filled. The operation could lead to crippling, coma, death, or full recovery. Carson would not guess at odds. Nor would he say how much of Matt would remain with half his cortex gone.

Although hemispherectomies were performed in the 1940s, few patients lived. Pediatric neurosurgeons revitalized the procedure in the mid-1980s, because of advances in brain scans and in ability to combat bleeding. Several dozen hemispherectomies are performed each year now in the United States, usually as treatment for Rasmussen s encephalitis and forms of epilepsy that destroy the cortex but do not cross the groove separating left and right hemispheres. Patients can live because neither the disease nor the operation touches areas that control basic functions: the cerebellum, which coordinates movement; the diencephalon, which facilitates emotions and regulates body functions; and the brain stem, which maintains breathing, heart rate, and other life-support systems. As Matt began to suffer worsening seizures, sometimes every three minutes, the Simpsons had no choice.

Matt’s parents and half sisters, 16-year-old Stacy and 13-year-old Jamie, show me a scan of Matt’ s brain. I see the outline of a skull. One side has shapes in white, gray, and black. The other is all black, entirely filled with fluid. The operation left a scar that runs along one ear and disappears under his hair. But his face has no lopsidedness. The only visible effects of the operation are a slight limp and limited use of his right arm and hand. He also has no right peripheral vision in either eye. Matt and his mother drive out on errands. “I see a sailing ship and a huge elephant,” he says, looking at shapes in clouds. She discusses details with him and asks if he sees anything else. Matt describes a clown and a frog.

I appreciate such brain-stimulating games when I join his weekly session of speech and language therapy. One typical activity is word games. Therapist Joan Harden places cards in front of him. Matt turns one over. It says “fast things.” He must now name as many fast things as he can in 20 seconds. “Car ... truck.., train ... plane,” he says. The next card says “soft things.” Matt says “Butter. . .the middle of bread” and stops. A child his age should name from six to eight things each time. Matt names only four and two. Is this because he has half a brain or because he suffered seizures between ages 3 ½ and 6 ½. No one knows. In the past two months Matt has made nine months’ progress in language use. “In the improvement he has made it appears he is fostering and accelerating the growth of dendrites, threadlike extensions that grow out of neurons, the specialized cells of the nervous system,” Harden explains. “The neurons seem to be making better connections.”

More connections among the brain’s estimated hundred billion neurons mean a better functioning brain. Connections come from inherited growth patterns and in response to stimuli, including internal stimuli like imagined sensations. The body receives information at the “periphery”—the neuroscientists’ chauvinistic word for everything that is not the brain—and encodes it as nerve impulses. When these electrical impulses reach the brain, they trigger the release of messenger chemicals such as glutamate, which in turn induce electrical impulses as they travel from one neuron to another. This electrochemical process, the basis of brain communication, sometimes stimulates growth of new dendrites. Thus rats raised in cages full of toys have more brain mass—probably from more dendrites—than do rats in empty cages.

The brains of infants suffering from some forms of mental retardation have fewer dendrites than do the brains of healthy babies. Brain-imaging studies conducted by Harry T. Chugani, a pediatric neurologist at Children’s Hospital in Detroit, Michigan, suggest that dendrite production rises rapidly after birth and remains at a peak level from about age four to age ten. In fact, during these years a child’s brain has many more connections than does an adult’s and uses twice as much energy.

Until recently, experts believed that genes program most dendrite growth. People like Matt demonstrate that the brain has unexpected flexibility—what scientists call plasticity. This plasticity promises to redefine basic concepts. The left side of the brain of a right-handed person — precisely what was cut out of Matt—specializes in handling music, poetry, and mathematics. Yet Matt enjoys piano lessons, and math is his strongest subject in school. Somehow, knowledge and capability traveled from one side of his brain to the other.

Such transfers seem to defy biology. Does an undiscovered conduit exist, or does each side have dormant capacity to assume functions of the other? The ability to transfer is highest before adolescence, during the years of peak dendrite growth. But transfer, albeit limited and slow, also occurs when strokes kill portions of an adult brain. Other evidence of transfer comes after amputations. Every part of the body is connected to the cortex. Touching something with your left hand, for example, activates a particular part of your right cortex, and touching something with your right hand stimulates a mirror-image portion of your left cortex. Next to these sections of the cortex, for reasons no one understands, are areas connected to the nostrils. After his hand was amputated, one man reported tingling in his missing pinky when researchers dripped warm water under his nostrils. The part of his cortex connected to his nostrils had seized areas of the cortex that had received signals from the now missing fingers. Likewise, brain scans of Braille readers show that their reading fingers stimulate more cortical area than do fingers of sighted people. Presumably, extra use of these fingers prompts expansion into neighboring cortical territory.

The Simpson family says that Matt’s personality never changed through seizures and surgery—an observation made by most families whose children have had hemispherectomies. “He started as a nice, caring child and he stayed a nice, caring child,” Valerie says. For me, the best moment comes one evening while Matt is drawing with crayons and the adults are talking. Matt interrupts us. Jim asks him to stop. Interruptions continue. Jim warns Matt he will be punished. Matt persists. “Why are you smiling?” Jim asks me. “Because he acts like a normal eight-year-old,” I reply. “He is a normal eight-year-old,” says Jim.

M ANY PEOPLE LEARNED in school that we use only l0 % of our brains, a belief that may have been based on psychologist William James’s assertion in 1910 that we use “only a small part” of our mental powers. People like Matt certainly indicate that much of the brain is redundant. I can imagine Matt telling his dates ten years from now, “You won’t believe this, but I have half a brain. (You know the old one - ‘With half my brain tied behind my back.)

Matt’s resiliency is dramatic, yet no more so than a common occurrence: the development of new human brains. I look into a microscope at an eight-cell human pre-embryo, the product of laboratory, orin vitro, fertilization. The egg and sperm were taken from a husband and wife whose family history includes a fatal genetic disease. If scientists at the Illinois Masonic Medical Center in Chicago determine that this gene is not present, they will implant the pre-embryo into the mother. The pre-embryo resembles a transparent bubble floating in space. Although I feel like a voyeur, I cannot stop looking through the microscope. Each cell is rounded, the cell walls are thick lines, and dark smudges are cell nuclei—exactly what I expect. But why does each of the eight cells look exactly the same? Some will grow into the brain, others into the heart and skin. Maybe the microscope is not strong enough to reveal differences. “They are the same,” geneticist Yury Verlinsky explains. “From each of these cells, every cell in the body will grow. The differentiation begins once the cells have divided into about a hundred, about three days after the egg is fertilized. No one knows how it happens. There is no ‘master builder’ cell.”

D U RING EARLY PREGNANCY, neurons can grow at a rate of 250,000 a minute. Perhaps half die before a baby is born. This “pruning down” may eliminate flawed neural connections. Gerald Edelman, a neurobiologist at the Neuro-science Institute in La Jolla, California, sees a tropical rain forest in which “neural Darwinism” selects the fittest neurons. Whatever triggers brain development, it is the most sensitive part of fetal growth. Vitamin deficiency, maternal smoking, or prenatal exposure to alcohol, chemicals, or too much heat may prevent neural development or cause damage to neurons.

Women who have influenza while pregnant, some studies suggest, are more likely to have children who develop schizophrenia, as are women who suffer severe malnutrition during pregnancy. Other evidence, like family histories, indicates that inherited genetic malfunctions contribute to schizophrenia. Advancing knowledge about the role of the brain’s physical structure in mental illness should change our perceptions about such diseases. Including depression and manic depression, mental illnesses afflict more than 20 % of all Americans.

“That’s the frontal cortex of Steven Elmore, a 33-year-old schizophrenic,” says Dan Weinberger, a neurologist and psychiatrist at the National Institute of Mental Health, as he flips an image onto his computer. We are in the den of his home in Washington, D. C. Weinberger flips an image from Steve s identical twin, David —who is not schizophrenic—next to the first image. “Brains normally differ more from one another than do fingerprints,” Weinberger says. “But these brains are genetically identical and should look the same. They don’t.”

The differences between Steve’s and his brother’s are clear. Steve’s has less cortex and larger fluid-bearing ventricles. “The part of the cortex he’s missing,” Weinberger says, ‘‘serves as perhaps the most evolved part of the human brain. It performs complicated tasks such as thinking organized thoughts. This might help explain why paranoid delusions and hallucinations are characteristic of schizophrenia.

Weinberger clicks further into both brains. The images also show that Steve’s has a smaller hippocampus. The hippocampus, from Greek for “seahorse” because of its shape, facilitates memory storage. Such an abnormality may be why some schizophrenics have memory problems. “The loss of brain tissue does not worsen with time, and it does not improve with medication,” Weinberger says. “It may be there from birth, and it may be partly the product of genes that make a person vulnerable. It’s hard to know what’s really going on since schizophrenia doesn’t usually manifest until late adolescence.

Writing in the fourth century B.C., Hippocrates said that “madness” comes from too much “moistness” in the brain—exactly what Weinberger has just shown me. For Hippocrates, this was a lucky guess based on the belief that four “humors” —earth, fire, air, and water — control health. As is common when a scientific venture is in its infancy, discoveries raise more questions than they answer. How do genetic characteristics interact with environmental influences?” Weinberger asks me. “Why doesn’t schizophrenia appear sooner? Can we devise a way to treat patients before symptoms appear?”

Western medicine used to blame schizophrenia on upbringing or the patients’ self-indulgence. “Now at least we know it has physical aspects,” Weinberger says. “The same is true of manic depression and many other so-called mental illnesses.” Such insights have led to drugs that affect brain chemistry. Key to many of these drugs is dopamine, a naturally occurring chemical in the body that responds to external and internal stimuli by saying to neurons, “Attention must be paid.” Neurons have at least eight different types of receptors for dopamine; each absorbs a different message. Restricting the actions of dopamine reduces schizophrenic symptoms.

This physical aspect of schizophrenia should prompt changes in our attitudes— many people still see mental illness as a stigma—and in insurance policies that grant less coverage for mental illness.

W HATEVER THE CAUSE, about one in every hundred Americans— including as many as one-third of homeless adults—have schizophrenia. At a busy corner I see tell-=tale traits: Some homeless people stand alone and look particularly disheveled, strange even among the strange. One woman wears a wire-and-foil hat. “To keep my skull from opening,” she says.

What went wrong for these people? Lack of money and bad luck are likely suspects. About 40 % of Americans with severe mental illness receive no treatment - none.



June 1995, (pgs. 6-11)

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