It's about three pounds of wrinkled, pinkish-gray matter with the consistency of jelly -- and yet, in Emily Dickinson's words, "wider than the sky."
The human brain's nearly infinite reach comes from the elaborate circuitry of its billions of neurons -- a marvel that has led some to call it the world's most complex computer.
But scientists are zeroing in on another quality of the brain that distinguishes it from even the most powerful PC: its adaptability.
It turns out the brain is plastic.
Not that it's made of vinyl. Plastic in the sense of flexible and dynamic.
The brain is not a cerebral black box, wired forever by age 2 or 3, as once thought. It remodels itself constantly, in response to experience, aging, hormones, illness, injury, learning and countless signals from the world.
"Growth is an intrinsic property of the brain," said Ira Black, chairman of neuroscience at the Robert Wood Johnson Medical School in Piscataway, N.J. "The notion that the brain is not simply a hard-wired switchboard that can't be changed has led to a revolution in how we approach diseases of the brain or the mind."
Maranda Francisco, 18, is a dramatic example. Fourteen years ago, her life was being ruined by a rare form of epilepsy. Up to 120 seizures a day wracked her brain and threw the right side of her body into continual paralysis. At the age of 4, she was forgetting how to walk, talk, eat and learn.
Then surgeons at Johns Hopkins Hospital in Baltimore performed an operation called a radical hemispherectomy, removing the entire left side of Maranda's brain. Freed of the seizures, she made a stunning recovery. Her speech returned to normal, and she made up lost ground in grade school. Despite initial weakness, she regained nearly full use of her right arm and leg.
Today, Maranda is a senior in high school in the Minneapolis area. She leads a remarkably active teenage life--dancing, taking karate lessons, firing off e-mail--all because the right side of her brain took over for the missing left, assuming complete responsibility for her speech, memory, motor control and learning.
"Does function transfer? Sure," said John M. Freeman, director of the pediatric epilepsy center at Johns Hopkins. "How does it happen? I don't have any idea."
Decades before the current flourishing of brain research, Nobel Prize-winning British physiologist Charles Sherrington described the human brain as "an enchanted loom, where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern, though never an abiding one."
That unabiding pattern is part of what neuroscientists now call plasticity.
The idea of the brain as an ever-changing, dynamic organ should not have come as a surprise to neuroscientists, Black said. It is, after all, pretty intuitive. Tasks as commonplace as recalling a new friend's face or phone number cannot be performed until something changes in the brain.
"Any time you learn, you've changed the state of your brain," said Jordan Grafman, chief of the cognitive neurosciences section at the National Institute of Neurological Diseases and Stroke (NINDS) in Bethesda. "That's plasticity."
Neuroscience's 'Holy Grail'
The brain is like an incredibly detailed map of a constantly changing topography. "I always think of the Balkans--all those countries that have come and gone and changed their boundaries over the 20th century," Grafman said.
The new view has come partly from advances in neuroimaging techniques that allow scientists to see inside the living brain and "map" its shifting territories. Images from positron emission tomography (PET) and functional magnetic resonance imaging (MRI) enable scientists to track changes in the brain even as they occur. Activated areas of the brain "light up" on these scans, revealing increased blood flow and electrical energy.
The human brain has up to 100 billion nerve cells, or neurons, of which about 10 billion are in the neocortex, the outer layer of "gray matter" responsible for all forms of conscious experience. But brainpower comes from these cells' connections, the synapses where messages in the form of electrical pulses leap across gaps to help make sense of the world. Each neuron can form thousands of links, giving a typical brain 100 trillion synapses.
Synapses are reinforced with use, forming intricate circuits of knowledge and memory. As neuroscientists like to say, cells that wire together, fire together. The connections in an active adult brain become more numerous, complex and sophisticated--in a sense, "smarter."
A growing body of research in animals and humans over the past two decades has overturned what once was accepted as neurological dogma: that the brain operates like a circuit board, programmed by thousands of genes shortly before and soon after birth.
Among the findings:
* In blind people who learn Braille, the role of the visual cortex--the part of the brain that normally helps people see--is "invaded" and taken over by the sense of touch. Brain scans show that the reading finger in Braille readers "recruits" the unused visual cortex for its needs.
* As right-handed children learn to play the violin, cello or guitar, and are called upon to use the fingers of their left hand on the instrument's strings--a task involving dexterity--the part of the brain dedicated to processing signals from the left hand increases markedly. Brains scans show the expanding "cortical territory" of the left-hand fingers.
* In someone with an amputated finger, the sense of touch for that finger is partly taken over by the other fingers.
* The brain of a deaf person watching videos of people demonstrating sign language also reorganizes. In what Japanese researchers this year called "striking evidence of neural plasticity," brain scans in such a man showed that a part of the brain normally used for hearing and understanding spoken language was recruited to help him decipher sign language.
All this evidence "has led us to believe that how you use your brain physically helps determine how the brain is organized," said Guy McKhann, director of the Mind/Brain Institute at Johns Hopkins University. "The brain is much more plastic than we thought."
The new findings are tantalizing. If the brain can figure out ways of reorganizing itself to recover lost or damaged functions, this offers tremendous hope for better treatments of stroke, epilepsy, Alzheimer's disease, Parkinson's disease and spinal cord injury. Yet medicine's knowledge of how to spur this kind of brain reorganization is still primitive.
Why one stroke patient, for example, regains use of the left hand, while another doesn't, remains largely a mystery, McKhann said. If scientists knew the answer, they'd be closer to solving the next big challenge: how to promote such recovery in stroke patients and others.
Once scientists understand how the brain accomplishes its plasticity, they may be able to develop more effective therapies--such as drugs or physical exercises that mimic or enhance the natural process.
Plasticity's implications touch "virtually every major category of human illness, from mental retardation at one end of the age spectrum to senility and Alzheimer's at the other," Black said.
Recovery of function--how the brain repairs or limits the damage from a major illness or injury--has become the overriding challenge for neuroscience, said Edward Taub, a behavioral brain scientist at the University of Alabama at Birmingham. "It's almost like the Holy Grail."
The drastic surgery that cured Maranda Francisco's epilepsy has been performed on about 80 children at Johns Hopkins over the past 15 years.
In carefully selected young patients, neurologist Freeman said, the hemispherectomy can improve lives by ridding them of disabling seizures without causing unacceptable brain damage. "It's better to have no hemisphere than to have a dysfunctional hemisphere," he said. "When you take out the bad one, the good one finds new pathways."
The remarkable plasticity that allows the operation to work has "vast implications" for eventual treatment of other brain illnesses, Freeman said.
"All of these things are sort of works in progress."
'A Real Trickster'
When a leg is amputated or disabled by a stroke, suddenly the brain no longer can receive signals from it. That part of the cortex goes silent, useless.
"What does the brain do when part of itself is silent?" said Lucien M. Levy, a neuroradiologist and chief of the spectroscopy unit at NINDS. "It basically reorganizes--just like any big organization. Like the NIH!"
In the reorganization, the silent parts are recruited for another purpose. Doctors used to think of the nervous system as fixed, so that "if you lose brain cells, that's it," Levy said. "But the more we look at it, the more we learn that the brain can adapt and reorganize itself."
That's where the analogy between the brain and the computer breaks down. A hard-wired computer adapts only if you change its software. "But in the human brain, the hard wiring itself changes," Levy said.
The brain, in other words, is a computer that can learn.
A computer can be programmed to play chess by recognizing the patterns of play. But its expertise is limited to bits of data governed by the rules of the chessboard.
Humans, because they have brains instead of a microchip, look at a chessboard differently, McKhann said. They see a king, for example, and think of a castle in Scotland--which in turn reminds them of a music festival in Edinburgh.
"It's that kind of activity that our brains do all the time," McKhann said, "and that a computer can't do." Plus, each brain is unique. "You might think of the Edinburgh music festival, and I might think of a local pub."
The brain's built-in plasticity helps it respond quickly to new demands--from memorizing a phone number to practicing the violin--or setbacks like the loss of a limb.
"You cannot have a brain without [plasticity]," said Alvaro Pascual-Leone, a neuroscientist at Harvard Medical School and director of behavioral neurology at Beth Israel Deaconess Medical Center in Boston. "That's why the analogy with the computer is not a good one."
The brain's ability to adapt has limits, of course. Normal plasticity cannot fully compensate for a severe "insult" to the brain, such as a damaging head injury, tumor or stroke.
Plasticity in the brain can also go awry, overreacting to a stimulus or reacting in a chaotic way. It leads amputees to feel "phantom pain" in a missing leg, as impulses from nerves in the remaining stump are misinterpreted as coming from the amputated limb. Writer's cramp and musician's cramp are forms of a repetitive stress injury that results from brain plasticity--when an often-repeated motion is learned so well that the fingers cannot unlearn it to perform other routine tasks.
And no one would want the brain to become totally plastic. Then, instead of relying of memory and habit, it would be constantly reorganizing even in response to the most trivial experiences--with chaotic results.
When the brain tries to make up for an injury by shifting the operations of the damaged area to an unaffected area, the compensation sometimes comes with a cost--a kind of neurological traffic jam.
NINDS's Grafman recalls an adolescent boy who had suffered a severe brain injury when he was very young. The injury destroyed much of the boy's right parietal lobe, including the part of the brain involved in spatial processing, which helps people locate themselves in the world and keep a sense of direction. By the time Grafman saw him, the boy had made substantial progress in navigating his way through daily life, as the left side of his brain apparently had taken over part of the right's responsibility.
But the recovery had a price. The boy now had serious difficulty using numbers or making simple calculations. Apparently the spatial location function had crowded out his mathematical ability from the left side of the brain. There wasn't room for both.
Another form of brain plasticity involves what Grafman calls a "compensatory masquerade." For example, people use different strategies, without even being aware of it, when driving from home to work. One person may rely mainly on street signs, following their explicit verbal cues. Another may rely more on a general sense of direction and spatial location, without reading specific signs. If a brain injury harms one ability--the sign-reading capacity or the more general sense of spatial location--the brain may shift to the other approach, enabling the person to navigate the route. But the brain's ability to shift strategies may simply mask the damage, misleading a patient or family to underestimate the injury.
"The brain is a real trickster," Grafman said.
One of Pascual-Leone's patients was a man who loved to paint pictures. The man suffered a stroke in his fifties and suddenly was unable to speak or move his right hand. His speech returned by the time he left the hospital, but it was only with great difficulty and long rehabilitation that he gradually recovered the ability to manipulate a paintbrush with his right hand.
That progress, however, left a bizarre result: The man could no longer speak and paint at the same time.
A PET scan showed that both speech and hand movement had relocated in his brain--and now occupied the same exact site on the cortical map.
"The brain was struggling to find other ways to get his hand to move and his voice to work properly," Pascual-Leone said.
Plasticity also plays a role after more mundane injuries. Within minutes after a broken leg is set and immobilized in a plaster cast, the part of the brain representing the leg starts to reorganize. It's as if the brain said: "I don't need the brain cells for that leg anymore, so I'll use them for something else."
What intrigues neuroscientists is that immobilizing the leg appears to affect the brain even before the muscles start to wither from lack of use. Finding a way to prolong activity in that part of the brain--the part controlling the leg--might help "shorten the rehabilitation down the road," said Pascual-Leone.
'A House With a Gazillion Doors'
Plasticity gives new meaning to the maxim, "Use it or lose it."
Within limits, the human brain has the capacity to remodel itself at any age, said Michael M. Merzenich, a brain scientist at the University of California at San Francisco. Merzenich's tests on monkeys in the 1980s provided some of the most compelling early evidence of brain plasticity.
All experience, good and bad, drives the brain's continual remodeling, Merzenich said. Even illness or injury can be seen as a kind of "learning" for the brain. The ultimate therapy for a degenerative disease like Parkinson's, which embeds itself harmfully in the brain, Merzenich suggested, may come not from a pill but from an intense adaptive "learning" process that somehow helps the patient "unlearn" the illness.
Human learning, Merzenich said, is "lifelong and continuous."
Yet as the Baby Boom generation is discovering, remodeling is more difficult in an adult brain than in a child's. Some kinds of learning do get harder, and memory does deteriorate with aging. Even the old saw, "You never forget how to ride a bicycle," is not perfectly true. (You may not fall off, Merzenich said, but you probably won't ride as well as you did as a child unless you keep practicing.)
The study of children learning to play the violin showed that the changes in their brains were greatest in those under age 13. And the hemispherectomy surgery that can cure severe epilepsy in some children would be unethical in an adult because of the severe and irreparable brain damage it would wreak.
"The younger you are, the more plasticity can work," Grafman said. "The hemisphere is less 'committed.' There's less knowledge in there. There's more room for these new connections to emerge."
While there is some physical deterioration and loss of memory in the adult brain over time, a bigger impediment to continued learning is the patterning that already occupies the brain.
Consider a person learning a second language. Every language has its own distinctive sound patterns, and in trying to learn new words, the brain goes through trial-and-error guesses based on knowledge of the first language. The older the student, the more "embedded" the first language is, and the harder it is to override expectations about what a new language will sound like.
"It's not that the brain is full," Merzenich said. "It's that the brain operations around the first language are so powerfully embedded that it impedes your ability to learn the second."
"Imagine," said Pascual-Leone, "a house with a gazillion doors." He was trying to describe the adult brain.
The often-used doors in this mansion are kept unlocked or even open, with easy access and a free pathway. But with the passage of time, unused doors stay closed or blocked and eventually get stuck.
Is it possible to reopen a door that has been stuck closed for years? "Sure," he said, "but you may have to call a contractor."
The loss of brain cells, contrary to popular belief, is not the hallmark of aging--or the reason doors get stuck. For better and for worse, it's more complicated. Aging involves constant gain and loss, the brain's shifting synaptic patterns that reminded Sherrington of "an enchanted loom" and Pascual-Leone of the doorways in an infinite house.
As a mentally active person gets older, Pascual-Leone said, the connections between nerve cells become more numerous and far-flung. "They have more breadth and sophistication."
Perhaps this is what enabled artists like Monet, Picasso and Georgia O'Keeffe to keep reinventing themselves throughout long productive lives.
Neurons have branches, like trees. Each time a nerve cell branches out, it allows for more subtle connections with other faraway neurons, not just the nearby ones that do similar things. That gives the mind of an adult more reach and richness, a larger view of the world.
"So even though you may lose some of the details [as you age]," Pascual-Leone said, "you get the big picture.
"Maybe that is wisdom."
Mysteries of the Brain
This year marks the end of the "Decade of the Brain," proclaimed by President George Bush in 1990. With more powerful imaging devices and new genetic information, scientists are exploring the secrets of the organ that makes humans unique. This is the first of several articles in Health about mysteries of the brain.
Anatomy of the Brain
The brain has three main parts:
The brain stem, which connects the central brain to the spinal cord and controls breathing and heartbeat.
The cerebellum, a twin-lobed oval structure behind the brain stem, which coordinates movement and balance.
The cerebrum, the largest part, which consists of left and right hemispheres joined by a bundle of nerve fibers called the corpus callosum. The outer layer of the cerebral hemispheres -- the cortex, or "gray matter" -- is responsible for all conscious experience, including thought and feeling.
Different parts of the cerebrum are involved in different functions. The left hemisphere, for example, specializes in speech, language and numerical calculation; the right, in the five senses and recognition of patterns.
SOURCES: American Medical Association and the Society for Neuroscience
CAPTION: 'The brain is a real trickster,' says neuroscientist Jordan Grafman, referring to its dazzling ability to compensate for injury and keep functioning.
CAPTION: Two MRI images show how the brain can reorganize. Top scan is of a sighted person reading a word by touch in Braille. The bright spots (indicating brain activity) are in the area specializing in touch. Bottom scan, of a blind person reading the same word in Braille, shows more of the brain involved, including areas that process visual information in a sighted person.