Deciphering the Miracles of the Mind

Pedaling his tricycle in a suburban cul-de-sac, 5-year-old Austin Rawnsley is rebuilding the most complex object in the known universe--his own brain.

With each revolution of the tricycle wheels, a living labyrinth of neurons fires to strengthen ties among brain cells that control his feet. Each time the steering wobbles, brain cells responsible for his hands respond in an expanding pattern of chemical and electrical signals that improve his dexterity.

As Austin chatters amiably, other neurons fire, linking words to concepts, and connecting both to the subtle movements of speech. He sees his mother and beams. Memories of this sunny day lodge in an intricate weave of cell signals, to be recalled instantly in a moment, a day or a decade.

This is the mental transformation that every child makes, crafting from three pounds of disorganized brain cells the trillions of neural connections, or synapses, that compose a human mind.

What makes Austin’s developing mind so remarkable is that so much of his brain is missing.

When he was 17 months old, surgeons at UCLA removed the left half to control his potentially lethal epileptic seizures.

Yet today, tests show that this mischievous boy in Agoura Hills--coaxed through years of painstaking physical, speech and cognitive therapy--appears to have regained almost all the abilities of a normal child. Only the stiffness of his right hand betrays the effects of extensive neurosurgery.

His brain has simply rewired itself.

Austin Rawnsley is a testament to the mystery inside every human skull.

His unusual recovery is a measure of what scientists are coming to understand about the adaptability and learning potential of every child’s brain.

More than ever, neuroscientists are discovering the dynamic nature of human awareness as it develops from infancy, how a handful of wet tissue learns to recognize loved ones, remember telephone numbers, perform differential equations and conceive dreams of paradise.

Experts in brain development say their new insights promise to transform everything from parenting, public education and programs designed to help preschool children to the ingredients of infant formula, which often lacks key fatty acids now considered essential to early brain development.

In their most crucial discoveries, researchers have learned that brain development in the first three years of life is more rapid, more malleable and far more extensive than anyone suspected. The brain remains a work in progress throughout childhood.

The developing brain is so robust it sometimes can overcome even severe physical trauma, yet so fragile that a mother’s prolonged depression can imprint her infant’s brain for a lifetime with the neurochemistry of sadness.

Their findings reveal the nature of learning--how neurons physically blossom in response to stimulation like a flower responding to sunlight--and the importance of critical periods in which the brain develops vision, language, muscle control, emotional response and reasoning ability.

So powerful is the enriching effect of learning on the physical structure of the brain’s cells that the brain of an active college graduate may have up to 40% more neural connections than that of a high school dropout.

The brain is so hungry for stimulation that, with proper attention early enough in life, scientists can raise a disadvantaged child’s IQ 30 points, cut the risk of some forms of mental retardation in half and correct common learning disabilities such as dyslexia. Conversely, denied proper stimulation, the brain atrophies, its neural connections withering like dying leaves.

The developing brain is so malleable it can incorporate behavioral problems into its circuits as readily as it might pick up a love of music, experts say.

For example, every newborn usually starts life with its brain’s neural circuitry brain preset to feel emotional well-being, new research indicates.

University of Washington researchers, however, discovered that a mother’s prolonged depression can change her infant’s brain, significantly reducing activity in the parts regulating joy, happiness and curiosity. The intimate interaction between mother and child is more than enough to condition the latter’s neural circuits.

And an infant raised in an atmosphere of fear or neglect is subjected to biochemical overdoses of stress hormones that alter the young brain’s circuitry, neuroscientists and psychologists have shown.

“Learning is anything that stimulates the brain over and over again,” said biophysicist Michael E. Phelps, who directs the Crump Institute of Biological Imaging at UCLA Medical School.

“It can be playing a musical instrument. It can be seizures.”

‘An Explosion’ of Knowledge

New ideas about brain development arise from a revolution in neuroscience, driven by advances in molecular biology, biophysics, chemistry, anatomy, neurology and computer science.

“There is an explosion in findings about the human brain,” said Antonio Damasio of the University of Iowa, an authority on the brain, language and cognition.

“We are at the brink of enormous breakthroughs in this area--developmental neurobiology--and there is no longer a boundary between biology, psychology, culture and education,” said Dr. Bennett L. Laventhal, an expert on child development and psychiatry at the University of Chicago.

Among the recent discoveries:

* There is no center of consciousness, no single clearinghouse for memory, no one place where information is processed, emotions generated or language stored. Instead, the human brain is a constantly changing constellation of relationships among billions of cells. Complex networks of neurons are linked by pathways forged, then continually revised, in response to experience.

* There is no way to separate the brain’s neural structure from the influence of the world that nurtures it. During growth and development, the feedback between the brain and its environment is so intimate that the two are essentially inseparable.

* There is no single, predetermined blueprint for the brain. More than half of all human genes--about 50,000--are somehow involved in laying the brain’s foundations, scientists have discovered. And they all exert a powerful influence over temperament, learning ability and personality.

People who inherit a longer than usual version of a gene responsible for how the brain absorbs the neurotransmitter dopamine, for example, tend to be more exploratory, excitable, extravagant and quick-tempered, researchers in Israel and at the National Institutes of Health recently discovered. A flaw in a second gene can leave a person unable to follow directions for assembling toys, or unable to follow a simple bus route, University of Utah researchers have found.

Even tiny variations in the timing of gene activity can have enormous effects on how the human brain develops.

Indeed, the fundamental intellectual capacity of all humanity rests on a three-day delay in the onset of a single gene’s activity that triggers the movement of neural cells from the tissues where they are created into their final positions in the maturing brain. That brief delay makes the cortex--the thin gray layer of brain tissue responsible for all higher thought processes--10 times larger, said Yale University neurobiologist Pasko Rakic. That is precisely the size difference between a monkey’s cortex and a human’s.

Despite the importance of genes, their effects can be overwhelmed by other influences.

Many genes involved in neural development do not become active until after birth. Even then, stress, chemical exposures and other conditions in the world in which they exist can alter what they do or whether they become active at all. Genes affecting behavioral traits are the most susceptible to environmental influences.

“The genes are the bricks and mortar to build a brain. The environment is the architect,” said Christine Hohmann, a neuroscientist at the Kennedy-Kriger Institute in Baltimore.

A Cycle of Stimulus, Response

In the beginning, there is a single cell.

From it eventually will grow the hand that rocks the cradle, the heart that dotes and the brain that will become the seat of reason.

For Austin and every growing child, the biology of learning shapes the brain’s anatomy and functional character.

In the womb, fetal brain cells multiply at a rate of about 250,000 a minute. By the time labor begins, every infant has already generated all the brain cells it will ever have, shaped by the genes that encoded their creation.

When an infant emerges from the womb, the brain is a structure of about 100 billion nerve cells arranged on scaffolding of more than 1 trillion supporting, thread-like glial cells. There are more than 1,000 types of neurons.

“Here is a system with an amazing number of components and it self-assembles--and when we are born, it works,” marveled UC San Diego embryologist Nicholas Spitzer.

At birth, however, the brain has barely begun the serious business of organizing itself. Its neurons, formed in the embryo during gestation, are not yet fully equipped, properly positioned or completely functional.

In a fever of creation, an infant generates up to 15,000 connections to each neuron during its first several years. As those neurons enlarge, with the axons and dendrites that tie them together developing 1,000 trillion interconnections, the brain quadruples in size.

Neural cells continue to migrate and position themselves in the cortex throughout the first two years.

In a remarkable cycle of stimulus and response, the budding brain builds itself, using the electricity generated by vision, smell, touch, hearing and taste to activate and organize the neural cells that make up its tissues.

Researchers long have known that the electrical activity of the neurons and the presence of special nurturing proteins--called neurotrophic factors--are necessary for the construction of the brain’s neural connections.

Until recently, they were not sure which led the way, leaving uncertainty over how important outside influences were in shaping the developing brain’s circuits.

Now, Stanford University researchers have shown that in order to be susceptible to the effects of the growth proteins, the neurons already must be activated.

“Fifteen years ago, everyone thought that each cell in the fetus was destined to a particular identity and location in the adult brain,” said Mary Beth Hatten, a developmental neurobiologist at The Rockefeller University in New York. She and her colleagues this year identified a gene involved in directing nerve cells as the brain grows.

“Now we know that migration is a part of how these neurons gain their identity and organize the brain’s architecture,” she said.

A slight misstep in neural development, however, can have profound consequences.

New research at UC Irvine and other universities suggests that disorders such as schizophrenia, autism and the kind of severe infantile epilepsy that affected Austin all may stem from problems that occurred when neurons ended up in the wrong places.

Starting about age 5--the birthday Austin celebrated in January--the brain hits a peak of activity it may never again achieve.

Pioneering research shows that between ages 3 and 8, a child’s brain has twice as many neurons, twice as many connections between them and is twice as energetic as an adult brain. This overproduction of neural matter is designed to ensure that the brain can adapt to any set of conditions. And it is just that overabundance of neural raw material that enables a mind like Austin’s to flourish in spite of the damage to the brain it inhabits.

As the child grows into a teenager, synapses that are not used are ruthlessly pruned--thousands per second. Only those that are reinforced by experience survive.

Taken together, the new insights emphasize a biological truth of human individuality: No two brains are physically alike, and the complex wiring of each brain is so unique that it is unlikely that any two people perceive the world in quite the same way.

In fact, no two infant brains are likely to respond identically to the care they receive.

“What one infant sees and senses and perceives is different than what another sees, senses and perceives,” said Dr. Bruce D. Perry, a brain expert at Baylor College of Medicine.

“Different kinds of experience lead to different brain structures.”

Going Into Overdrive

In the traditional view, the left side of the brain generally receives sensations and controls muscles on the right side of the body. It also controls much of speech and language in most people, while the right side of the brain handles more visual and spatial tasks, such as drawing three-dimensional shapes.

When it comes to human nature, the left side is believed to be more rational, logical and mathematical; the right side is more creative, emotional and artistic. Austin lost any inborn left-brain capacities on the operating table.

In a nine-hour operation, UCLA neurosurgeons removed his left temporal lobe and cut a three-inch swatch out of his central cortex. They severed the bundle of white nerve fibers that connects the right and left hemispheres and cut the neuronal connections. That cured the seizures.

Months after surgery, Austin could not stand unaided and could barely walk, even with his right leg in a brace. A second brace kept his impaired right hand from curling into a useless fist. He was left with a pattern of partitioned vision, as if he were looking through vertical Venetian blinds.

Child development specialists also said that because his constant seizures had so overwhelmed his developing personality, he had almost no cognitive experience: He had yet to understand simple concepts like cause and effect. He would not make eye contact. At age 2 1/2, he could speak no more than 10 words.

In the three years since Austin’s surgery, his parents and half a dozen therapists have forced his brain to reorganize itself by tutoring him for long hours every day in skills that other children learn more spontaneously--from coordinating eye-hand movements to walking and throwing a ball. They bullied the brain’s right side into taking over.

Brain scans of children who have undergone similar surgery show that the surviving hemisphere goes into overdrive, said brain expert Harry Chugani of Wayne State University in Detroit.

Today, Austin’s braces are gone. Only the scuff marks on the toes of his right shoe show that he ever dragged his foot.

“Every little thing that comes naturally with a child, we had to work on with him,” said his mother, Sharleen Schwartz-Rawnsley.

None of his therapists can say why Austin has regained so many normal functions. He is doing much better than children with similar medical histories. Certainly no adult would regain so much cognitive and motor ability. They do not know how much more he will recover.

The ability to form new neural connections through learning is most intense in childhood, but contrary to previous beliefs, the brain throughout life retains a remarkable ability to remodel itself physically in response to new experiences. Even though it may lose up to half its synapses by the time it reaches adulthood, it is still flexible enough to forge new connections between the cells that remain. On a more limited scale, the same sort of brain reorganization seems to be at work when patients are recovering motor skills after a stroke or develop some types of repetitive stress injuries, researchers at UC San Francisco, the University of Texas and UC San Diego say.

Texas health scientists discovered that when a stroke knocked out the part of the cortex responsible for use of the fingers, adjacent regions of the brain gradually compensated. In response to physical therapy, neural circuits devoted to the hand expanded into areas of the motor cortex that had control of the elbow and shoulder.

But overuse of an arm, wrist or hand may cause the portion of the cortex controlling it to enlarge and trigger an overload of signals that the brain perceives as pain. Working with owl monkeys, researchers at UC San Francisco were able to double the size of the cortex devoted to the fingertips in just 14 days. They quickly reached a point where a monkey no longer could use its hand due to the pain of overtraining.

Michael Merzanich, a UC San Francisco brain expert who conducted the research, said the effect of overtraining on the brain is a “catastrophic exaggeration” of how it normally adapts to learning. Nonetheless, it demonstrates how readily the brain can change its physical structure in response to training.

“Brains are powerful self-organizing machines,” he said. “It is easy to drive this great machine to change.”

Varied Experiences Stir Expansion

If overwork stresses a brain cell, boredom literally is fatal. In the absence of the proper stimulation, a brain cell will die.

But offer it a steady diet of enriched experiences and its neural synapses instantly sprout new branches and connections.

Tailor instruction to the properties of its neural circuits and the brain even can be trained to overcome learning disorders such as dyslexia, Rutgers University scientists recently showed.

Working with lab animals, Marian C. Diamond of UC Berkeley has demonstrated that early stimulation with toys in an enriched environment dramatically alters brain structure, resulting in greater branching of nerve cells, increased number of supporting glial cells, thicker capillaries and a thicker cortex.

Other researchers at the University of Illinois showed that stimulated lab animals developed 25% more synapses per nerve cell and 80% more blood vessels to nourish each cell.

Diamond found that novelty is key to sustained brain development. When she neglected to change the toys in her experiments quickly enough, the new brain connections in her laboratory animals atrophied almost as quickly as they had formed. Nurturing social relationships also were critical. Without them, the animals showed no increased brain growth, despite their special training.

Overcoming the consequences of an inattentive parent, the isolation of a hospital incubator or deliberate abuse does not come cheaply or easily.

Experimental educational programs designed to stimulate brain growth typically start about 6 weeks of age, run five days a week, 50 weeks a year, and cost about $10,000 per child. At the preschool level, teachers usually work with as few as four children at a time. Federal programs like Head Start may be too little, too late, many experts now believe.

“Intervening at kindergarten appears to provide only a minuscule benefit compared to intervention in the first weeks of life,” said Craig Ramey, a University of Alabama authority on the brain and childhood development.

“Most of America’s children are not getting the best of what we know,” said Marie M. Bristol, health scientist administrator at the National Institute of Child Health and Human Development.

“The brain is not fixed at birth. It can be changed,” she said. “Early intervention works, pure and simple.”

A ‘New’ Brain Studies an ‘Old’ One

Austin Rawnsley, curled up under a blanket on the family sofa, is watching himself on television.

He has been playing family videotapes taken during his infancy of the child he was before his neurosurgery, in an effort to understand himself better.

His new brain is studying his old brain.

Austin may have started asking some of humanity’s basic questions earlier than many children: Who am I? Where did I come from? Why am I different? And his answers may necessarily be more complex.

As he prepares to start kindergarten, they are questions that increasingly occupy his mind. How will he explain himself and his limitations to other children?

Through the kitchen doorway, his mother watched her son. She was made uneasy by his interest in what his therapists have worked so hard to put behind him.

“I wish to think he is pretty much who he would have been,” she said. “I have high hopes for him.

“I am on such a tightrope,” she said. “Cognitively, he is growing, growing, growing. In my heart--if no medical issues arise--there is no ceiling for this child.”

Austin’s therapists believe that his curiosity is healthy. In order to appreciate his strengths, he must come to terms with his weaknesses. And, they added, he must have an opportunity to mourn that part of himself he lost.

Indeed, his self-examination may be an encouraging sign of his recovery, signaling a crucial step in his mental development. In learning to understand himself, he may be developing the sophisticated cognitive, social and emotional tools necessary to understand those around him.

Whoever Austin is in the process of becoming, this lively personality arises from an accident of migrating neurons, a surgeon’s knife, intensive family care and the brain’s ability to rise above its physical limitations--something the 5-year-old already seemed to understand.

In the living room, Austin watched a videotape of his infant self sitting on his mother’s lap, paralyzed by a rapid succession of seizures. Then, viewing a tape about neurosurgery, he watched the surgeon peel back the muscular wrappings of the brain, revealing the soft, unplowed furrows within.

Austin tapped his own forehead.

“I am Austin,” he said. “This is fine for me.”

About This Series

Who are we? Where did we come from? While many scientists search for clues to these ultimate questions by probing the far reaches of the universe, others think the answers lie inside our own heads. Their probes are uncovering galaxies of neural cells, each twinkling with the brain’s life forces. As it orchestrates human behavior, this symphony of electrochemical communication may indeed constitute our very essence.

Today:

Brain development

Monday:

New technology is unveiling the brain’s prominent role in emotions.

Tuesday:

Brain researchers are overturning traditional ideas about mental illness.

Wednesday:

Poised at what may be the last frontier of science, researchers are trying to discover the nature of human consciousness.

This series will be available on The Times’ Internet site beginning Wednesday at: https://www.latimes.com/thebrain

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Neural Numbers:

Average number of human neurons: 100 billion

Number of octupus neurons: 170 million

Number of sea slug neurons: 20,000

Rate neurons are created during gestation: 250,000 per minute

Percentage lost to aging: 20 percent

Number of supporting glial cells: 10-50 times the number of neurons

Number of synapses for a typical neuron: up to 15,000

Diameter of neuron: 4 to 100 microns

Diameter of neuron nucleus: 3 to 18 microns

Processing speed of one neuron: one-thousandth of a second

Processing speed of a silicon chip: one-hundred-millionth of a second

Speed nerve impulse travels: 100 meters per second (200 mph)

Voltage of neural signal: 10-70 millivolts

Length of longest human axon: 3 feet

Length of longest Giraffe axon: 15 feet

HUMAN CEREBRAL CORTEX

Surface area: 2.5 sq.ft

Number of neurons: 2.6 billion

Cortical layers: 6

Thickness: 1.5-4.5 mm

BRAINS BY WEIGHT

Adult human: 1,300 - 1,400 grams

Newborn human: 350 - 400 grams

Pre-human ancestor: 850 - 1,000

Sperm whale: 7,800 grams

Elephant: 6,000 grams

Bottle-nosed dolphin: 1,500 grams

Chimpanzee: 420 grams

Dog (beagle): 72 grams

Cat: 30 grams

Hamster: 1.4 grams

Bullfrog: 0.24 grams

Watching the Brain at Work

Among the greatest advances in brain research recently is functional brain imaging. Unlike structural imaging (such as x-rays), which records anatomy, functional imaging allows scientists to watch the brain at work.

POSITRON EMISSION TOMOGRAPHY

PET uses radioactive tracers to track the brain’s use of energy. Mental activity is revealed as the tracers decay into gamma rays, which can be detected by a scanner.

The tracers are attached to sugar or water molecules, which are introduced into the bloodstream. As the tracers enter the brain, the subject performs a mental exercise or task. The PET scanner’s ring of detectors picks up the radioactive decay of the tracers.

As each positron decays, two gamma rays are emitted at 180 degree angles to each other. A powerful computer counts these gamma pairs and converts them into images of the brain’s energy use, showing the areas associated with the mental activity.

A PET scanner makes a series of slice-like images of the brain, which can be combined later to provide three-dimensional images from any angle.

FUNCTIONAL MAGNETIC RESONANCE IMAGING

FMRI is an increasingly popular innovation in brain scanning. It shows mental activity over shorter intervals than PET, with better anatomical detail, and does not require injection of radioactive tracers.

MRI makes structural pictures based on magnetic field changes throughout the brain. These changes are initiated by radio pulses that affect spinning hydrogen protons. Functional MRI makes images so quickly that changes in blood flow can be detected, indicating areas of activity. Water shows up particularly well, so organs like the brain, with a high water content, show up in great detail.

SOURCE: Scientific American