Starting from Zero

'WE CAN BUILD BETTER BRAINS' By ANNE McILROY

Saturday, Apr. 10, 2004 Globe and Mail

Monday is Brain Imaging Day at this exclusive Vancouver private school. The kindergarten class troops down to the assessment room, where one by one the boys and girls slip behind the curtain for a quick session in the magnetic resonance imaging machine. The MRI technician can quickly tell which regions of their brains are the most primed to learn that day. The results determine what each student will focus on that week improving their memories or spatial skills, or learning music, math or problem solving. It might be a good week for working on understanding facial expressions, or on a second or even third language.

Does this sound improbable? It's the future as imagined by Max Cynader, director of the Brain Research Centre at the University of British Columbia. "Forty or 50 years from now, a student will stick her head in a scanner and see what she could best learn that day," he says. "That's a dream. We aren't there, but we can see how to get to there from here." Dr. Cynader is an expert in what are known as critical windows times during which specific parts of the brain are the most ready to be altered and learn from experience. Scientists like Dr. Cynader believe that critical windows help to direct the development of visual skills and other senses such as smell and taste, as well as math, language and social skills in infants and children. They also may play a role in such learning disorders as dyslexia.

In the next 10 years, Dr. Cynader and his colleagues would like to put together a rough timeline of optimum brain development, to help parents and caregivers ensure that kids get the kind of stimulation they need when they need it. "It is exciting to think that we can train better people," he says. "That we can build better brains." There is no question that there are critical periods in the physical development of the human fetus that there is a set order in which the brain organs and limbs are built. If something, like the drug thalidomide, interferes with development on Day 28, then the arms don't grow and never will. But the role critical windows play in childhood brain development is less clear-cut, and more controversial.

Evidence has been slowly building since the 1970s, when a 13-year-old girl named Genie was rescued from the small California bedroom where she had been kept since she was 20 months old. She was bound to a potty chair and had no human contact except when her parents opened the door to feed her. Four years later, she had the vocabulary of a five-year-old, but could never get the hang of grammar. It seemed she had missed a critical window for language development.

Researchers have found other evidence of critical times for learning language or how to interpret the information that flows from our eyes to our brains, for instance in reading. But Dr. Cynader's work is different, because he is trying to pinpoint exactly what happens in the brain during critical windows; he wants to understand the architecture and find a biochemical signature that could easily be detected using modern brain-imaging techniques. Meanwhile, other researchers are charting which parts of the brain engage with math or with poetry, and which are used for getting jokes or irony. If they could combine that with the ability to measure when each bit of brain was at its most plastic, scientists might be able to tell if a child was better off studying, say, fractions or Spanish at any given time.

Dr. Cynader, an entrepreneur as well as a scientist, also hopes to find a way to recreate the state of the brain during critical windows, and maybe even synthesize a "smart juice" that could mimic and stimulate those natural mental peaks.

Thirty years ago, as a graduate student at the Massachusetts Institute of Technology, Dr. Cynader became intrigued by experiments being done by two neuroscience pioneers down the road at Harvard University. Torsten Wiesel and David Hubel weren't quite sure what they were looking for when they took a newborn kitten and sewed one of its eyes shut. Soon, though, they found evidence that closing one eye when an animal should be seeing the world for the first time fundamentally changes its brain, preventing brain cells from forming for vision in that eye: Even when they took the stitches out, the animal couldn't see. They repeated the experiment successfully with more kittens and then with monkeys, and the idea of a critical window in development was born.

Dr. Cynader began his own experiments, raising mice in an environment where they couldn't see anything move. With a strobe light as their only source of illumination, the mice were unable to see a cage mate scurry toward them. Instead, the other mouse suddenly appeared closer every 10 seconds. Normal mice have cells in their brains to analyze movement, but the strobe mice did not. They had missed a critical window. Today, he and his colleagues are hard at work in one of the most well-equipped neuroscience labs in the country, pinpointing exactly what is happening in rat brains when they are ready to learn to see. They are comparing the brains of rats reared in the dark and rats reared normally. Using the latest tools, they are zeroing in on the genes that are activated in the normal rats but not in the rats kept in darkness. They are slowly piecing together a biochemical picture of a critical period.

For now, they work with animals, but Dr. Cynader believes it is inevitable that it will be applied to humans. "If it is not us, it will be somebody else. There is no magic here." Like the half-blinded kittens, for instance, babies who have a cataract in one eye that isn't removed until they are 2 will never see out that eye. They have missed the critical window in which the brain learns to process information from both eyes. Taking this idea further, Daphne Maurer, a researcher at McMaster University in Hamilton, has studied and followed more than 200 children with cataracts. She has identified a critical window for learning to recognize faces at a distance.

Most adults, whether they realize it or not, look at the face as a configuration, she says. We know how far apart the eyes are, how far the eyes are from the nose and so on. But adults who had cataracts in both eyes when they were two-to-six-month-old babies never learn to recognize faces based on the distances between facial features. As a result, they have a harder time as adults recognizing someone across a crowded room. "Children who missed visual input for as little as the first two months never develop this expertise in spacing," Dr. Maurer says.

As a businessman, Dr. Cynader has already launched and sold two biotech companies that earned him millions. As a researcher, he is considered one of the best in his field by the Canadian Institutes for Advanced Research, which regularly brings together top researchers from around the globe to exchange ideas on early-childhood development. But some skeptics disagree with him, arguing that there may be important biological differences between learning to see and learning to speak a language. Dr. Cynader is gambling that the same basic process is at work whenever learning is involved.

Infants, for example, are born with the ability to understand sounds in any language phonemes that adult English speakers can't identify in Spanish, Hebrew or Mandarin. Babies lose that ability by about 10 months if they don't regularly hear someone speaking those languages. It is the same with baby talk: Babbling infants can produce the sounds of any language in the world, but lose that multilingual ability at six months. There, Dr. Cynader would argue, a critical window closes. Not all windows are so short or well-defined. It is easiest for children to learn a second language between birth and the age of 6, for instance. It becomes much harder after they turn 10 still possible, just not as easy.

"Look at Henry Kissinger and his brother," Dr. Cynader says. "He came to the new world when he was 11. His brother came when he was 8. His brother speaks unaccented English." A similar process is at work with complex motor skills, he says. In many sports, such as tennis or skiing, it is easy to tell who started as an adult and who learned as a child. So far, the evidence for critical windows is not strong enough to create consensus among neuroscientists. "I don't believe in those strictly defined critical periods," says Tomas Paus, a researcher at McGill University's Montreal Neurological Institute. He is involved in several brain-imaging projects to establish what is normal development in children's brains, including teenagers. "There are things of that nature, but [critical-windows researchers] over-generalize. They push it too far in thinking that you have three months, or between the age of 2 and 4, when you can wire up for this. One window for language. Another window for cognition. I don't think it is that simple. We are seeing that most of those functions develop continuously."

He argues that much of the evidence comes from animals or infants in extreme situations of deprivation being kept in the dark for months, for instance, because of cataracts or a researcher's curiosity. And Dr. Paus says he has seen too much variability in how children develop to accept that there are windows that open and close firmly at fixed periods of development. But Dr. Cynader agrees that critical windows do not suddenly snap shut. "The critical period isn't a set period of the brain. It is a state of the brain that correlates with activity," he says.

Mice who are kept in the dark for more than 27 weeks when their critical period for learning to see out of two eyes is over still manage to learn the skill once they come out of the dark, whether at six months or two years. But they will never learn to see as well as animals raised in a normal environment. In babies with cataracts, doctors now aggressively patch the good eye after surgery, to give the afflicted eye a chance to build its own network to the brain. In one hour, their eyesight is as good as that of a six-week-old baby. But as with the mice, human babies who had been deprived of sight in one eye never fully catch up. "There is a sleeper effect. Vision improves rapidly for six months, then there is slow improvement for six years," Dr. Maurer says. "The patients who had early deprivation hit a plateau at 21/2 , and they end up with a permanent deficit."

The fact that there is an optimal period for the development of certain skills doesn't mean that missing it would put those abilities forever out of reach. Still, critical windows are normally tied to a specific age, which is why Dr. Cynader is hoping to develop a timeline. He also agrees that every child will probably have slightly different windows of opportunity for learning. Girls may differ from boys. Birth order might have an impact. That's why he likes the idea of individual MRI scans to monitor brain development and learning opportunities.

Perhaps Dr. Cynader's most fascinating goal is to develop "smart juice" that mimics a hot learning zone in the brain. The first applications for this kind of discovery probably won't take place in schools, he says instead it may be to get "smart juice" somehow to patches of the brain that have been damaged by stroke or injury. This treatment would always have to be coupled with sophisticated training, but the possibilities for repairing damaged brains are tantalizing. Further along, it could also help healthy adults learn complex new skills, including learning to speak a new language, he says: "How about Urdu?"

But do the parents of the future, already anxious about whether their children will be ready for school, need the additional pressure of meeting multiple neurological deadlines? Should they be responsible for the architecture of their children's brains? Some scientists don't think so. Daniela O'Neill, a researcher at the University of Western Ontario in London, is so critical of critical windows that she argued forcefully that her work not be included in this article. She says the concept will give parents the wrong idea, and create added pressure to teach certain things to children at a specific time.

Dr. Cynader understands this anxiety. He brings out pictures of his three daughters. "This one," he says. "Why didn't I teach her Beethoven yesterday?" Other critics argue that just as babies are built to learn, parents are wired to help teach their children. That is why mothers all over the world speak in high-pitched voices to babies, stressing certain words "What a niiiccce baaaabeeeee!" to help infants learn their native tongue.

It may be that once we know more about critical windows, we'll find that parents intuitively know what their children are ready to learn. In fact, proponents argue that this research may actually convince some parents to lay off trying to teach children their alphabets or math too early. Yet Dr. Cynader acknowledges that his work touches on some explosive topics, and jokes about one day finding himself the subject of a National Enquirer story about "Frankensteinian" experiments.

In hunting for the genes that control critical windows, he is actually looking for the genes linked to learning, which may dictate whether a kid breezes through school or struggles to get through each day. Even researchers not interested in critical windows are searching for genes linked to behavioural or developmental problems, including attention deficit disorder. So far, they've identified 30 or more suspects. If their findings are confirmed, the next step could be testing kids for these genes. Right now, in the United States, you can walk into a handful of biotech start-ups in California, provide a few cells swabbed from the side of your cheek and get a look at what your future might hold.

Companies can screen DNA for dozens of gene variations that may mean it is more likely you will die from a heart attack, or get prostate or breast cancer. They can't tell you for sure what illnesses will be part of your future, only the probabilities based on the genes you inherited. It will be the same with the genes linked to learning. Would you want to know if your child is likely to succeed in school, or to be a troublemaker? Would it make a difference in whether you continued with a pregnancy, or in how you raised a given child? "It is a brave new world out there. There is going to be a lot of debate in Canada on this," Dr. Cynader says. As with genes linked to diseases, there is great uncertainty about what inheriting a particular developmental gene might mean. "Unfortunately, it is going to be too simplistic for quite a while. Let's say, for the sake of argument, that five years from now we publish our list of the great genes for learning. Ten years from now, someone else will say, `Well, they are only great at learning some things. Maybe they aren't creative. Or worse, maybe they are prone to cancer'."

New research is showing that parenting and environmental factors can make a difference in terms of whether having a particular gene will mean disaster for a child or not. Knowing what genes a child has is only one piece of information, not the whole picture. And no one child is going to get only the "good" variations and none of the potentially problematic ones. How children look and behave already plays a role in how teachers treat them. Genetic testing could lead to more discrimination in the classroom.

Peter Singer, an ethicist at the University of Toronto, says the best interests of the child must be the key principle: If a child is discovered to have these genes, what will be done to help? "There needs to be clear upside benefits to the individual child to make this testing appropriate. Following this principle is what will make the difference between a horrific Brave New World of classifying people by their 'genetic quality,' and the appropriate use of genetic testing to help the individual child," he says.

McGill University researcher Michael Meaney is an expert in how parental care can influence genes. He says only in extreme cases would knowing the developmental makeup of a child change the advice he would give to parents. That advice, he says, is to be as nurturing and caring as you can. There are also questions of social equity. If only the wealthy can afford genetic testing or regular brain imaging to help their kids achieve optimal learning, will that mean that kids from low-income families won't have a chance to compete against rich kids at school?

Dr. Cynader concedes there is a chance that his discoveries will never be put to use. Increased knowledge, he says, "is not always a good thing."

  On the other hand, this research could also lead to a way to treat learning disabilities such as dyslexia before a child even knows she is any different from her peers. That is certainly Dr. Cynader's hope. Dyslexia is the inability to read despite normal intelligence and instruction. If you take a nine-year-old with dyslexia, and give him a bunch of nonsense words like muf and gef, he won't recognize them because he hasn't memorized them. He hasn't learned to read in the same way that most people do. It is estimated that 3 to 12 per cent of the population has dyslexia. It can lead to low self-esteem and problems in school and later life.

Dr. Cynader's gut feeling is that dyslexia is a critical-windows problem one that involves how both the visual and auditory systems develop. Other researchers are taking different approaches, says Debbie Giaschi, an expert in dyslexia at UBC. She says Dr. Cynader's theory is promising but unproved.  To understand how he sees dyslexia, it is useful to go back to what actually happens in the brains of kittens and mice when scientists suture one of their eyes shut for a few weeks. Why do they lose the sight in that eye? The answer, according to Dr. Cynader, is ruthless competition: When the closed eye doesn't send any signals or input to the brain, the cells that had been transmitting information from that eye die. This is how the brain works. Information is transmitted neuron to neuron. Unused brain cells die. Dr. Cynader estimates children lose a third of their brain cells during the first two years of life. "It is a Darwinian world in there," he says.

What has happened in people with dyslexia, according to Dr. Cynader's theory, is that the cells needed to process rapidly changing sights and sounds have lost the competition to build connections in the brain. There is some evidence he may be right: American researchers have found that those cells don't seem to function as well in dyslexic patients, which may be why their brains fail to receive key information when they read. Working with others, Dr. Cynader's goal is to find a test to identify kids at risk for dyslexia when they are babies or toddlers. Researchers in Utah are zeroing in on a gene that may be linked to the condition in half of patients who get it. Others are working on hearing and sight tests that could detect the disorder early. The idea would be to develop a series of exercises that would strengthen the naturally weak part of their visual and auditory systems. This approach has worked in young animals.

"Let's try and fix them," Dr. Cynader says. "And if we are successful, they will never have a problem." Among all their other potentials, he says, critical windows offer a unique opportunity to repair damage: "If things go wrong during a critical period, you can make a mess. But if you want to fix things, the best time to fix things is a critical period, when there is still a lot of plasticity."

Anne McIlroy is The Globe and Mail's science reporter.



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