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A Tale of Two Brains
How and why do men and women think differently? Researchers at the Medical School uncovered some clues during work on how both sexes learn to read.

When Yale physicians Bennett and Sally Shaywitz enticed a group of right-handed, 20-somethings—19 men and 19 women—to spend an hour answering questions inside a magnetic resonance imaging (MRI) machine, the objective of the husband-and-wife research team was clear enough. The Shaywitzes, codirectors of the Center for the Study of Learning and Attention Disorders—a National Institutes of Health–funded program at the Medical School—were attempting to locate the precise areas in the brain where some of the fundamental processes involved in reading take place. And although they found what they were seeking, they also discovered, as often happens in basic research, something more than what they were looking for: hard evidence that male and female brains don’t work the same way.

“We were very surprised,” said neurologist Bennett Shaywitz. “There had been suggestions in the past that the brain organization of men and women might be different, but this is the first time that anyone has been able to look at the brain at the same time an individual is performing a task.”

For their study, the results of which attracted front-page attention around the world last spring, the Shaywitzes monitored subjects while they engaged in four tasks. Initially, each person was shown two sets of lines and asked to indicate whether they were the same or different (in all the experiments, the subject squeezed a hand-held bulb to signal similarity and did not squeeze the bulb if the pairs in question were dissimilar in any way). Next, the subject viewed two series of letters and was asked if the pattern of upper- and lowercase letters was the same or not. The third task involved comparing pairs of nonsense words, such as “Leet” and “Keat,” and “Leet” and “Joat,” to determine if they rhymed. Finally, subjects were asked if word pairs belonged to the same category: “car” and “bus,” as opposed to “car” and “oak.”

While each task was designed to measure different aspects of the reading process, the rhyming assignment, which required the subject to sound out the nonsense words, was of particular interest to the Shaywitzes, who have been studying learning disabilities for more than 20 years. “In 1978, I was asked to start a program and clinic at Yale,” says Sally Shaywitz, who explains that her interest in the subject had been piqued by her experiences as a behavioral pediatrician. At the time, physicians who attempted to help children with learning disabilities were faced with, the researcher said, “a tremendous void of information.”

To help rectify the situation, Sally Shaywitz, who often collaborates on research with her husband, began the Connecticut Longitudinal Study. This long-term project, which was started in 1983 and is the most extensive investigation of its kind, has provided an in-depth look at a representative sample of Connecticut schoolchildren who, at the study’s inception, were in kindergarten. “There were 445 kids at the start, and we’re still following 408, who are now living in 26 states and four foreign countries,” she says. “The study has been enormously helpful in providing information on the epidemiology of learning and behavior.”

One key finding, reported in 1990 in the Journal of the American Medical Association, debunked a longstanding belief that reading problems, which comprise more than 80 percent of all learning disabilities, primarily affect males. “In the scientific literature, researchers commonly reported that four times as many boys as girls were identified as having this difficulty,” he explains. “But when we actually tested every child, we found that there were equal numbers of boys and girls with reading disabilities.”

In other studies, the researchers have shown that among people who have trouble reading, the root cause is generally the would-be reader’s inability to break words into a series of basic sounds, called phonemes (there are 44 in English). “You can think of phonemes as the currency of our language,” says Sally Shaywitz. “All the transactions in the nervous system involving language take place via the phoneme.”

Consider the word ‘bat,’ for example. It’s made up of three phonemes—‘buh,’ ‘ah,’ and ‘tuh’—and when a person hears that combination of sounds, the brain automatically puts them together in a word that may mean, depending on the surrounding words, an implement for striking a baseball, or a mammal that flies by night. “When young children are beginning to read, they learn that the letters they’re seeing which make up the word on the page have the same number of sound units in the same pattern as the word they hear,” says Sally Shaywitz. “And when they make that connection, we say they’ve mastered the alphabetic principle and broken the reading code. Once that happens, the ability to read takes off.”

For about 20 percent of the population, however, reading is an ongoing struggle. The Shaywitzes, among others, have determined that most often, the problem lies in what researchers call phonological processing. In essence, those affected cannot make the connection between the printed word and its sound structure.

In order to find out where the difficulty takes place in the brain, the scientists and their colleagues at the Medical School and at the Haskins Laboratory in New Haven had to first learn how the brains of people adept at reading handled the necessary tasks. Only within the last couple of years has such research become possible, notes John Gore, professor of both diagnostic radiology and applied physics. Gore, who directs an MRI research program at the Medical School and has collaborated with the Shaywitzes on their work, explains that until quite recently, most of what has been learned about the inner workings of the brain has been an offshoot of neurosurgery. With a patient on the operating table, researchers would, using electrodes and minute amounts of electrical current, stimulate various parts of the brain to determine which parts controlled specific bodily functions. Another widely used method for creating a mental map, says Gore, has been to chart how neural disorders such as strokes, tumors, and cerebral hemorrhages affect the body.

What has eluded scientists is the ability to watch the brain at work, but recently, Gore and his Yale colleagues have figured out how to use MRI, a method of providing startlingly clear images of tissues like those surrounding the knee and the shoulder—tissues that are nearly invisible on X-rays—for a kind of high-tech mind-reading.

“The key here is speed,” says Gore, noting that creating an MRI picture normally takes between seconds and minutes. “But with new hardware and software, we can now get an image in as little as 25 milliseconds.”

Gore’s team has come up with a way to put together and analyze the rapid-fire snapshots that result from what is called “echo-planar functional magnetic resonance imaging,” and using this methodology, researchers at the University and elsewhere can now observe changes in cerebral blood-flow patterns and oxygen concentrations, both of which ebb and flow in concert with mental activity and the physical processes under the brain’s control.

Scientists at Yale and elsewhere have quickly embraced the technique. Last year, in one of the first studies to exploit echo-planar imaging, Robert Shulman, professor of molecular biophysics and biochemistry, watched thoughts take shape as subjects were given a noun for which they had to come up with a related verb. Neurosurgeon Dennis Spencer, the Nixdorf-German Professor of Surgery, now uses the MRI snapshots to guide his scalpel away from particularly sensitive areas of the brain.

There are projects underway to understand the neurobiology of finger tapping, the perception of faces and of smells, and the way in which the brain pays attention—or, in the case of disorders like Tourette’s syndrome, can’t pay complete attention—to the world. In an ongoing investigation, Patricia Goldman-Rakic, professor of neuroscience, has used echo-planar functional MRI to search for the site in the brain where a particularly critical function called “working memory” occurs. In May, Goldman-Rakic announced that she and her colleagues had found the place where people actually keep something in mind. It turns out that working memory, which the researcher termed the “mental glue that links a thought through time from its beginning to its end,” occurs in clusters of specialized cells located in the prefrontal cortex, a region of the brain just behind the forehead.

But what has attracted all the attention is the collateral discovery of identifiable differences in the way male and female brains operate. “This method is like a dream come true for investigators,” says Bennett Shaywitz, pointing to a composite echo-planar functional MRI image taken while men and women were engaged in phonological processing. The picture told a tale of two very different brains. Those of the males in the study showed an activation pattern centered in a region known as the left inferior frontal gyrus. “This area was described over 100 years ago by Paul Broca, a pioneering French neurologist,” says Shaywitz, “and we’ve since learned that ‘Broca’s area’ is critical to performing tasks involved in language.”

The act of sounding out phonemes triggered strong activity in this region, and the pattern heartened the researchers, because it occurred exactly where previous studies had said that it should. This correspondence gave investigators confidence in the technique. But when the Shaywitzes looked at the brain activation activity of females involved in rhyming phonemes, the researchers found a very different pattern: Among women, not only does the left inferior frontal gyrus come into play, but a comparable area on the right side of the brain also springs into action.

Intriguingly, the difference in mental geography does not translate into a difference in ability. “It isn’t a matter of men or women being better at this task,” says Sally Shaywitz. “In fact, they’re identical in terms of speed and accuracy.”

There was, however, earlier evidence of sexual inequality that might have prepared the researchers for their finding. “When women have a stroke that involves the left side of the brain, their verbal functioning is less impaired and they tend to recover better than men do,” says Bennett Shaywitz. “So if language is a critical component of brain functioning, you’d think that evolution would have built the apparently protective redundancy we see in women into the brains of both sexes. No one has a good explanation for its absence in men.”

Whatever the reason, the next step in their investigation is to use echo-planar functional MRI to examine the neural activity patterns of people with reading disabilities while they perform a group of tasks similar to those engaged in by the Shaywitzes’ non-reading-disabled subjects. That study is currently underway, but it will take several months to analyze the data. However, given what the researchers have already learned about the nature and location of this disorder, they expect to find significant differences between the two groups.

“A reading disability often reflects a very specific deficit surrounded by a sea of strengths,” the scientists note. “A problem in phonological processing means you can’t decode words, but if all the higher-level language processes involved in comprehension are intact, then you can use context to get at the meaning of the word. It just takes more time.”

And, perhaps, other parts of the brain.

“The lesson in our work is that you can use different routes to get at the same result,” says Sally Shaywitz. “The brain is much more versatile and flexible than we’d ever imagined.”

But for people affected by reading disabilities, this powerful new method of watching the mind at work also has major clinical implications. “We now have a sense that reading disabilities have become real,” she says, adding that it may eventually be possible to hold up an MRI and tell an individual the nature of the problem. “That excites us as both physicians and scientists, because it means we can also begin to use this technology to design strategies for intervention.”

In the near future, the Shaywitzes plan to take echo-planar functional MRI pictures of children with reading disorders—their work has shown the researchers, along with anyone else interested in pursuing similar studies, the importance of including girls in the investigation (and keeping the girls’ MRI images separate from those of the boys)—and then teach their subjects more effective ways to read. The scientists will later take additional snapshots of the children’s brains to see if successful education results in any changes, either short- or long-term, in the inner workings of the mind.

“We now have the key to understanding reading disabilities at the most basic level,” say the Shaywitzes. “For the first time, a problem that has been so puzzling all makes sense, and we’re on the verge of being able to do something about it.”  the end

 
     
   
 
 
 
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