BIOFEEDBACK NEWS

June 10, 2000
A Scalpel, a Life and Language

• The brain's sites for nouns, verbs and concepts remerge as a cancer patient answers questions during surgery.

By Robert Lee Hotz,
TIMES SCIENCE WRITER

In every human thought and reflection, there is a word.

For Paul Sailer, the essence of all his words is concealed in the cells along a pastel furrow of brain tissue behind his ear, just to the left of the surgeon's probe.

On this day. Sailer, 32, lies on an operating table with his head clamped firmly in a surgical vise, in a subbasement of the UCLA Medical Center. His skull is open. His brain pulses as he breathes. The ex­posed tissue steams in the cool dry air. 

A brain tumor is slowly crushing his left temporal lobe and with his capacity to make sense of words and sentences.

Only a few weeks before, Sadler, a newly wed electrical engineer at Point Mugu Naval Station, was in training for a mountain bike marathon.

Now, to save his life, Sailer must risk the uniquely human ability to express his thoughts. The surgeon's chance of preserving life and words de­pends on a revolution in neurobiology that for the first time Is revealing exactly where nouns, verbs, sentences and the concepts they articulate are rooted in the brain.

In this moment, everything that science has learned about the human brain and its most com­plex behavior is concentrated in a surgeon's hands, a psychologist's probing questions and the courage of a young man on an operating table.

On the surface, the tumor cells in Sailer's brain look no different than normal tissue. There is no language organ in the brain and no easily discemible tissue where words or grammar reside. There are only microscopic threads of cells and synapses.

Senior surgeons schooled in the anatomical short­hand of the body, with its emphasis on clearly de­fine the organs, nerves and circulatory systems, this profound decentralization almost comes as a shock. Language is nowhere and yet everywhere. But a high-speed brain scanner at UCLA, used during pre-surgical planning to image mental activ­ity, can see what the human eye cannot. It reveals the cells in Sailer's brain that are respon­sible for language—"eloquent cells," his surgeon calls them—as a constellation of pinpoints of light; the tumor as a shadow across a swath of brain tissue.

In one crucial area, the shadow has em­braced the light.

When this operation is over, some por­tion of those eloquent cells will be gone. But without the operation, the unchecked growth of the tumor could easily silence Sailer's mind well before it proves physi­cally fatal.

The decisions made during the next 9 hours by the surgeon, Dr. Gregory J. Rubino, are choices measured in millimeters. They may not only save Sailer's life, but also salvage his link to the world around him, his ability to give form to his inner­most thoughts and emotions. The opera­tion may save what some believe is the foundation of the conscious mind itself—its ability, through language, to shape its own inner dialogue, to know itself.

The Imperative of Expression

Bees dance. Whales sing.

At a loss for words, baboons employ a rich vocabulary of curtsy and bow. Even bacteria can signal their intentions with the crude semaphores of primordial chem­istry.

Indeed, nature has given almost every creature a way to get its meaning across;

yet only human beings are endowed with such a complex and elaborate means of making their desires known.

Without a stumble, the average person can produce about 150 words a minute, each word selected in milliseconds from as many as 50,000 possibilities and arranged in a meaningful sequence dictated by an elaborate mental stylebook of grammar and syntax.

So powerful is human language as an en­gine of thought that, by one computer esti­mate, it would take 10 trillion years just to speak all the possible English sentences of no more than 20 words.

Armed with new insights into the cel­lular structure of thought, researchers are beginning to understand that the marriage of meaning—as expressed through language—and the human brain is far more intricate than anyone had imagined.

Not so long ago, the ability to communi­cate seemed a relatively simple matter of anatomy.

  Based on studies of brain injuries, re­searchers knew that people who damaged part of the frontal lobe called Broca's area could understand language but could not speak fluently. Conversely, those who damaged a region of the temporal lobe called Wernicke's area could speak easily enough. What they could say, however, was virtually meaningless.

But recent research indicates a far more complex picture. Exploring the neural mechanisms underlying everyday speech, researchers at the University of Iowa Col­lege of Medicine and the Salk Institute for Biological Studies in La Jolla recently dis­covered that the brain retrieves words to describe the world around it through a kind of interactive mental dictionary dis­persed in many separate parts of the left cerebral hemisphere.

Additional networks throughout the brain are activated to help locate and re­trieve the different kinds of information that add up to the meaning, construction and pronunciation of a noun. Verbs are or­chestrated by entirely separate networks of neurons.

The more complicated the grammar of a sentence, the larger the amount of brain tissue pressed into service, Carne­gie Mellon University researchers have determined. The mental machinery of language triggers activity in both halves of the brain, whether words trip off the tongue or are signed on the hands, re­search shows.

"Language is a dynamo," says neuro-linguist Ursula Beluggi at the Salk Insti­tute.

No one knows just when the human spe­cies uttered its first words or what trig­gered the evolution of its language ability, any more than individuals can recall that time in their lives before they learned to speak. Without words to give them sub­stance, what form could such memories have?

Helen Keller, the noted educator who was deaf, mute and blind from the age of 16 months, did not learn her first word until she was 7. She later described her isolated, wordless inner world as "an unconscious but conscious time of nothingness ... a dark, silent imprisonment. I did not know that I knew naught, or that I lived or acted or desired."

The archeological evidence—which is indirect at best—suggests that humanity acquired language 500,000 years ago, ac­cording to anthropologist Leslie C. Aiello at the University of London.

The fossil clues of primordial throats and jaws suggest that humanity's distinctive anatomical capacity for speech may have evolved some 2 million years ago.

Language is a music played on the flute of the human voice, with a scale composed of more than 200 possible vowel sounds and about 600 possible consonants. Yet no language of the more than 6,500 estimated to exist today makes use of more than a fraction of those sounds to make audible the infinite permutations of thought, said UCLA lin­guist Peter Ladefoged.

To help tease the meaning from cas­cades of conversation, brain cells react in­stantly in unique patterns to the telltale sounds of speech—the pitch of a voice, the emphatic pause, or the rise and fall of a word, researchers at the Max Planck Insti­tute discovered earlier this year.

So precise is this vocal instrument that it makes only one sound error per million sounds and one word error per million words, Harvard University researchers say.

Fashioning a Grid With Crucial Importance

"Paul, can you open your eyes?"

UCLA neuropsychologist Susan Bookheimer is crouched under the pale blue tent of sterile, surgical drapes that surrounds Sailer's open skull.

"You are in the operating room," she says. "You are waking up."

Sailer's eyelids flutter open.

During the early hours of the opera­tion, Sailer was kept unconscious so that he was spared the pain and shock when Rubino laid open a palm-size flap of his scalp and skull bone. The brain feels no pain.

For the most crucial phase of the opera­tion, however, Sailer must be awake enough to answer questions.

Across the surface of Sailer's exposed brain, Rubino systematically arranges 21 tiny numbered squares, like the grid of a crossword puzzle.

Using the grid as a guide, the surgeon probes Sailer's brain for the invisible bor­der between the tumor and the cells that embody the young electrical engineer's ability to form words.

While every brain has overall anatomi­cal features in common, each is as unique as a fingerprint in its functional structure. The location of language functions can vary from one person to the next by 3 to 4 centimeters or more.

Complicating Rubino's task is the fluid geography of the brain. From the moment they were released from the confines of the skull, the neural tissues have been in flux:

swelling and contracting in response to breathing, blood pressure, fluid imbal­ances, the effects of anesthesia, and to the act of surgery.

Within minutes, the organ before him bears only a passing resemblance to the brain so carefully documented in high-resolution MRI scans and functional im­ages prior to surgery.

With a nod to the dozen neurologists, nurses and researchers crowding the room, Rubino generates an electric current to temporarily jam the neural network that allows Sailer to connect a word to the con­cept it labels.

Simultaneously, Bookheimer holds up a flashcard inches from Sailer's eyes. There is a line drawing of a reptile on the card.

As long as the current jams the neural activity of those special cells, Sailer cannot find the word for the outline of the familiar lizard-like beast.

He recognizes the creature, yet he just can't quite put a name to it. He stutters.

The current stops. The word—"alliga­tor"—abruptly comes to his mind.

Rubino is using his probe to trace the or­ganic outline of a mental ability.

In doing so, he is conducting a dialogue directly with the cells of the brain that ani­mate Sailer's mind; Bookheimer in turn is questioning the mind that inhabits the brain, using her word tests to discover where it is impaired.

So it goes for hours under the operating room lights: Probe. Flashcard. Question.

By trial and error, Rubino and Bookhei­mer navigate the wilderness of Sailer's brain a few cells at a time: It shines in the

sky. "The sun." Big orange vegetable. "Carrot." Color of grass. "Green." Animal giving milk. "Cow."

Again, Rubino touches a cluster of neu­ral cells with the electric probe to jam the neural signal.

Bookheimer holds up a picture of a park bench. "And this is called?" she asks. Sailer cannot find the word for it.

"You sit on it," she says. "A sheet?" "No," she says. The current stops. "A bench."

Five hours into the operation, the surgi­cal team has pieced together its map of the j place language holds in Sailer's mind.

To their dismay, the tests reveal that the tumor has infiltrated the critical naming area so deeply that they cannot discern re­liably where one stops and the other be­gins.

There is just one safe way to proceed, Rubino and Bookheimer decide: Only Sailer can guide the surgeon's hand.

They must keep Sailer talking while the surgeon removes the diseased tissue. When Sailer begins to stutter and stum­ble in his speech, as he did when the elec­tric probe was applied, Rubino will know he has removed as much tissue as he dares.

As Sailer continues to answer Bookhei-mer's questions, Rubino begins to suction away parts of the young man's brain.

"I am feeling things spinning around," Sailer says. "Spinning, spinning, spinning."

Academic Disputes Over Origins

Although communication evolved to bridge the gap between individuals, the end result for humankind is communal confusion.

If—as many scientists believe—humans have a universal instinct for language em­bedded in the biology of the brain, why did evolution come up with a system of com­munication that leaves so many members of the human family Unable to understand each other?

According to Genesis, God cicated Earth's many languages to confound those who had grown too powerful by speaking a single tongue. latiku, the mother goddess of the Acoma tribe of New Mexico, caused people to speak dif­ferent languages so that it would not be so easy for them to quarrel.

Today there still may be no more fierce scientific debate than the academic war

among linguists, neuroscientists, lan­guage theorists, neural network experts and psychologists over how this three pounds of fragile brain tissue—billions of cells woven together by the moist threads of neural synapses—can create the infinite variations of human commu­nication.

Noam Chomsky, the influential MIT language theorist, first proposed in the 1960s that people are born with an innate sense of grammar that transcends indi­vidual languages. Despite the dramatic diversity of languages, they all are cast from the same mold—a master plan rooted in human biology and shaped by a shared genetic inheritance—many lin­guists argue.

For Chomsky and his colleagues, this not only explains why languages have so many underlying elements in common but also why children can learn language with such astonishing rapidity and ease.

Recently, Guglielrno Cinque at the Uni­versity of Venice in Italy and his col­leagues surveyed 500 languages and found 40 core characteristics common to all of them that comprise a kind of periodic table of linguistic elements, from which all the variations of human language can be cre­ated.

In their view, sentences in every lan­guage are bawd'on a verb phrase sur­rounded by modifiers in predictable pat­terns. Certain adverbs such as "always" and "completely" in the same order whether a person is speaking Italian, Chinese or Serbo-Croatian, to name one such pattern.

"We are discovering that all languages really are identical, except in small fea­tures, which can combine in ways that re­sult in what look like vastly different lan­guages," said Rutgers University linguist Mark C. Baker.

Until recently, almost everything that was known about the human capacity for language was discovered through the study of the spoken word.

"Words and verbs are windows into the brain," said cognitive neuroscientist Steven Pinker at the Massachusetts Institute of Technology.

Now, however, there are hints of genes that can drastically affect language abil­ities.

Oxford University researchers last year found a gene on chromosome seven that appears to warp virtually every as­pect of grammar and language—so much . .-.so that the speech of the family that Inherited it is incomprehensible to an un­trained listener.

At Salk, Beluggi and her colleagues have shown that the deletion of a single copy of 20 genes on the same chromo­some can have almost the opposite ef­fect: an unusually fluent command of languages in a rare condition called Wil­liams syndrome, which is accompanied by mild retardation.

Certainly, heredity plays a key role in human language, experts agree.

But innovative studies employing new imaging techniques, such as PET scans, functional MRI devices and MEEG elec­tronic monitoring techniques, which can picture patterns of neural activity directly, are reshaping theories of how the brain speaks its mind. Computerized neural net­work experiments are also revamping con­ventional ideas of how language makes it­self at home in the brain.

Researchers at the National Institute of Mental Health have found that words fall­ing into broad categories, such as tools and animals, are stored in separate networks of neural connections. Other neural systems appear to handle words about colors and actions.

Men and women process language dif­ferently, brain imaging studies show. At Yale University, researchers Bennett and Sally Shaywitz found that language activ­ity was concentrated in the brain's left hemisphere among men but occurred across both hemispheres in women.

People who are bilingual appear to store knowledge of their native language differently than their second language,

depending on how old they were when they mastered the two ton­gues.

Nor is language or­ganized in babies' brains the way it ap­pears in fully formed adult brains, said Elizabeth Bates, di­rector of the Center for Research in Lan­guage at UC San Di­ego. That is because the experience of lan­guage itself helps cre­ate the shape and structure of the ma­ture brain.

Words alter the way the brain func­tions, researchers at Carnegie Mellon Uni­versity reported last month.

In an experiment that shows the impor­tance of culture and language training, re­searchers compared how Italian and English speakers read. They discovered that people used their brains to process words differently depending on their native lan­guage, although the words are written in the same alphabet. Students whose native language was Italian read faster and more easily than English speakers, no matter what language they were reading. And medical PET scans showed that they used different areas of their brains to do it.

That shows the powerful effect of lan­guage learning on neural pathways, the re­searchers said.

A Jumbled Conversation

Four days after surgery, Sailer is heavily medicated, but alert, energetic and talka­tive. He is up and walking.

To pass an idle half-hour, he easily as­sembles a 375-piece Lego model of a fanci­ful Star Wars vehicle.

But he cannot recall his wife's name without prompting, nor the names of those friends and co-workers who stop by to visit. He cannot remember the name of the college he attended or the name of the na­val division where he works.

Only the names of his mother and father spring easily to mind.

Sitting on the edge of his UCLA hospital bed, wearing a sky blue cycling cap to cover his incision, Sailer looks at his mother hesitantly and pronounces her name. "Sylvia."

As he spealcs, she silently mouths a dif­ferent word: "Mom."

He cannot read. His mind cannot yet re­solve the symbols on paper into any mean­ing. And his speech is sometimes garbled as his brain matches the wrong word to the concept his mind is trying to express.

"When he talks, he knows what he is saying although it is all jumbled," says Wendy Sailer, his wife. "If he just keeps talking, I end up figuring out what he is saying. It is clear his mind is working."

Such mental stumbles are a common side effect of brain surgery. Almost always they are temporary.

In the nine-hour operation, Rubino re­moved enough tumor tissue to leave a cav­ity in the left hemisphere of Sailer's brain about the length and width of the sur­geon's index finger.

Perhaps a fifth of the tumor remains in place, too intertwined with active language cells to be removed without irretrievably damaging Sailer's word formation abilities.

Even so, the surgery has renewed his lease on life, biopsy and medical scans show. The average survival rate with such a low-grade glioma growth is three to five years. The surgery may give him a decade or more.

But it may be several months before anyone knows how fully Sailer's brain will recover its abilities.

During that time, the state of his Eng­lish will be a crucial symptom of his mental recovery, especially as only the one lan­guage links his mind to the world around it. While his father was bilingual, having grown up in North Dakota in a German-speaking home, he did not pass the lan­guage on to his children.

Sailer does have a smattering of high school Spanish at his command. He also is fluent in the artificial languages of math­ematics and C++ computer code.

Now he gingerly fingers the stitches holding his skull in place and says he wishes he had studied Spanish harder so that today he would have a second lan­guage to replace any English skills he might have lost permanently.

He starts to stutter as he searches for the word for the concept he wants to ar­ticulate.

His wife supplies the word his mind can­not.

"Backup," she says. "You wish you had a second language as a backup in case this doesn't work out."

Sailer nods gratefully. "A backup," he echoes.

In each of a half-dozen cases at UCLA during the last year, patients who volun­teered for the experimental brain pro­cedure did so with the certainty that in their effort to hold on to life, they risked having to let go of something else—some portion of their ability to commu­nicate with the world around them.

For  58-year-old James Lasso from Las Vegas, his eight-hour operation was his sec­ond surgery to halt a malignant brain tumor growing in the crucial language   region known as Broca's area. For Paul Bingenhei-mer, 44, of Orange County it was the only way to end the epilep­tic seizures that had become too over­whelming to be con­trolled any longer by medication.

To 35-year-old com­puter consultant Pam­ela Stephenson of Lan­caster, it was a chance to correct a potentially deadly defect in a tiny brain artery located less than a centi­meter from neural cells critical to her abil­ity to read and comprehend speech. Her risk of stroke increased every year the de­fect in the artery was left uncorrected.

And for Sharon Neumann of Ventura the surgery was her third operation to con­trol a brain tumor that unchecked could kill her in months. Already, the tumor was destroying her ability to express herself.

"I do not have trouble understanding anything. I understand everything per­fectly," she says. awaiting her operation. "I can get. . . oh. . .I can get to the feeling ... to put the words together and I just can't do it.

"The big difficulty is putting my words together as they come. That seems to be my only difficulty. And my hands and my legs. It is that the ... oh ... when I get numb. . . and uh. . . um... I can't walk or write," she says.

Wendy Sailer spreads out 94 pictures of her husband's brain on the hospital bed.

The color images created by Bookheimer and her colleagues using an experi­mental functional magnetic resonance imager (fMRI) at the UCLA Brain Mapping Division depict how Sailer's brain func­tioned before surgery.

Together the husband and wife look at the pictures of the tumor that trans­formed their expectations of life to­gether.

They met during a singles' night at a Barnes & Noble bookstore in 1996. They got to know each other better by attend­ing a six-week lecture series on the Channel Islands. He took her hiking; she took him snorkeling. He proposed on his knees. They married two years later in a Methodist Church and honeymooned in Maui.

They were talking about starting a family when he had a seizure at work.

The brain surgery took place four weeks later. A second brain operation may be necessary in several years.

And as communication is the lifeline of any relationship, the challenge of this recovery also is the test of a new mar­riage.

"There are times I just sit in the back room and cry," Wendy Sailer says. "I didn't marry him to be with him a year, but to raise a family and to be together the rest of our lives.

"I am smart enough to know if I started thinking too much about that, I would not be there for what he needed," she says.

"I grew up in a family where we all talk way too fast and we all finish each other's sentences. He does not have to use a lot of words for me to understand what he is try­ing to say. There are a lot of ways of com­municating other than actually talking."

Benefits of Exercise

As the weeks pass, Sailer's brain regains much of its focus.

Names come more easily. His arithmetic skills are intact. He is becoming adept at navigating around the remaining blanks in his ability to express himself.

In his living room, Sailer sits on his custom mountain bike and energeti­cally pumps the pedals. It is mounted on a stand to keep the blue frame mo­tionless and steady as its narrow tires spin.

Even before his stitches are removed, Sailer is eager to be out on the bike paths. As soon as he has medical permission, he cycles up to a local mountaintop to watch the sunset.

— His enthusiasm for cycling may be aid­ing his mental recovery. Several new studies suggest that physical exercise triggers chemical changes in the brain that spur learning, at least in mice, by boosting the number of brain cells in the hippocampus, the part of the brain known to be centrally important in learn­ing and memory.

"I am getting more able to speak," Sailer says. "I still have trouble with some words.

"Vegetables. Throw me a picture of a vegetable and I block," Sailer says. "I keep going through all the names and I can't find the right one. The other day I bought some . . . red peppers ... at Costco and I came home and I said I bought some black things, some red things, green things.

"Even when I do say the word it doesn't sound right. I am trying to watch what I am saying and try not to say things I don't know and don't under­stand," Sailer says.

"When I try to describe something, I can still get bogged down on a item that I have a hard time with. So I describe things around it."

His peripheral vision is gone.

His reading ability has improved but it still can take him 10 minutes to finish a paragraph.

He is diagnosed as having dyslexia, ap­parently acquired as a byproduct of the tu­mor removal.

The engineer so conversant with techni­cal manuals and arcane computer code struggles to read the children's Golden Book version of "Winnie the Pooh."

"I am finding my 'Winnie the Pooh' is harder than my technical journals at work, but I may be imagining that," Sailer says. "The technical stuff may be harder but feels easier, even though it has large and complicated words. Maybe it is my feel­ings."

He has started weekly speech therapy. There have been follow-ups with his neurosurgeon and his neurologist, new MRI scans, new prescriptions and tests.

During a follow-up clinic visit at UCLA, Susan Bookheimer suggests that he start taking computerized lessons de­signed for children with reading disabil­ities.

Through weeks of exercises, the program retunes the brain by heightening its ability to distinguish subtle distinctions in sound that underlie how the brain proc­esses written words.

Bookheimer believes that portions of Sailer's intact right hemisphere can be coaxed into taking over from the cells that were removed during surgery.

"We suspect the white [neural] matter where your tumor was located was critical for transmitting this information," Book-

heimer said. "We are asking the remaining pathways in your right hemisphere to do something new."

Searching for the Right Word

With a deck of flashcards and a simple naming test, Susan Bookheimer draws out the mystery in Paul Sailer.

It is an enigma that the psychologist and the surgeon first glimpsed during Sailer's brain operation. To make it materialize now, Bookheimer shows Sailer a picture of a rooster.

"That is a cockle-doodle-do," Sailer says.

Turning over the next card, Bookheimer shows him a drawing of a duck. She asks him to name it.

"Quack. Quack. .Quack." Sailer says. He uses the sound like a trail of clues to locate the word in his mind. "That's a duck."

A giraffe. "It is sleeping."

A sea horse. "It is in the ocean. It is not a starfish."

A scorpion. "It walks and it stings peo­ple."

Each time, he recognizes the picture. His answers demonstrate he knows what he is looking at. Yet he cannot easily find the common noun that corresponds to the drawing.

The next picture is a mouse.

Sailer looks thoughtfully at the drawing. It is the second time in the space of a few minutes Bookheimer has shown him the same card, yet the name of the creature eludes him again. There is a pause.

"Squeak. Squeak. Squeak. Mouse." Sailer frowns. "I am frustrated," he says, "I know I have seen these pictures before."

By the end of the tests, Bookheimer has sorted the cards on the coffee table in stacks of hits and misses.

In all, Sailer misidentified 22 pictures of living things such as animals, fruits and vegetables, and identified nine cor­rectly. Shown pictures of nonliving things, he identified 30 correctly and missed seven.

He can name easily any man-made or nonliving object, but not entire animals or vegetables. He can name parts of animals without hesitation.

Yet his vocabulary is intact. He can use verbs fluently. He also can command com­plex grammar and syntax. There is nothing wrong with his memory or intellect.

In Sailer's mind, a single strand of the intangible web woven by language has been severed.

Indirectly, Bookheimer has limned the edge of the scar in Sailer's brain. It de­limits the physical border of a mental frontier that the three of them—patient, psychologist and surgeon—have crossed

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