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http://www.exploratorium.edu/exploring/bodies_mag/fmri_1.html fMRI: watching the brain at work by Jennifer Robins

exploratorium magazine online, vol 23, number 3

Your body is ... made up only of atoms, ... You are nothing else. So why do you feel more?

Well, because you feel at all, for one thing. And how, exactly, you manage to do that has stumped philosophers and scientists alike for centuries. The brain is the physiological final frontier. Because the function of its parts can't be guessed at by taking them apart, understanding how this enigmatic organ becomes so much more than the sum of them has been almost impossible.

With the advent of fMRI, though, that's begun to change.

Short for "functional magnetic resonance imaging," fMRI allows researchers to look at events instead of just structures, and does so with a great degree of precision. Color changes on fMRI scans show researchers which part of the brain is active when a subject performs a mental task such as speaking, listening to a bell ring, or solving a math problem.

"It adds function to structure," explains Dr. Joy Hirsch, Director of the Laboratory of Functional MRI at the Memorial Sloan-Kettering Cancer Center. "We've had a good grasp of the basic structure of the brain for twenty years or so—CT scans and X rays have provided that view. But fMRI noninvasively adds function: not just what it looks like, but how it works."

"These days it's pretty rare to identify new parts of the body," says Dr. Nancy Kanwisher, an MIT neuroscientist specializing in fMRI. "But in the last few years people have discovered dozens of pieces of the mind that no one knew about before. And finding pieces of the mind is more of a rush than finding pieces of the body ever could be."

Identifying those pieces has led to an explosion of information about how the brain is organized—and knowing the organizational plan is critical to understanding how any system works. Traditionally, physiologists have prospered from the mantra "form follows function." That is, natural selection forces a structure to evolve toward the most efficient design for its particular task. So by studying the design, we can make good guesses about the task.

For instance, if you'd never seen a typewriter before and wanted to figure out how it worked, you'd only have to take it apart. Likewise, draw a blueprint of the digestive tract and you've come a long way toward understanding how the body processes food. But take the brain apart and all you'll get is a mosaic of gray and white tissue—anatomy without obvious purpose. It's a black box instead of a machine; a computer instead of a typewriter.

Like a computer, the brain relies on electronic circuitry to perform its job. It stores data in both short-term and long-term memory. It rapidly sorts and processes information. Like a computer, you can't tell what it does by taking it apart; instead, you have to turn it on. But if it's on, you can't take it apart. Catch 22.

Functional MRI lets us look at what's happening inside the box while it's turned on. With it, we can see exactly what regions of the brain are activated when a specific task is performed, effectively getting form from function. The black box is growing transparent—and its design isn't what we expected.

For example, Kanwisher, who studies how we see things, has demonstrated that one region of the visual cortex is activated when a person is shown a picture of a place, but that a completely different region of the cortex is activated when a person is shown a picture of a face.

"Facial recognition is separated from other things in the visual system," she says. "We are extremely visual organisms. Over a dozen specific regions have been found in the visual cortex alone in the last few years, and more are expected."

Why would our brain use different neurons to recognize faces versus recognizing a familiar building?

"We're extremely social primates," Kanwisher says. "In the evolution of our primate ancestors, it was probably pretty important to survival to know who you were looking at; whether someone was a friend or a foe. It's also possible that facial recognition is simply very different from every other visual task and needs a highly specialized area. Or maybe we just look at faces so much more than anything else that the brain has specialized itself."

HOW MAGNETIC RESONANCE IMAGING WORKS

Functional MRI is a new technique involving MRI technology. You've probably seen MRI chambers on TV. The machine surrounds the patient, who lies still on a pallet inside a narrow cavern. A powerful electromagnetic field, considered to be harmless, is generated around the person. The electromagnetic field causes the nuclei of the body's hydrogen atoms (each a single, positively-charged proton) to stop their random spinning and align like compass needles. Precise radio waves are then slammed into the flipped nuclei, making the nuclei snap back to their original configurations. As they do this, they release energy in the form of radio waves that, echo-like, can be picked up by a detector and sorted out by a computer. Regions dense with hydrogen atoms will emit more radio waves, allowing the computer to generate a high-resolution, three-dimensional density map of the body.

Functional MRI adds another dimension to this. When neurons (nerve cells) are active, their metabolism increases significantly, requiring increased blood flow to supply oxygen and carry away metabolic waste. Blood that's carrying oxygen to the neurons has different magnetic properties than deoxygenated blood; as oxygen is rushed to active neurons, it causes a temporary increase in MRI signal that a computer can detect and amplify, giving a four-dimensional map in time and space of brain activity.

This is in contrast to previous brain-imaging techniques such as X rays and CT scans, basically three-dimensional X-ray images, good for looking at soft tissue structures like the brain, but yielding little functional information.

Electroencephalograms (EEGs), recordings of the brain's electrical signals made by attaching electrodes to the scalp, have helped researchers identify large, generalized regions of the brain, such as the temporal lobe and visual cortex. But the sensitivity of an EEG is limited to synchronous firing in large groups of neurons, and it has poor depth resolution—since the electrodes can only be stuck to the scalp, it's difficult to tell how far down an activity is located.

Positron emission tomography (PET) scans can perform a function similar to fMRI by monitoring increased sugar metabolism. Active cells use more of the simple sugar glucose than resting cells do. If glucose is radioactively "tagged," and then injected into the subject, its path through the body can be observed. But subjects are generally reluctant to be injected with radioactive material, even at very low levels. In contrast, fMRI is completely noninvasive.

As fMRI permits us to witness brain activity, the barrier between subjective and objective knowledge is beginning to shift. 

"There are elements of human experience that we all know are there, but we haven't been able to measure," says Dr. John Gabrieli, a Stanford neuroscientist. "But that doesn't mean they're not real. For every psychological thing you can think of, I believe you can find a correlative function in the brain if you measure it right."

In one novel experiment carried out in Kanwisher's lab, graduate student Frank Tong asked subjects to wear glasses that showed a different image to each eye. One eye saw a picture of a face, and the other a picture of a place. Because of a widely studied phenomenon called "binocular rivalry," the brain will only process one of these pictures at a time, but it randomly switches back and forth from one to another. Anyone who's looked at ambiguous figures such as "Old Woman or Young Woman?" may have experienced a similar phenomenon.

While the MRI machine recorded brain activity, the subjects in Tong's study pressed a button to indicate when the image switched for them. The active regions of the brain switched at the same time, physiologically verifying a phenomenon only the subjects could experience.

The benefits of viewing the brain this way—of translating the subjective into the objective—are potentially enormous to many fields. In education, for example, most decisions about methodology are based on behavioral outcomes. Reading instruction is a case in point. According to standardized tests, some children do better when they are taught phonics, learning to sound out letters and letter groups. Other students do better when they are taught to recognize individual words, seeing "dog" as a word, instead of sounding out "duh-aw-guh." This makes sense, because one person's brain can be very different from another's, stronger and weaker in different areas. Currently, the only way to tell how a child learns best is to wait a year or more to see if he or she falls behind at learning something one way, and then try to teach it another way.

What if we had a better way than standardized tests (which are really just behavioral output) to measure learning? Gabrieli and his colleagues have begun using fMRI technology to study how we learn reading skills. During the experiment, adult subjects are given mirror-reversed text to read. They read it very slowly, laboriously, often confusing "b" and "d," or "p" and "q." At first, their right parietal cortex, the brain region associated with spatial processing, is very active. After they've had a couple of weeks to practice, they return to the machine and can read better, though still laboriously. But now, their left temporal cortex, the classic language cortex, is active, just as it would be if they were reading normally. With further experimentation, researchers may get a good idea of what learning "looks" like, enabling them to measure it in children far earlier than standardized tests allow.

In observing traces of actual thought processes, we're learning that the brain is much more complicated than any computer we've ever encountered, even those designed to perform many tasks at the same time. 

"There's a level on which the brain must have algorithms to figure things out, like computers do," says Gabrieli. "And it must have input and output. But the brain is capable of massive parallel processing on a very high level. Some computers can do that, but not nearly on the same scale as the brain does." And the computer analogy, while useful, ultimately breaks down: almost every brain cell is its own processor, yet no cell can operate independently as a computer chip can, relying instead on neural networks. To an engineer, this may seem like an odd design, but there can be no question that the brain gets the job done very efficiently.

By mapping out functions within the brain and finding out how they overlap, we may begin to understand what mechanisms it uses to break apart tasks. We start to see how our brain transforms us from a metabolic, mobile "machine" into a person, complete with consciousness, creativity, and the ability to learn.

This kind of technology could also help us diagnose mental disorders and abnormalities, paving the way for better medical treatments. Gabrieli's lab has shown that children with attention-deficit/hyperactivity disorder (ADHD), a condition in which people are physically restless, have difficulty controlling their impulses, or have difficulty paying attention, show different fMRI activation patterns from children without the disorder. In one of the tests, young boys were asked to press a button whenever any letter appeared on the screen in front of them except the letter X. ADHD kids had trouble suppressing the impulse to press the button and didn't show increased activity in the regions of the brain that help regulate how we pay attention. Ritalin, the drug commonly prescribed for these children, increased ADHD kids' performance in the test and increased activation in those regions.

"It doesn't matter whether you're looking at a drug's effects or a learning process. By looking at the 'before' and 'after' conditions, we can watch the brain adapt its organization based on new functions," Hirsch says. She and her colleagues are using fMRI to uncover imaging criteria for what makes a good drug for the treatment of chronic pain. By mapping the brains of patients experiencing pain before and after the administration of various drugs, they learn better what to aim for in the development of new pain medication.

Neurosurgeons are also turning to fMRI to help remove previously inoperable brain tumors. Since tumors can often push other structures out of place in the brain, surgeons often will not risk removal for fear of damaging a nearby motor or sensory cortex because they don't know its new boundaries. Surgery might create a worse problem than the risk presented by the tumor.

But by using fMRI, Hirsch's lab has vastly decreased that risk. A patient can be scanned before surgery, mapping every standard function to create an individually-tailored image of the functional organization of that patient's brain. "Neurosurgical planning gives the surgeon a high-resolution roadmap so the operation can be tailored to the individual tumor," she says. The technique has facilitated the successful removal of tumors from over two hundred people.

Over the next decade, as the images become sharper and the black box more transparent, many more people will benefit. Likewise, our understanding of what makes us more than a collection of atoms will improve. Scientists are finally analyzing the brain, not by taking it apart, but by watching it at work.