For 18 agonizing months Ed Flynn talked to his comatose wife and stroked her skin, never knowing for sure if she heard him or knew he was there.
No neurologist or other expert could tell him. If only there had been some way to look inside her brain to see if there was any spark of
recognition, perhaps a tiny electrical signal that still carried some trace of the love and memories they once shared.
Why wasn`t there a machine to do that, he thought, to give him some hope that she still might recover or at least to show that her brain, the thing that made her uniquely her, had shut down for good and that the nightmare could be drawn to an end?
Out of that helpless desperation, Flynn, a physicist at Los Alamos National Laboratory in New Mexico, vowed after his wife died in May, 1980, to devote his expertise to developing just such a machine.
And now he has his chance. Flynn is hard at work on MEG
(magnetoencephalogr aphy), an extraordinary new way of looking inside the brain to see if information from the outside world is being received and if thoughts are being generated.
”One of the things we hope to look at is coma,” said Flynn, who added that the first experiments to determine if some coma patients can hear are expected to begin soon at the Albuquerque Veterans Administration Hospital.
”We now have a technique to see how far information is getting into the brain.”
Until recently all of science shared the frustration Flynn had felt as his wife lay in the coma. Protected by the skull, the hardest bone in the body, and a blood-brain barrier that prevents unwanted chemicals from reaching it, the brain has until recently defied all attempts to look inside it in ways that did not damage its delicate fabric.
The only ways scientists could study the brain were to measure its diffuse electrical activity or to dissect it in an autopsy, and then the organ revealed little or no information about how it worked when it was alive. The brain was the body`s black box.
That started to change in the 1970s, when scientists began developing a series of marvelous machines that for the first time allowed them to peer inside the living human brain. The new imaging machines are a key part of the revolution in brain research during the last 10 years that is drastically accelerating man`s understanding of the brain.
What they saw was astonishing. Not only could they view the structure of the brain in exquisite detail, but they could see its function, its living chemistry. They could see neurotransmitters, the brain`s chemical messengers, in action. They could see where the neurotransmitters delivered their messages.
Unbelievably, they were looking at the brain thinking.
Like other technologies that have opened up previously unseen worlds, scientists hope the new imaging machines will do for brain research what giant telescopes did for astronomy in revealing a breathtaking view of the universe and what microscopes did for biology in exploring the ultrasmall realm of cells, microbes and molecules.
”The new imaging techniques are wonderful because they essentially turn the brain to glass so we can look inside and see what`s going on,” said Dr. Jerre Levy, a University of Chicago biopsychologist.
This unprecedented view is expected to lead to methods for diagnosing mental disorders, predicting behavior and personality, evaluating mental capacities and basically determining when a brain is working well and when it is not.
”It`ll be like taking your car in for an electronic diagnosis to see what`s wrong with the wiring,” said Dr. Floyd E. Bloom, chief of the division of preclinical neuroscience and endocrinology at the Research Institute of Scripps Clinic in La Jolla, Calif.
”Someday you`ll be able to be hooked up to an imaging machine and have a diagnostic workup that tells you whether your brain is responding as normal ones do . . . or as the brains of people . . . with mental illnesses,” he said.
Computerized tomography (CT) was the first of the imaging devices. It uses low-dose X-rays and sophisticated computers to make an image of a slice of the brain. Even better images came from the next technique, magnetic resonance imaging (MRI). It uses powerful magnets to tune in to tiny radio signals given off by the molecules that make up brain tissue, thereby providing their exact location.
Both produce accurate images of the internal structure of the brains in living people that were previously obtainable only postmortem.
Then came SPECT (single photon emission computerized tomography) and PET
(positron emission tomography), which use radioactive tracers to measure the brain`s metabolic function as it processes information. Tracers are made up of sugar or oxygen, which have been tagged with a radioactive molecule to tell the imaging sensors where they are in the brain. Because brain cells increase their consumption of sugar and oxygen as they become more active, the radioactively tagged compounds allow researchers to measure which parts of the brain are actively processing information. PET, the more powerful of the two, tracks the chemical residue of thoughts.
MEG (magnetoencephalography) is the latest mental Peeping Tom. Some scientists believe it may eventually be the best because it can detect thoughts as they occur, making it faster and potentially more accurate than PET or SPECT.
The brain is an electrochemical organ. When excited, a brain cell, or neuron, fires an internal electrical charge. Each cell plays a role in the brain`s vast communication system. When a brain cell fires, that is a signal for sending its message to other neurons. It does so by releasing chemical transmitters. A second neuron takes up the transmitters and then decides whether to crack its own electrical whip and send chemical messengers charging on to other brain cells. Neurons fire at the rate of 50 to 600 impulses per second, depending on what they are doing and how busy they are.
Unlike PET or MRI, MEG does not use radioactive tracers or X-rays. With supersensitive equipment, it measures the fantastically small magnetic fields in the brain that accompany the electrical activity generated when cells orchestrate the movement of a finger, the recognition of a face or the solution of a math problem. The brain`s magnetic fields are a billion times weaker than the Earth`s magnetic field and a million times less than the magnetic field in a metal door.
Even the EEG (electroencephalogram) is being resuscitated. EEG, which measures brain electrical activity, has been around for nearly 75 years, and for most of that time it was the only means of getting any kind of information out of the living brain. That information was limited, however, because the electrical activity produced too many confusing signals and it was hard to figure out what they meant. For example, an EEG might show that a coma patient was alive but not whether any recognition or sensory activity was occurring.
But with refined equipment and new computer programs, the EEG is beginning to sort out different electrical patterns associated with mental disorders. Within the last two years EEG programs have become commercially available to help psychiatrists diagnose schizophrenia, depression and other problems.
The machines augur profound changes. For one thing, they will dramatically alter the way psychiatrists make diagnoses. Trying to figure out what is wrong in a person`s head has been limited to the symptoms described by the patient, an indirect and often misleading path to the brain.
”We as people are very poor at being introspective in a biologically accurate way,” Bloom said. ”We can say, `I feel nervous,` but we can`t say, `I feel nervous because my hippocampus (involved in long-term memory) is discharging 12 times more frequently per minute than someone else`s.`
”That kind of information will be available to us. We`ll be able to be very precise, mechanical and quantitative about the differences between our own brains at different times and between other brains under similar conditions. That kind of information will be totally useful in predicting what`s wrong in mental illness,” he said.
But that kind of information is also a double-edged sword. The ability to evaluate brains-to measure the learning capacities of children, to diagnose mental disorders, to detect deteriorating brain function in executives or pilots-could be a blessing or a tragedy.
”Almost any technology has some potential for bad as well as good,”
said Dr. E. Roy John, director of New York University Medical Center`s Brain Research Laboratory. ”Whether its potential is developed for good or bad is really decisively controlled by the society that uses it.”
If, for instance, the technology is used to label children according to their mental capabilities, that could be terribly harmful. If, on the other hand, it is used to identify a child`s strengths and weaknesses so that he can be helped to realize his potential, then it could be wonderful.
The ability to evaluate brains is already here, John said. After 15 years of research, John developed the Brain State Analyzer, a computerized program that uses EEG recordings to diagnose learning disabilities and a variety of mental disorders.
The device, which is being marketed by Cadwell Laboratories of Kennewick, Wash., color-codes brain waves. Schizophrenia, depression, manic-depressive disease, alcoholism, dementia and other disorders show up as characteristic patterns. Red indicates abnormally high electrical activity in certain areas of the brain and blue too little.
”We can see pictures of brain abnormalities that correspond to the diagnoses that, until now, psychiatrists have been making on the basis of the words of the patients,” he said. ”It shows you the physiological basis of mental illness.”
Patients suffering from depression and manic-depression, different disorders, often go into a psychiatrist`s office complaining of the same symptoms. It`s hard to tell them apart based on their complaints, but the Brain State Analyzer can make the correct diagnosis 94 percent of the time, John said.
The most surprising finding is that the brains of normal people all over the world may have more in common than anyone ever thought.
Studies conducted with thousands of normal people in eight countries showed that they had similar EEG patterns. These patterns fluctuated in the same way among all groups as their EEGs changed during their lifetimes.
”We have found that the brain follows electrical rules that change in a lawful way from childhood to old age,” he said. ”Healthy people have a pattern of electrical activity that is very accurately predicted by those rules, and it doesn`t depend on their racial background or their cultural background.”
The Brain State Analyzer may also improve treatment because it can detect the effects of drugs or other therapies in normalizing brain waves even before patients notice any improvement, John said.
Although the analyzer is the first imaging device to become commercially available to aid doctors in diagnosing mental problems, some of the other techniques ultimately are expected to be more powerful.
Whereas EEG signals provide a view of diffuse brain activity, MEG measures cell function at exact locations in the brain. It can, for example, tell the different parts of the brain that become active when a finger or a thumb is moved.
MEG also can distinguish the area of the brain where the thought of moving a finger originated, which is a few centimeters away from the area that actually orders the finger to move.
The U.S. Army already is interested in the technique`s potential for picking people for specialized tasks, based on how their brains work. Some people make better pilots because they have faster reflexes, while others may be better tank drivers because their peripheral vision is sharper, skills that the brain oversees.
”We`re working on programs now for the Army to see if we can develop a screening procedure for troops to see if we can say here`s the best guy for the right job,” said Flynn, chief of the neuromagnetism team at Los Alamos National Laboratory.
Finding out what in the brain makes some people better at certain things than others will have wide implications.
”It`s not going to happen next year, but down the road we hope that we can pick out prospective geniuses in certain areas, or at least people with very useful capabilities, and put them in the right jobs,” he said.
”It would be useful for the individuals themselves, if they are willing to accept that, as long as it`s not forced on them.”
While MEG is still in its infancy, PET is beginning to take its first shaky steps. Dr. Louis Sokoloff of the National Institute of Mental Health was the first to discover a way to make the brain identify its thought processes. He used glucose, or sugar, the brain`s fuel. The more active a brain cell is, the more it gobbles up glucose. He attached a radioactive molecule to glucose so that after the glucose is injected, sensors can follow it as it travels throught the brain. But even with a radioactive tag, glucose is burned up by cells too fast to leave much of a trace.
Sokoloff overcame this problem by making a special form of fuel called deoxyglucose that brain cells take in like glucose. The only difference is that deoxyglucose gets temporarily stuck in cells, allowing its radioactive beacon to identify neuronal activity.
Using Sokoloff`s technique, David Hubel and Torsten Wiesel made an amazing discovery. They found that specific parts of the visual cortex, the area of the brain at the back of the skull responsible for vision, processed certain kinds of information coming in from the eyes.
Their finding, for which they shared a Nobel Prize in 1981, supported the theory that the brain is made up of modules, that certain areas do certain things. It meant the brain could be mapped and that learning how these networks interconnected could lead to a better understanding of behavior.
Sensory information from your eyes, ears and skin, scientists now think, is broken down into signals that travel to the appropriate modular points in the top layer of the brain. That information then is transmitted to other places in the cortex, where it is interpreted and compared with other events in your recent and distant memory.
Ultimately other systems that deal with emotion and reward check out the data before a decision is made whether to ignore it, store it for long- or short-term memory or act on it immediately. A lot of the process is subconscious, like jerking your finger away from a hot stove. But brain cell activity increases and decreases at every step, and the radioactive beacons faithfully follow it.
These kinds of mental acitivities now can be seen with PET. Pioneered in the 1970s by Michael Ter-Pogossian, a Washington University physicist, the PET machine is just coming into its own as a sophisticated scanner of brain activity. The device detects radiation from positrons, subatomic particles emitted by radioactive tracers.
The University of Chicago`s Levy is using PET to study normal brains and is finding that brain metabolism is stable. People have the same PET images when they do the same task at different times.
Furthermore, images of brain function can be used to predict certain behaviors and possibly even personalities, Levy said.
Some people who make mistakes on a button-pushing test, for instance, will display a certain brain image. Levy can predict that other people with that same pattern will make the same mistakes 70 percent of the time.
In some people the brain`s right side is more active than the left; in others just the opposite. Still others have equal activity in both
hemispheres. Because the left brain is thought to be involved with language and art, the right brain with logic and nonverbal processes, lopsided activity may predispose people to certain types of personalities, Levy said.
”We have data indicating that these individual differences in the activation levels of the hemispheres are correlated with personality characteristics, cognitive abilities and things like that,” she said.
PET can also pinpoint receptors on brain cells where neurotransmitters attach to convey their messages. Tagged with radioactive beacons,
transmitters, or substances that mimic them, can be followed to specific cells where they lock in.
The receptor is important as the brain`s link to the outside world. It is also the weakest point in the brain; receptor malfunction is responsible for most mental disorders.
In 1973 three teams of scientists discovered the first receptor in animals, the opiate receptor. Because psychoactive drugs work at receptors, the goal of researchers is to develop new compounds for treating mental disorders that either block or enhance the activity of receptors.
The first human receptors examined with PET were lit up in the brain of Dr. Henry Wagner, director of Nuclear Medicine and Radiation Health at Johns Hopkins` School of Public Health. Using himself as a guinea pig, Wagner, in May, 1983, was injected with radioactive tracers that lit up his dopamine receptors. (Dopamine is an important neurotransmitter that is involved with such things as emotions and initiation of movement. Excess dopamine receptors in one part of the brain have been linked to schizophrenia.) About a year later he did the same thing to image his opiate receptors.
”To see the chemistry in your brain and to be able to relate it to your feelings really makes you realize that there are chemical reactions going on in your brain that affect your behavior,” Wagner said.
He and neuroscientists at other centers are using the new technology to learn how a person`s experiences affect transmitters and how these chemical messengers in turn affect feeling, thinking and behavior.
A person who is learning something nice or pleasant, for instance, may be rewarded with a squirt of enkephalins, one of the brain`s own opiate transmitters.
”When you present that idea to people, the first thing they say is that it sounds like a gross and bizarre oversimplification,” Wagner said. ”But it certainly affects your behavior.”
Scientists hope this path may lead them to understand such things as whether squirts of inappropriate transmitters cause aggression or violence. Are drug addicts, who use chemicals that plug into the brain`s opiate receptors, trying to make up for a lack of enkephalin rewards from an impoverished childhood?
Wagner`s group has found that dopamine receptors decline with age, especially in males. Is the decline of dopamine receptors what causes men to mellow as they get older? Could this explain what law enforcement officials have long observed, that adolescents who commit the most violent crimes lose their violent tendencies as they age?
PET scans have also revealed characteristic abnormal patterns in the brains of people with panic attacks and obsessive-compulsive disorders.
”Relating brain chemistry to mind function is an unbelievable ability,” Wagner said. ”We`ve had one view of the brain from above through psychology, sociology and linguistics. And we have a view of the brain from below with the study of molecules, synapses and membranes. Now the imaging devices allow us to join these two views.”
