THE LATEST AND GREATEST , IMAGING THE BRAIN

THE LATEST AND GREATEST(?): IMAGING THE BRAIN

It's hard to find a media story about the brain that doesn't refer to the lat­est technology for imaging the activity of the brain, most often using Functional Magnetic Resonance Imaging (fMRI). This is a powerful tool for imaging ongoing brain activity in humans as well as animals. As with structural MRI that yields "still" images of the brain, fMRI uses magnetic fields rather than radiation to image the tissue. So, as far as we know, there is no safety issue about long or repeated exposures (unless you have something in your body that can be magnetized).

fMRI depends on a particularly useful property of hemoglobin, the molecule in red blood cells that carries oxygen to all tissues, including those in the brain. As you may have learned in biology class, oxygen is bound to hemoglobin in the blood and is released from hemoglobin as blood perfuses tissues that need oxygen for producing energy The mag­netic properties of hemoglobin change as the hemoglobin releases oxygen to tissues. Thus, the fMRI system looks for changes in magnetic signals as

tissues consume oxygen. The signal is called the blood oxygen level dependent (BOLD) signal.

When neural circuits are active, blood flow increases in those areas and oxygen is stripped from hemoglobin in the blood. Thus the BOLD signal changes to reflect that shift in the amount of hemoglobin that has oxygen bound to it. So literally, one can lie in an fMRI machine and decide to wig­gle one's thumb and watch the brain activity associated with that move­ment. What you are really looking at is blood flow and oxygen-consumption changes in the brain areas that control that movement—not the electrical activity of the brain. The BOLD signal lags the neuronal activity for one to two seconds, and there is still controversy about what exactly triggers the

increased blood flow and oxygen delivery. But it is safe to say that fMRI is measuring brain activity.

fMRI has its limits. First, there is the time issue we just mentioned, because the signal lags the neural activity for a long time compared to the firing rate of neurons. Then there is the issue of spatial resolution. The very best fMR. I resolution (at this writing) is a cube that's about one milli­meter on each side—and that requires a machine with a very strong and expensive magnet. That one-millimeter cube contains many neurons and synapses between them. So, using an fMRI to examine brain circuits is a bit like looking at a low-resolution TV—there is information there, but not as much as one would like. Another problem is that it is not possible to determine whether a BOLD signal in a brain area is a result of that area transmitting information or receiving information. All we can say is that

the area is active. Furthermore, we don't know the result of that activity_

it may be stimulating or shutting down its neighbor by activating neurons

that normally slow down cells they contact.

Finally, the BOLD signals are very small compared to the background activity. This requires that the fiVIRI system average the images to reveal the relevant activity of an area. To further emphasize the active area, col­ors are used and the contrast is enhanced. Those techniques are very help­ful to scientists but can produce images that are misleading to nonscientists. One of us was consulted by a major television network talk show about the effects of ecstasy as shown by brain images (not fMRI, but it doesn't matter) of individuals who had used the drug. The images had very high contrast, and it appeared that the ecstasy users had "holes" in their brains. In fact, there was just a small percentage difference in the true signals, but the images had been enhanced to emphasize those differ­ences. Nevertheless, they talked about ecstasy producing holes in the brains of users.

fMRI has been used to monitor brain activity in a vast array of studies, ranging from epilepsy to lie detection. It has also been used to image the response of the brain to various drugs as scientists try and determine where in the brain a drug acts to produce a change in behavior. To some extent this works. For example, one can show pictures of cocaine to non­users and compare their response to the response of cocaine addicts. The BOLD images can vary remarkably between brain areas. But it is hard to know exactly what these changes mean.

First, individual variations make it hard to draw conclusions about a particular individual's responses. Doing studies with groups of people and averaging the group results produces reliable images, but we are not yet at the point of being able to image one individual and draw firm con­clusions. Second, even if a brain area is reliably activated in some circum­stance, we don't know enough about the brain to know exactly what each area does. Probably most important, brain activities are executed by coor­dinated signaling between a variety of areas, and fMRI may not be able to tell us the direction of signal flow or what role an area is playing. Finally, variations in signal strength may obscure proper interpretations. This could easily happen if a very small collection of neurons exerted powerful effects on a much larger circuit. The BOLD signal from the small number of neurons initiating the activity might not even be visible, while the larger circuit would dominate and appear to be the source of the activity

All of this is not to say that fMRI and other brain imaging tools should be ignored. They are truly fantastic tools to begin to understand the rela­tionship between behaviors and brain activities. As they become more refined, they may be able to reveal individual differences that have diag­nostic meaning. But our advice at this moment is to view the nonscientific media with a degree of caution and to not be seduced by pretty pictures.

WHY SHOULD ANYONE CARE ABOUT ALL OF THIS?

We hope that this chapter offers some good reasons to develop a respect for the brain and the body that supports it, as well as some insight into why drugs do what they do. This is especially important for teenagers, because as every teenager knows, they are different from adults.

What adults may not know is that the teenagers are right. For some time we have known that the very immature brain, as in babies, has a number of characteristics that are different from the adult brain. Now we are finding that the adolescent brain may be different also. It may respond differently to drugs, and it may learn differently.

A psychologist at Duke University, Dr. David Rubin, carried out a fasci­nating series of experiments showing just how different young people may be. The basic experiment was to take adults at various ages and ask them questions about events that occurred in every ten-year period of their lives, including a lot of trivia. Of course, recent events were remembered fairly well, but other than those, the events best recalled were those that occurred during young adulthood (from age eleven to age thirty). This means that a senior citizen recalled his life events and what was going on in the world during his adolescence even better than those events that had occurred just

a few years earlier.

If our conclusions from this research are correct, then there is some­thing very special about either our brain biochemistry or our psychologi­cal state during adolescence that enables us to store our experiences for life. Whatever the explanation, the implications are clear—the experi­ences, good or bad, that we have during our youth are very well stored in our "sober" memory systems and can be recalled for the rest of our lives. Thus, when teenagers say they are different, they are right, and when adults say that these are formative years, they, too, are right.