Mind movies
Those patterns start out as brain scans taken with a magnetic resonance imaging machine, or MRI. With the MRI, it's as if the brain were an apple sliced into thousands of thin sheets. That's a decent start. But it's hard to get a complete picture of brain anatomy from any one slice. The hundred billion or so neurons that make up our minds form incredibly complex 3-D structures. These clusters of cells vary in thickness, wind around fluid-filled spaces, and are crossed by thousands of creases, canyons, and fissures. A thin cross-section eliminates much of this vital detail and makes it hard to compare whole features in one person's brain with whole features in another.
Thompson's solution was, essentially, to map this complex neurological landscape onto a grid. Like a topographical map of real-world canyons, these grids keep accurate information about the size and depth of brain canyons but gave them a common scale so they could be compared. Using that scale, infinitesimally small features from one brain can be laid on top of similar features from another brain, and size, shape, or thickness can be measured against one another. Do this for a few thousand brains, and you can get an average shape for any brain feature.
The next step is to compare this average brain with an unusual brain, one afflicted with a disease such as Alzheimer's. Because the Alzheimer's brain has lost cells, the two brains won't be the same. It takes a certain amount of bending or flexing to make the two shapes conform; the degree of that bending gives Thompson a measure of the changes wrought by Alzheimer's. He then can blow the brain back up into a lifelike shape, coloring the areas of greatest difference from normal.
Thompson has done this for Alzheimer's brains at first diagnosis, then repeated it every few months. The resulting maps reveal that gray matter loss starts in a region called the hippocampus, a memory area, and quickly moves to the limbic system, which is involved in emotions. Within 18 months, it hits areas in the brain's frontal lobes, which are used to control impulses and make decisions. This nicely tracks the sad sequence of behavior changes that psychiatrists--and family members--have long noted.
"Basically, we're getting a series of snapshots of the brain that show, in fine detail, which structures are getting hit by the disease and to what degree," says Thompson. "And what I think is exciting about this is that it presents us with targets for drugs. We can try a drug, or a combination of drugs, or even diet, and see if it slows down the rate of cell loss in these areas." Indeed, Thompson is now part of a large trial testing Aricept, a commonly used drug that appears to have moderate effects in the early stages of the disease, in combination with the antioxidant vitamin E. The vitamin has been evaluated already with memory tests, showing little effect, but the combination may be more potent. And if it is, that potency will show up in the brain maps.
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