Biomedicine

Your Brain on Booze

Scientists are using a new brain imaging technology to understand how chronic drinking damages wiring in the brain.

Knock back a few too many and you’re likely to wake up with a hammering headache. But that short-term hangover pales in comparison to the long-term effects of alcoholism. Chronic drinking can lead to cognitive problems, such as impaired memory and problem-solving, and brain damage.

Scientists have already uncovered some of the major structural differences in the brains of alcoholics using magnetic resonance imaging, which gives a picture of the size and shape of different structures on the brain. But, until recently, researchers had been unable to study the fine network of nerve fibers that carry information from one brain area to another. These fibers are crucial for maintaining proper processing speed in the brain, so disrupting this circuitry could lead to many of the cognitive problems associated with alcoholism.

Now a new technology, known as Diffusion Tensor Imaging (DTI), is allowing researchers to examine how alcohol affects this fine-scale wiring. DTI measures the diffusion of water molecules in the brain. In many brain areas, water molecules move around randomly. But nerve fibers (commonly known as “white matter”) are coated in a fatty substance, which forces water molecules to diffuse in the direction of the fiber. Scientists can construct a picture of the fiber tract by measuring the direction of diffusion. When water diffusion in a particular brain area is less organized than expected, scientists know there is a problem with the wiring in that area.

Edith Sullivan, a neuroscientist at Stanford, has spent the last 20 years studying how alcohol damages the brain. In the last few years, she’s added DTI to her arsenal of brain-imaging techniques. Using it, she found that alcoholics have suffered damage to specific parts of their corpus callosum, the thick tract of white-matter fibers connecting the two hemispheres of the brain. Sullivan and colleagues also found that these abnormalities are linked to problems in attention and working memory, a form of memory allows one to remember, say, a phone number long enough to dial it.

Fortunately, research from Sullivan and others has shown that some parts of the brain can bounce back with sobriety. Now, Sullivan and collaborator Adolf Pfefferbaum, also at Stanford, are running a study of 200 healthy people, recovering alcoholics, and recovering alcoholics with HIV, to determine if the white-matter fibers can also recover.

“The brain damage [associated with alcoholism] is accrued over years and it will probably take years for the brain to recover,” says Sullivan. “That means people have to be in some form of rehab for an extended period of time in order to recover and live a relatively normal life and perform at a pre-alcoholic level.”

Daniel Hommer, chief of the brain imaging lab at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, MD, says it’s not yet clear how big a role changes in white matter play in alcoholism, but that DTI will allow scientists to answer that question.

Some parts of the brain may be able to recover when adults stop drinking, but what happens to teenagers who begin drinking? White-matter circuits may be particularly vulnerable in them, because these fibers continue to develop during adolescence. Susan Tapert, a psychologist at the University of California in San Diego, is studying white-matter development in teenagers who use alcohol and marijuana. “Because white matter is so clearly affected in adult alcoholics, we wonder when in the course of heavy drinking these problems develop,” says Tapert. “And because there is so much white-matter growth during adolescence, we want to know what happens if you damage those fibers early on.”

Previous studies using structural MRI show hints of white matter abnormalities in alcoholic teenagers. Now Tapert will use DTI to better characterize these changes, and to see how the defects are linked to cognitive problems in teenagers who drink. Preliminary results suggest that wiring defects relate to poorer performance on many kinds of tests, such as verbal skills, planning, and organization. “The differences are relatively subtle – it would probably translate to the difference between an A and B in school performance,” says Tapert. “But that is still enough to impact the outcome.”

Alcohol can also affect white matter very early in development: when a baby is still in the womb. For example, in rare cases, children with fetal alcohol syndrome are missing a corpus callosum. Other children exposed to prenatal alcohol have more subtle problems with their white matter. Claire Coles, a psychiatrist at Emory University in Atlanta, GA, has followed a population of children with fetal alcohol exposure since birth. Coles and colleagues found that these people, now in their early twenties, have significant differences in their corpus callosa compared with controls. The white-matter defects correlate with a slower speed of processing, as well as overall IQ, she says.

Edward Riley, at psychologist at UC San Diego who’s starting up similar studies, says the research could help doctors to distinguish children who have learning disabilities linked to prenatal alcohol exposure from those who have learning disabilities from other causes.

“In mental health disorders such as alcoholism, we are not very sophisticated in terms of figuring out what is wrong with a particular person and how to help them,” says David Oslin, a psychiatrist at the University of Pennsylvania in Philadelphia. “Tools that help us understand subpopulations of patients and their neurophysiology are potentially very helpful. DTI may be a good way of determining that.”

Images on home page are DTI images of a brain with fetal alcohol syndrome. Colors in righthand image indicate the direction of fiber tracts in the brain. (Images courtesy of Xiaoping Hu, Department of Biomedical Engineering, Emory School of Medicine, Atlanta GA.)

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