Using water and technology to map alcohol's effects on the brain

August 13, 2000

Most experts believe that the body is composed of about 95 percent water. Diffusion Tensor Imaging (DTI) is a Magnetic Resonance Imaging (MRI) method that is sensitive to the detection of water in the body. In a recent study in the August issue of Alcoholism: Clinical & Experimental Research, researchers use DTI to track the movement of water molecules in the brain in order to closely examine alcohol's effects on brain white matter.

"The brain is composed mainly of gray and white matter," explained Adolf Pfefferbaum, director of the Neuropsychiatry Program at SRI International and lead author of the study. "Gray matter represents neuronal cell bodies as well as other 'packing' material; about 80 percent of gray matter is water. White matter includes the long fibers extending from the cell bodies that serve as cables connecting different brain regions; about 70 percent of white matter is water." DTI is especially useful for tracking the movement of water molecules in brain regions with a 'regular structure,' he said, such as the cable systems of white matter.

Postmortem studies of animals and humans indicate that brain white matter is especially vulnerable to excessive alcohol consumption. However, it is not known for sure by what biological mechanisms white matter becomes disrupted. Some studies have suggested that alcohol toxicity may directly degrade white matter fibers. Others suggest that certain nutritional deficiencies (especially thiamine deficiency) that commonly occur with alcoholism are responsible for white matter destruction.

"This study examines the effects of chronic, excessive alcohol abuse on brain functions at a level previously unavailable for study," said Sara Jo Nixon, professor and co-director of the Oklahoma Center for Alcohol & Drug-Related Studies. "For years, we have been able to identify some of the changes in brain structure and general function associated with alcoholism. However, the current work significantly expands these findings. Specifically, it focuses on changes in the material (myelin or white matter) associated with the movement of neural messages down the neuron. Furthermore, it links these changes to alterations in cognitive processes such as attention and working memory."

"There are different types of white matter in the brain," Pfefferbaum said. "By and large, the function of white matter is to connect distant and not-so-distant brain regions. These white matter 'cables' are called axons. Axons can be very narrow and short, or thick and quite long. Long axons are typically covered with a sheath of myelin, which is a relatively fatty substance that promotes speed of information transmission, that is, cell-to-cell communication. This communication is especially fast when conducted through large, myelinated fibers, which is what you will find in healthy brains. What animal models of alcoholism and postmortem studies of alcoholics have revealed is a demyelination of the white matter tracts. DTI can help us identify this finely grained myelin degeneration in the living alcoholic."

"This study has enormous potential importance in two fundamental ways," noted Nixon. "First, using sophisticated technology that has heretofore not been used in alcohol studies, it demonstrates significant changes in brain white matter, which affects the efficiency with which messages are transmitted within the neuron. Thus, theoretically, changes in white matter might be associated with changes in brain function, even if brain lesions were not detected. However, and this leads to the second point, significant relations between previous, existing imaging data and performance have often been modest at best. This study suggests that the DTI approach for assessing white matter function may be a clearer indicator of functional impairment of attention and working memory processes." In other words, Nixon said, this study suggests that alcohol-related damage to brain white matter, independent of any loss of gray matter or neuronal cell bodies, may be linked to at least some of the neurocognitive deficits observed in detoxified chronic alcoholics.

Acknowledging that the intricacies of brain function are complicated, Pfefferbaum described some of the practical applications of his findings. "Identification of the microstructural condition of the brain's white matter may help us to understand the cognitive and motor deficits that many alcoholics suffer," he said. "This kind of research may also shed light on neural mechanisms that may be modifiable with long-term alcohol abstinence."

Given what Nixon called the "preliminary, yet provocative nature" of these findings, she called for additional studies, as well as for more attention to be paid to the effects of chronic alcohol intake on female neurocognitive performance.

Indeed, that is what Pfefferbaum proposes to do. "We are now examining white matter microstructural integrity in alcoholic women," he said. "We will also conduct longitudinal studies to examine how the long-term course of alcoholism affects white matter integrity."
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Edith V. Sullivan of the Department of Psychiatry and Behavioral Sciences at the Stanford University School of Medicine; Maj Hedehus, Elfar Adalsteinsson, and Michael Moseley of the Department of Radiology at the Stanford University School of Medicine; and Kelvin O. Lim of the Nathan Kline Institute for Psychiatric Research in Orangeburg, NY. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the Lucas Foundation.

Alcoholism: Clinical & Experimental Research

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