Using PET to Determine Alcohol's Effects on Brain Structure and Function

by National Institute of Health

(Page 2 of 6)

The Molecular Basis of Positron Emission Tomography (PET)

Positrons and electrons are some of the tiny particles that make up atoms. As the name implies, positrons carry a positive electrical charge whereas electrons carry a negative electrical charge. Positrons are contained within the nucleus of each atom and can be released from atoms during the decay of unstable, radioactive atoms or molecules. The positrons can then be detected by scanners with sensitive cameras.

Radioactive decay is the basis of PET technology. The radioactive compounds required for PET (also called radiotracers) are generated in a cyclotron - a sophisticated machine to damage the nuclei of chemicals. Directly after their synthesis, the PET radiotracers already begin to decay and release positrons in the process. (Because the radiotracers used for PET generally decay very rapidly, PET is an extremely expensive procedure available only at selected facilities with or near cyclotrons.) Small amounts of the radiotracer are injected into the subject's bloodstream, which distributes the tracer to the tissues, and the subject is placed in the PET scanner. During the radioactive decay of the radiotracer, the released positrons collide with electrons, resulting in the production of two particles of light (photons). Sensors within the PET scanner detect the photons, and attached computers with sophisticated software can use this information to identify the position of the original positrons. With the help of computed tomography obtained immediately before the PET, the computer can then generate three-dimensional images of the source of the photons. The computer also counts the collisions between positrons and electrons at each site in the brain, and these counts are proportional to the amount of radiotracer present at that site. For example, one can generate radiotracers that specifically bind to receptors for the neurotransmitters dopamine or serotonin. These radiotracers will bind to the receptors, with higher concentrations of the radiotracers accumulating in those brain regions that contain higher concentrations of the respective receptors. With this approach, investigators and clinicians can estimate the density and the distribution of particular neurotransmitter receptors in the living human brain. Currently available PET cameras can theoretically distinguish structures that are only 2 mm apart.

Alcohol's Acute Effects on the Brain

Both acute and chronic alcohol consumption can alter brain function - for example, changing blood flow through various brain regions and metabolic activities of those regions. PET and other neuroimaging approaches have detected such alterations, as follows:

PET analyses following alcohol consumption in social drinkers showed reduced blood flow to the cerebellum, a region at the base of the brain that controls voluntary movements and coordination. These findings may explain the muscular incoordination resulting from the consumption of alcohol.

Acute alcohol ingestion reduces the metabolic activity of the brain. The pattern of this reduced activity suggests that alcohol increases nerve signal transmission through the inhibitory neurotransmitter gamma-aminobutyric acid. This effect is more pronounced in men than in women.

Effects of Chronic Alcohol Consumption

Chronic alcohol consumption affects the brain both directly through its effects on brain cells and their functions and indirectly by causing nutritional deficiencies, liver disease, and disturbances of the hormonal and immune systems. Head trauma sustained during inebriation may also damage the brain. One approach commonly used to study the effects of long-term excessive alcohol consumption is to conduct autopsies of deceased alcoholics. Autopsy studies have demonstrated that people with a history of chronic alcohol consumption have smaller brains than age- and gender-matched nonalcoholics. Other autopsy studies have focused on alcoholics with Wernicke's encephalopathy, a severe brain disease resulting from a deficiency of the vitamin thiamine that often is associated with chronic excessive alcohol consumption. These studies have shown marked reductions in the number of neurons in the outer layer of the upper surface of the front of the brain (the superior frontal cortex), particularly in patients with liver cirrhosis. Additional autopsy studies of alcoholics with Wernicke's encephalopathy have detected reduced numbers of neurons in the cerebellum.

Although autopsy studies can provide valuable information, imaging studies in living humans beings often are preferable, particularly when investigating the progression of alcohol-related brain damage or when determining alcohol's effects on brain function. Structural imaging techniques such as CT and MRI have confirmed the findings of brain shrinkage and reduced the number of brain cells in living subjects with Wernicke's encephalopathy and other disorders associated with alcoholism. Additionally, DTI studies of alcoholics suggest the presence of abnormalities in the white matter of the brain, which consists of the extensions (axons) of neurons. Brain shrinkage and other abnormalities primarily affect the frontal lobes, although shrinkage also occurs in other brain regions in people with chronic excessive alcohol consumption.

Imaging analyses that have identified structural brain changes are complemented by functional imaging methods such as PET, which reveal changes in blood flow and other metabolic activities associated with specific sensory, motor, or cognitive functions and are impaired in people with alcohol dependence. (It is important to note, however, that neuropsychological changes may not necessarily correlate with the metabolic changes seen on PET scans of alcoholics.)

When conducting PET analyses, researchers often perform two scans on each participant to study metabolic changes throughout the brain that may be associated with particular activities. The first scan typically is performed when the patient is in a resting state to determine the basal metabolism of the stable brain. The second scan is performed during the activated condition - that is, after exposure to a psychological or pharmacological stimulus. For example, psychological activation can be accomplished by engaging the person in an activity such as viewing a videotape or performing a mental task. Alternatively, pharmacological activation may consist of administering a pharmacological agent such as an amphetamine to simulate the maximal release of dopamine in physiological excitation or stress. The findings of such analyses are summarized in the following sections.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.