St. Louis, April 5, 2004 -- Scientists have known for years that abnormal activity involving a brain chemical called dopamine is somehow connected to the movements and vocalizations, or tics, associated with Tourette syndrome. Now neuroscience researchers at Washington University School of Medicine in St. Louis have found brain activity in these patients is abnormal during memory tasks, as well.
The researchers also found that giving Tourette syndrome patients the drug levodopa, which is used to treat abnormal dopamine activity in conditions such as Parkinson's disease, normalized brain activity during the memory tasks.
"We've observed in the living brain a dopamine-sensitive abnormality in people with tics. That's been hypothesized for 40 years, but this is the first time it's been demonstrated," says principal investigator Kevin J. Black, M.D., assistant professor of psychiatry, neurology and radiology and staff physician at Barnes-Jewish Hospital. "We actually have a direct demonstration of abnormal brain activation in people with Tourette syndrome that is corrected when they are given a dopamine-type medicine."
The study is published online and will appear in the May issue of the journal Biological Psychiatry.
Using functional magnetic resonance imaging (fMRI), the researchers compared eight adults with Tourette syndrome to 10 age- and gender-matched individuals without tics. Brain scans were taken while participants performed a memory task that involved remembering and identifying letters on a computer screen. The task measures working memory, a type of short-term memory that involves concentration on several things at once.
"We chose to look at the brain's response to a working memory task because past research has shown that working memory could be affected by dopamine levels in the brain," says first author Tamara Hershey, Ph.D., assistant professor of psychiatry and neurology at the School of Medicine. "We also know dopamine is involved in tics, but if we had studied a task that involved movement, for example, the fact that some tics involve movement could have made it harder to interpret the differences in brain activity."
In terms of speed and accuracy during the memory task, there were no differences between the two groups, but fMRI scans revealed that several brain areas were more active in Tourette syndrome patients than healthy participants.
The clearest differences were in a brain region called the parietal cortex, located at the top of the brain roughly in between the front and back of the head. Tourette syndrome patients also had increased activity in the medial frontal gyrus and in the thalamus -- which acts as the brain's relay station between the outer layer, or cortex and the rest of the nervous system.
"People with tics performed this task just as well as people without, so it's not something that involves a difference in output," Black says "Therefore, we believe any differences we saw in the fMRI scans reflect changes in the way the brain is working."
To determine whether the results were related to dopamine abnormalities, Hershey, Black and colleagues gave all participants an intravenous infusion of the drug levodopa.
When the two groups then repeated the original working memory task, brain activity in healthy participants was unchanged. In TS patients, however, the areas that had been abnormally overactive were substantially less active after treatment.
"Levodopa seems to normalize the excess activity we had seen in the parietal cortex in the group with tics," Hershey says. "There were changes in activity in the other structures, too, but the changes in the parietal cortex were the most dramatic."
Before decoding which brain scans belonged to which participants, Black looked at the patients' medical histories and used a standard method of rating the severity of their illness. He found that those with the most severe history of Tourette syndrome had the largest post-levodopa decreases in brain activity during the working memory task.
Now that they know the brain functions differently in people with Tourette syndrome, Black and Hershey plan to look at brain activity during different tasks to see whether they can find more dopamine-related differences.
Black also is finalizing a treatment study to determine if levodopa helps control tics in Tourette syndrome patients. That study should be completed later this year.
Hershey T, Black KJ, Hartlein JM, Barch DM, Braver TS, Carl JL, Perlmutter JS. Cognitive-Pharmacologic Functional Magnetic Resonance Imaging in Tourette Syndrome: A Pilot Study. Biological Psychiatry, May 1, 2004.
This research was supported by a Young Investigator award from the National Alliance for Research on Schizophrenia and Depression, by the Greater St. Louis Chapter of the American Parkinson's Disease Association (ADPA), the National Institutes of Health, the Parkinson's Disease Foundation, the Charles A. Dana Foundation and the ADPA Advanced Center for Parkinson's Disease Research at Washington University. The Tourette Syndrome Association provided recruitment support.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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