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| Kevin Black |
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 University neuroscience researchers have found that 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 memory tasks.
“That’s been hypothesized for 40 years, but this is the first time it’s been demonstrated. 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.”“We’ve observed in the living brain a dopamine-sensitive abnormality in people with tics,” said principal investigator Kevin J. Black, M.D., assistant professor of psychiatry, of neurology and of radiology.
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 healthy adults the same age and gender.
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,” said first author Tamara Hershey, Ph.D., assistant professor of psychiatry and neurology.
“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 in healthy participants.
The clearest differences were in a brain region called the parietal cortex, 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 said.
“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 their colleagues gave all participants an intravenous infusion of the drug levodopa.
When the two groups repeated the original working memory task, brain activity in healthy participants was unchanged.
In Tourette 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 said. “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.
Black and Hershey plan to look at brain activity during different tasks to see whether they can find more dopamine-related differences.
Black is also finalizing a treatment study to determine if levodopa helps control tics in Tourette syndrome patients.
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