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Source: Washington University School Of Medicine

Brain Activity, Including Memory-processing, Changes In Tourette
Syndrome

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.