‘Visualizing’ Tourette syndrome

Imaging reveals what goes on in the brain

School of Medicine neuroscientists are studying the brains of patients with Tourette syndrome to see whether they can identify differences in the dopamine system in people with the tics that characterize the syndrome.

The researchers recently received a grant from the Tourette Syndrome Association to use positron emission tomography (PET) imaging to compare dopamine release and uptake in the brains of Tourette patients to people without the syndrome to learn how the important neurotransmitter functions differently in people with the syndrome.

Movies, television shows and other popular media tend to portray people with Tourette as whooping, shuddering and cursing uncontrollably, but the syndrome often is much more subtle, according to Kevin J. Black, M.D., assistant professor of psychiatry, of neurology and of radiology.

“Imagine you’re in church during a quiet time of prayer or at the symphony during a soft section of music, and you realize you have to cough,” Black said. “You try to stifle the cough, but your body doesn’t want to cooperate. Tourette syndrome is something like that, except it’s all day, every day.”

Kevin J. Black
Kevin J. Black

Black said many people with the syndrome feel that unwanted movements or tics are not the problem as much as the uncomfortable sensations and urges to move that precede them.

Scientists once thought it was a very severe and rare condition, but now the range of severity involved in Tourette syndrome is understood to be much broader. Scientists have also discovered the number of people with the tics that characterize the syndrome is much greater than previously thought.

“Most people with Tourette syndrome function entirely normally and have a job and family,” he said. “The severity of symptoms can wax and wane over time. There are some people with very severe symptoms such as involuntary cursing, but that’s only a small minority.

“It’s much more common for people to say brief fragments of words or to sniff, cough or hum. Involuntary movements usually involve simple movements like blinking, head shaking or shoulder shrugging.”

Black and his colleagues believe one thing that may be different in people with Tourette is dopamine. Past research has shown drugs that interfere with dopamine messages in the brain also suppress tics.

Black’s research team has also noticed that increasing the brain’s dopamine levels with levodopa — a natural amino acid that has been used for many years to treat movement disorders like Parkinson’s disease — may improve tics.

Originally, the researchers worried that boosting dopamine levels with levodopa might make tics worse, but during the first several minutes after receiving the drug, researchers noticed improvement in tics.

Black’s group is conducting a clinical study to determine whether long-term treatment with levodopa might help people with Tourette keep their tics under control.

The researchers are also using imaging techniques to see what the brain does in response to levodopa. One study found that treatment with the drug helps people with the syndrome perform certain memory tasks more effectively.

By using PET imaging, researchers now want to see whether the brains of people with Tourette actually make more or less dopamine in response to levodopa or whether the difference might be downstream from dopamine production and instead involve the uptake of dopamine in key brain structures.

Working with Mark Mintun, M.D., professor of radiology and of psychiatry, Black and his colleagues will inject people who have the syndrome with a chemical marker called (11C) raclopride. Because the raclopride sticks to dopamine receptors, if dopamine release is boosted, it pushes the raclopride marker off receptors.

As neuroscientists look at PET images of the brain, they can see very bright areas that turn increasingly dimmer as dopamine is taken up by receptors and the raclopride marker is pushed out of the way.

“We’re going to give levodopa to volunteers who don’t have Tourette syndrome to see whether we can measure the boost in the brain’s dopamine levels in response to the levodopa,” Black said. “Then, we’ll do the same thing in people with tics to see whether there’s a difference in the amount of dopamine production, which we’ll measure by looking at raclopride displacement.”

If there are differences in dopamine production, it will demonstrate that something is different in how the brain produces dopamine or how the brain responds to external signals to produce dopamine in people with Tourette.

If it turns out that dopamine production is normal in patients with the syndrome, researchers will be able to move forward and look at the parts of the brain where dopamine uptake occurs.

It’s clear to Black that the dopamine system is somehow related to Tourette syndrome. What’s unclear is how it might malfunction to cause tics.

Black said this study will allow his team to see how the dopamine system changes in Tourette — and that should provide clues for the best strategies for treatment.


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