Yale Bulletin and Calendar

November 14, 2003|Volume 32, Number 11

'Puzzling' new find may aid patients
with Tourette's Syndrome

Yale researchers have observed an increased number of neurons in the brains of patients with Tourette's Syndrome (TS), a finding that could lead to deeper understanding of how the brain compensates for symptoms of the disorder.

The results of the study were presented at the Society for Neuroscience Conference Nov. 12 in New Orleans, Louisiana.

"This is the first time we've been able to look at the actual number of neurons in patients with Tourette's Syndrome," says principal investigator Dr. Flora M. Vaccarino, associate professor in the Yale Child Study Center and in the Department of Neurobiology at the School of Medicine.

TS is a neurological disorder characterized by tics -- involuntary, rapid, sudden movements or vocalizations that occur repeatedly in the same way. This disorder is often seen in young children and it might be a result of problems in brain development. An affected region, the basal ganglia, which initiates or inhibits action plans, lies deep in the center of the brain. Neurons in the basal ganglia perform this feat by processing the information they receive from the "executive centers" in the brain's prefrontal cortex and sending it back to motor and sensory areas of the cortex through another set of nuclei in a structure called the thalamus.

Vaccarino and her team analyzed postmortem brain tissue. They found the increase in neurons in the internal segment of the globus pallidus, a part of the basal ganglia that directly connects to the thalamus and inhibits its function.

The study results showed that compared to normal specimens, TS subjects have an approximately 60% increase in number and density of neurons in the internal segment of the globus pallidus.

"We're quite puzzled by these findings," says Vaccarino. "We were expecting to find a loss of neurons in this region. Normally neurons in the internal segment of the globus pallidus inhibit the thalamus and the cerebral cortex, while the tics of TS are thought to be due to increased activity in these regions. Surprisingly, additional data confirmed that TS patients have approximately twice as many inhibitory neurons as the control group."

Vaccarino says the results are based on a limited number of subjects and more research is needed in this area. She points to two things that are helpful in interpreting the data: In Parkinson's disease, there is a decrease in inhibitory neurons in this region of the basal ganglia and patients lack a neurotransmitter called dopamine, which normally stimulates movements by inhibiting neurons in the globus pallidus. TS patients, on the other hand, appear to have more dopamine in the basal ganglia, which may explain their tics. Vaccarino says it is possible that somehow neurons in the globus pallidus increase in number in response to the increase in dopamine. Whether dopamine is the cause of this phenomenon, and how the increase in globus pallidus neurons actually occurs, have yet to be determined.

"We analyzed adult brains, so the patients had Tourette's for many years. The increased number of neurons may serve a compensatory function," says Vaccarino. "The next step is to increase the number of brains studied, which may allow us to draw a correlation between symptom severity and anatomical findings. We also need to examine other areas of the basal ganglia, ideally to draw a correlation between neuronal number and the extent of dopamine projections to the basal ganglia."

"If our hypothesis turns out to be correct, it would suggest that the brain uses unexpected mechanisms for compensating for the symptoms of TS, which may explain why the severity of symptoms generally decreases with age in this disorder," says Vaccarino. "The level of dopamine is known to gradually decline throughout adulthood."

The study was made possible by patients and their families who donated brains to the brain bank sponsored by the Tourette's Syndrome Association. Normal control brains were collected through the Center for Critical Technologies at Yale and the Harvard Tissue Bank.

Study co-investigators included Dr. Wei Zheng and Dr. James Leckman at Yale; and Clifford Saper and Marion Difiglia at Harvard.

-- By Karen Peart

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