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Advances In Understanding Brain Circuits Responsible For Tics In Tourette's Shed Light On Disorder

November 3, 2004
Society For Neuroscience
Cell transplants, silencing mutant genes, and use of a neuron support factor may represent new ways to treat the fatal brain disorder amyotrophic lateral sclerosis (ALS).

Recent advances are producing a much greater understanding of the brain circuits responsible for the tics and problem behaviors seen in Tourette's syndrome.

In one groundbreaking study, investigators have for the first time measured the number of neurons in a particular area of the basal ganglia-the brain area involved in Tourette's-in patients with the disorder. Other studies suggest an imbalance in the basal ganglia's inhibitory function could interfere with its ability to suppress unwanted movements and vocalizations and thus lead to Tourette's syndrome.

One of the least understood brain disorders, Tourette's syndrome affects about one in 200 children. Symptoms usually appear between the ages of four and eight and include repetitive involuntary movements and utterances, or “tics.” Tics vary according to where, how often, and how strongly they are expressed. They are often preceded by a sensory cue or “urge to tic” that can besiege the individual's consciousness. Tics wax and wane in severity and are typically worse during periods of emotional stress or fatigue.

Although many children experience their worst symptoms around the age of 10 or 11 and then improve, some patients show their worst symptoms as adults. In its most extreme form, the tics can be virtually nonstop and include “purposive”-appearing repetitive behaviors including obscene or socially inappropriate speech and more rarely self-injurious behaviors. In addition to tics, individuals with Tourette's also often have obsessions, compulsions, and attentional deficits.

Scientists now know that symptoms of Tourette's syndrome likely arise from dysfunction in a region deep within the brain called the basal ganglia. Neurons in the basal ganglia inhibit or initiate action plans 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 the thalamus, new studies suggest.

“Recent imaging and postmortem studies now implicate the ventral striatum and caudate nucleus—two regions of the basal ganglia—as areas associated with the brain dysfunction seen in Tourette's,” says Neal Swerdlow, MD, PhD, of the University of California-San Diego department of psychiatry, co-chair of a symposium at the Society for Neuroscience annual meeting titled “Tourette's: The Self Under Seige.”

“Although there is general agreement that the basal ganglia are implicated in Tourette's syndrome, we know relatively few details. For example, we know that increased activation in the caudate and prefrontal cortex is associated with better tic control,” says James Leckman, MD, of the Yale University School of Medicine Child Study Center and co-chair of the symposium. “There is also evidence that the actual size of the caudate nucleus is reduced in many individuals with Tourette's. But we don't know how these findings are linked to the clinical features of Tourette's including its waxing and waning course and why the tic symptoms usually peak in early adolescence.”

Knowing that dopamine antagonist drugs reduce the tics associated with Tourette's and that selective serotonin reuptake inhibitors reduce the symptoms of obsession and compulsions, Roger Albin, MD, and colleagues at the University of Michigan department of neurology investigated the idea that the ventral striatum—a brain region where both dopamine and serotonin have important functions—could be involved in Tourette's syndrome.

Noninvasive imaging studies show that the ventral striatum of Tourette's patients has an excessive amount of dopamine-containing nerve terminals. Other studies suggest that in normal brain development, dopamine-containing nerve terminals are overproduced in the years leading up to adolescence, and that these nerve terminals are pruned back during adolescence.

“This raises the possibility that Tourette's syndrome is due partly to abnormal persistence of excessive dopamine terminals in the ventral striatum due to subtle changes in the timing of brain development,” Albin says.

The ventral striatum is known to be involved in the formation of habits and is also involved in repetitive, stereotyped movements of the face and limbs, some of which may be socially significant, Albin says. “The tics of Tourette's syndrome may disrupt the unconscious social communication normally mediated by these facial movements, head position, and other stereotyped movements,” he says. “This could be the basis for the perception of tics as disruptive.”

In other work, Flora Vaccarino, MD, also of the Yale University School of Medicine Child Study Center, shows that patients with Tourette's have an increased number of neurons that normally silence brain activity in the internal segment of the globules pallidus and a decrease in neurons in the caudate nucleus.

Using postmortem brain tissue, Vaccarino and her colleagues found that Tourette's syndrome patients had about twice as many inhibitory neurons in the globus pallidus, a part of the basal ganglia that connects to the thalamus and inhibits its function. Inhibitory neurons were decreased in other areas of the basal ganglia, including the caudate nucleus, says Vaccarino.

Vaccarino suggests that the imbalance in inhibitory neurons could change the timing of activity in the basal ganglia and thus lead to the tics and other compulsive symptoms of Tourette's syndrome.

“The next step is to increase the number of brains studied, which may allow us to relate severity of symptoms and anatomical findings,” Vaccarino says.

Leckman and his colleagues at Yale and Columbia University studied patients who had had brain images taken during childhood to determine if the size of any basal ganglia structures measured before the age of 14 predicted their outcome years later as they entered adulthood. Based on the earlier studies, they predicted that caudate volumes would influence the course of the disorder.

“We found that the volume of the caudate nucleus and adjacent structures in the subgenual region, which includes areas of the ventral striatum and the limbic cortex, could account for nearly a third of the variance of tic severity at follow-up,” says Leckman. These striatal and limbic regions are involved in the processing of motivational and affective cues, which in turn may contribute to the well-known sensitivity of Tourette's patients to emotionally laden stimuli.

One of the challenges facing a complex nervous system with the capability for many different behaviors is the need to prevent potentially competing behaviors from interfering with desired behaviors, says Jonathan Mink, MD, PhD, of the University of Rochester Medical School department of child neurology. Mink hypothesizes that a central role of the basal ganglia is to facilitate desired behaviors and inhibit those that might compete with the desired behavior. In Tourette's syndrome, clusters of neurons in the ventral striatum of the basal ganglia may become abnormally active, leading to inhibition of neurons in the globus pallidus and substantia nigra (the basal ganglia's output centers).

“Neurons in these areas normally act to suppress unwanted movements,” says Mink. “But when the neurons themselves are inhibited, they can no longer act to suppress unwanted movements, leading to tics.”

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The above story is based on materials provided by Society For Neuroscience. Note: Materials may be edited for content and length.

Cite This Page:

Society For Neuroscience. "Advances In Understanding Brain Circuits Responsible For Tics In Tourette's Shed Light On Disorder." ScienceDaily. ScienceDaily, 3 November 2004. <www.sciencedaily.com/releases/2004/10/041030133244.htm>.
Society For Neuroscience. (2004, November 3). Advances In Understanding Brain Circuits Responsible For Tics In Tourette's Shed Light On Disorder. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2004/10/041030133244.htm
Society For Neuroscience. "Advances In Understanding Brain Circuits Responsible For Tics In Tourette's Shed Light On Disorder." ScienceDaily. www.sciencedaily.com/releases/2004/10/041030133244.htm (accessed September 16, 2014).

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