How Do Tics Develop in Tourette Syndrome?

Tourette syndrome is a brain dysfunction that leads to involuntary motor tics, such as sniffing, blinking, or clapping. In about 10 percent of cases, it also leads to the spontaneous utterance of taboo words or phrases, known as coprolalia. Until recently, these tics were believed to be the result of a dysfunction primarily in a brain structure known as the basal ganglia—a brain region associated with voluntary motor control, which primarily uses the neurotransmitter gamma-aminobutyric acid (GABA) to function. Recent studies of rat, monkey, and even human brains, however, has suggested that the tics stem from a more complex, system-level dysfunction that involves the cerebellum, the thalamus, and the cortex, which are all connected.

To better explore these brain regions and their influence on Tourette syndrome, Daniele Caligiore, a researcher at the Institute of Cognitive Sciences and Technologies of the Italian National Research Council in Italy, and his colleagues created a computer-simulated model of the neural activity of a brain with Tourette syndrome. The results are published in PLOS Computational Biology.

“The model presented here is a first step of a research agenda aiming at building virtual patients, allowing us to test potential therapies by using computer simulations,” Caligiore tells mental_floss. This method can be performed at low cost, without ethical implications, and, he hopes, help develop “more effective therapeutic protocols, and suggest promising therapeutic interventions.”

Using a computer programming language called Python, Caligiore’s team built an artificial neural network model. In it, each neuron has a behavior that is regulated by mathematical equations. He explains, “Once built, the model works like a computer program—you can run it and observe its behavior.”

Caligiore reproduced the brain activity from monkey studies, published in the Journal of Neuroscience, in which an agent called bicuculline was microinjected into a region of the brain called the sensorimotor striatum that is involved in motor function. The researchers found that this microinjection of bicuculline inhibits GABA, which causes an abnormal release of the neurotransmitter dopamine.

“This excess [dopamine] might cause an abnormal functioning of the basal ganglia-thalamo-cortical circuit, leading to the production of tics,” Caligiore says. The abnormal dopamine release is one necessary condition for a tic, but it's not the only one, he says. “To have a motor tic you need both abnormal dopamine and a background activity in the motor cortex (due to the neural noise) above a threshold.”

In other words, “it is not just a matter of dopamine or just a matter of abnormal cortical activity," he explains. "It is a necessary combination of both.”

Caligiore’s team also found that the cerebellum appeared to influence tic production as well. Their model shows that during a tic, there is abnormal activity in a region of the basal ganglia called the subthalamic nucleus (STN). The STN connects with the cerebellum. “This is a possible reason [for a tic] because there is an abnormal tic-related activity in the cerebellum as well.”

What the computer model shows is that motor tics in Tourette syndrome “are generated by a brain system-level dysfunction, rather than by a single area malfunctioning as traditionally thought.” Studying this interaction between regions “could substantially change our perspective about how these areas interact with each other and with the cortex,” he adds.

Moreover, Caligiore’s team’s computer model is a noninvasive, ethical, and low-cost way to study these brain systems—and it certainly could be the first important step to identify new target areas for future therapies.