Tourette syndrome is a neurological disease in which patients make a series of repetitive, involuntary movements and sounds that are commonly referred to as ‘tics’. A new study uses a computational model to simulate the neurological basis for the illness, which could help researchers to design new therapies in the future.
The Centers for Disease Control and Prevention (CDC) report that in the United States, 1 in 360 children aged between 6 and 17 years receive a Tourette syndrome diagnosis. However, the CDC also suggest that the numbers may be higher than this, as the disease often goes undiagnosed.
The tics that accompany the disease vary in complexity. Some of them can be fairly simple – such as blinking, for instance – while others may involve touching objects, repeating the same words, or making obscene gestures.
Some of the motor tics that occur in the disease – such as sniffing, blinking, grimacing, or shrugging – were, until now, thought to occur in a single area of the brain called the basal ganglia.
The basal ganglia is a group of interconnected subcortical nuclei – found at the base of the forebrain, deeply embedded in the brain’s hemispheres – that are involved in motor control and other executive functions and behaviors.
The new research, however, suggests that the syndrome is not restricted to a single region, but it may be associated with multiple areas of the brain that interact to cause the tics.
The findings were published in the journal PLOS Computational Biology, and the research team was led by Daniele Caligiore of the National Research Council in Italy.
Caligiore and team developed a computer simulation of the neural activity underlying the Tourette-related motor tics.
The new model builds on previous research that revealed the brain activity that accompanies motor tics in monkeys’ and rats’ brains. These previous studies suggested that signaling between the cortex, cerebellum, and basal ganglia might be responsible for the tics.
In the new study, Caligiore and colleagues adjusted the model to replicate the main functional and anatomical elements of the neural system examined in animal studies: the basal ganglia, the thalamus, the primary motor cortex, and the cerebellum.
Not only did the new model manage to reproduce the results of the monkey study, but it also served to highlight the key role played by the interaction between various brain regions in triggering the Tourette-related motor tics.
Specifically, the model revealed that the neural pathway connecting the subthalamus with the pons and the cerebellum – in tandem with the neural circuit going from the cerebellum to the thalamus and the cortex – may be responsible for the tics. Additionally, the study suggests that tics may be caused by a combination of abnormal dopamine signaling in the basal ganglia and activity in the cerebello-thalamo-cortical circuit.
As the authors explain:
“The model predicts that the interplay between dopaminergic signals and cortical activity may underlie the emergence of tic events, and that the anatomical connection linking subthalamic nucleus and cerebellum may support the involvement of the cerebellum in tic production. In this way, the model supports the claim […] about a possible involvement of the subthalamic-pons-cerebellar circuit in tic generation. ”
To the authors’ knowledge, this is the first time that a computational model has been used to study these pathways. “This model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links,” says the lead author of the study.
The findings have not only provided the basis for future experiments, but they also pave the way for novel therapies. As Caligiore and colleagues explain:
“The model predicts that tic production could be reduced by externally stimulating or inhibiting the primary motor cortex. These predictions could be important for identifying new target areas, aside [from] the traditional ones to design innovative system-level therapeutic actions.”
Additionally, the study’s lead author anticipates that the findings could help to create so-called virtual patients, which could serve to test therapies using computer models in a cost-effective and ethical way.
“These simulations can be performed with little costs and no ethical implications and could suggest promising therapeutic interventions to be tested in focused investigations with real patients,” Caligiore says.