Summary: Researchers use a new computer based brain stimulation to demonstrate tics associated with Tourette syndrome as a result of interaction between multiple brain regions.
Model predictions could pave the way to new treatments.
A new computer-based brain simulation shows that motor tics in Tourette syndrome may arise from interactions between multiple areas of the brain, rather than a single malfunctioning area, according to a study published in PLOS Computational Biology.
Tourette syndrome causes people to have involuntary motor tics, such as eye blinking, sniffing, or clapping. Traditionally, such tics were associated with dysfunction of a brain region known as the basal ganglia, but recent studies of rat, monkey, and human brains suggest that the cerebellum, thalamus, and cortex may be involved, too.
Based on this recent evidence, Daniele Caligiore of the National Research Council, Italy, and colleagues developed a computer simulation of brain activity that underlies motor tics in Tourette syndrome. This model reproduces neural activity that was associated with tics in a recent study of the monkey brain, which showed that tics might also involve signaling between the cortex, basal ganglia, and cerebellum.
By tweaking the model to accurately reproduce the results of the monkey study, the researchers were able to use it to better understand how the brain might generate tics. The model suggests that abnormal dopamine activity in the basal ganglia works in tandem with activity in the thalamo-cortical system to trigger a tic. Meanwhile, the model suggests, the basal ganglia-cerebellum link discovered in the monkey study may allow the cerebellum to influence tic production, as well.
“This model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links,” Caligiore says.
The researchers also found that the model can be used to predict the number of tics generated when there are dysfunctions in the neural circuits that connect the basal ganglia, thalamus, cortex, and cerebellum. These predictions could aid identification of new brain regions that could serve as targets of new treatments to reduce motor tics.
Caligiore says the model represents a first step toward building “virtual patients” to test potential therapies via computer simulations. “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,” he says.
Funding: DC and FM were supported by the European Commission under the 7th Framework Programme (FP7/2007-2013), ICT Challenge 2 “Cognitive Systems and Robotics”, project “IM-CLeVeR – Intrinsically Motivated Cumulative Learning Versatile Robots”, grant agreement no. ICT-IP-231722 and by the EU FET Open project GOAL-Robots – Goal-based Open-ended Autonomous Learning Robots n. 713010; MAA was supported by the National Science Foundation under Grant No. BCS-1343544 “INSPIRE Track 1: Action, Vision and Language, and their Brain Mechanisms in Evolutionary Relationship”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Source: Daniele Caligiore – PLOS
Image Source: NeuroscienceNews.com image is credited to Beste Özcan.
Original Research: Full open access research for “Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome” by Daniele Caligiore, Francesco Mannella, Michael A. Arbib, and Gianluca Baldassarre in PLOS Computational Biology. Published online March 30 2017 doi:10.1371/journal.pcbi.1005395
Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome
Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.
“Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome” by Daniele Caligiore, Francesco Mannella, Michael A. Arbib, and Gianluca Baldassarre in PLOS Computational Biology. Published online March 30 2017 doi:10.1371/journal.pcbi.1005395