Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

Abstract

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.

Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome

“…Our results provide further support for the involvement of the basal ganglia across all disorders analyzed here. Dysfunction of the basal ganglia has been observed in all four studied disorders (69)(70)(71)(72). Interestingly, our analyses also implicate the involvement of the hypothalamus-pituitary-adrenal (HPA) axis, in accordance with previous studies implicating this system in multiple childhood-onset psychiatric traits including ADHD and TS (73)(74)(75)(76)(77).…”

Does neuropsychological performance in OCD relate to different symptoms? A meta-analysis comparing the symmetry and obsessing dimensions

“…Symmetry behavior has been associated with activity in the DLPFC, medial thalamus, parietal and motor regions in healthy individuals (de Vries et al., ), OCD samples (Rauch et al., ; van den Heuvel et al., ), and related psychopathology (Suda et al., ). Additionally, all of these regions are thought to be in involved in tic disorders, a psychopathology more related to OCD with S/O symptoms (Caligiore, Mannella, Arbib, & Baldassarre, ; Peterson et al., ; Singer, ; Stern et al., ). The sensory experiences reported in NJREs have often been compared to premonitory urges seen in tic disorders (Leckman et al., ; Prado et al., ).…”

“…Additionally, all of these regions are thought to be in involved in tic disorders, a psychopathology more related to OCD with S/O symptoms (Caligiore, Mannella, Arbib, & Baldassarre, 2017;Peterson et al, 1998;Singer, 2005;Stern et al, 2000). The sensory experiences reported in NJREs have often been compared to premonitory urges seen in tic disorders (Leckman et al, 1994;Prado et al, 2008).…”

Entraining movement-related brain oscillations using rhythmic median nerve stimulation

“…First, the direct prediction arising from a recent computational model that the occurrence of motor tics in TS could be effectively reduced by externally stimulating the sensorimotor cortex (Caligiore, Mannella, Arbib, Baldassarre, 2017) and second, the recent empirical finding that compensatory alterations in TS may be associated with increased beta synchronization in patients with TS. Specifically, the finding that increased beta power was associated with reduced tic severity in TS (Niccolai, van Dijk, Franzkowiak, Finis, Südmeyer, Jonas, et al, 2016).…”