A Critical Role of Action-Related Functional Networks in Gilles de la Tourette Syndrome

Gilles de la Tourette Syndrome (GTS) is the most severe form of chronic tic disorders, characterized by uncontrollable motor actions and vocalizations. While brain stimulation techniques show promise in reducing tic severity, optimal target networks are not well-defined. Here, we leveraged datasets from two independent deep brain stimulation (DBS) cohorts and a cohort of tic-inducing lesions to infer critical networks for treatment and occurrence of tics by mapping stimulation sites and lesions to a functional connectome derived from 1,000 healthy participants. We found that greater tic reduction is linked to higher connectivity of DBS sites (N = 37) with action-related functional resting-state networks, i.e., the cingulo-opercular (R = 0.62; p < 0.001) and somato-cognitive action networks (R = 0.47; p = 0.002). Hubs within the cingulo-opercular network best matched the optimal connectivity profiles of thalamic DBS. We replicated the significance of targeting cingulo-opercular and somato-cognitive action network connectivity in an independent DBS cohort (N = 10). Finally, we demonstrate that tic-inducing brain lesions (N = 22) exhibit similar connectivity to these networks. Collectively, these results suggest a critical role for these action-related networks in the pathophysiology and treatment of GTS.