Alterations in basal ganglia-cerebello-thalamo-cortical connectivity and whole brain functional network topology in Tourette's syndrome

Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by the presence of motor and vocal tics. Major pathophysiological theories posit a dysfunction of the cortico-striato-thalamo-cortical circuits as being a representative hallmark of the disease. Recent evidence suggests a more widespread dysfunction of brain networks in TS including the cerebellum and going even beyond classic motor pathways. In order to characterize brain network dysfunction in TS, in this study we investigated functional and effective-like connectivity as well as topological changes of basal ganglia-thalamo-cortical and cortico-cerebellar brain networks. We collected resting-state fMRI data from 28 TS patients (age: 32 ± 11 years) and 28 age-matched, healthy controls (age: 31 ± 9 years). Region of interest based (ROI-ROI) bivariate correlation and ROI-ROI bivariate regression were employed as measures of functional and effective-like connectivity, respectively. Graph theoretical measures of centrality (degree, cost, betweenness centrality), functional segregation (clustering coefficient, local efficiency) and functional integration (average path length, global efficiency) were used to assess topological brain network changes. In this study, TS patients exhibited increased basal ganglia-cortical and thalamo-cortical connectivity, reduced cortico-cerebellar connectivity, and an increase in parallel communication through the basal ganglia, thalamus and cerebellum (increased global efficiency). Additionally, we observed a reduction in serial information transfer (reduction in average path length) within the default mode and the salience network. In summary, our findings show that TS is characterized by increased connectivity and functional integration of multiple basal ganglia-thalamo-cortical circuits, suggesting a predominance of excitatory neurotransmission and a lack of brain maturation. Moreover, topological changes of cortico-cerebellar and brain networks involved in interoception may be underestimated neural correlates of tics and the crucial premonitory urge feeling.