Aberrant brain functional connectivity is associated with clinical symptoms in tourette syndrome: a triple network model perspective.

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor/vocal tics and premonitory urges. The triple network model (TNM)-including the salience network (SAN), frontoparietal network (FPN, also known as control network, Con), and default mode network (DMN)-provides a framework for understanding large-scale brain dysfunction. However, the TNM's role in the "urge-to-tic" mechanism in pediatric TS remains unclear. This study aimed to characterize network-level functional connectivity (FC) within the TNM in pediatric TS, examine its associations with clinical symptoms, and propose a refined neurobiological hypothesis for the urge-to-tic process. We enrolled 68 children with TS and 65 matched controls. Resting-state fMRI was used to quantify FC within the TNM. Clinical severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), and Sensory Phenomenon Assessment Scale (SPAS). Group differences in FC were identified, and random forest (RF) regression models were employed to predict symptom severity based on FC within the TNM. Children with TS exhibited significant inter-network FC alterations, specifically involving increased connectivity between the left DMN and bilateral SAN. While YGTSS and SPAS score were significantly associated with TNM connectivity, no significant correlation was found with PUTS scores. The RF models successfully predicted YGTSS (R2 = 0.169) and SPAS scores (R2 = 0.139), with the left DMN-right SAN circuit emerging as the most robust predictor. TNM dysconnectivity is a core neural signature of pediatric TS, highlighting the TNM as a crucial framework for understanding the pathophysiology of the "urge-to-tic" process.