Developmental Trajectories of Dynamic Brain Network Organization and Their Alteration in Tourette Syndrome

<jats:p>Typical brain network maturation involves an increase in network flexibility and hemispheric specialization. Tourette syndrome (TS) disrupts these trajectories, with tic severity potentially modulating deviations. This study examined theta-band EEG source connectivity states in typically developing children and children with TS. We assessed age-related trajectories and the impact of tic severity using generalized linear modeling, accounting for sex and multiple comparisons. K-means clustering identified four recurrent source connectivity states (A-D), with metrics including Coverage, representing state prevalence (proportion of time spent in each state), Average Dwell Time, an index of state stability (mean duration of stable persistence of each state), and Transition Rate Per Minute, reflecting global network flexibility (frequency of state switches per minute). In healthy controls (HC), typical maturation was characterized by increased left intra-hemisphere connectivity state stability and prevalence, decreased diffuse connectivity state stability, and rising network flexibility. TS patients exhibited deviant trajectories, including age-dependent decreasing global network flexibility across subgroups stratified by tic severity and marginally divergent diffuse activity patterns, with high-severity cases showing increased diffuse connectivity state stability. The normative patterns suggest typical motor development requiring dynamic network reconfiguration and hemispheric specialization, processes that appear altered in TS. TS patients exhibit age-dependent network rigidity across severity subgroups, as reflected by decreased transition rates, alongside severity-modulated network imbalances, indicating that tic disorders disrupt mechanisms of brain network maturation underlying motor control. These findings suggest that atypical trajectories of network stability and flexibility represent a key feature of tic pathophysiology, highlighting the role of altered network dynamics in TS during maturation.</jats:p>