Reconfiguration of static and dynamic thalamo-cortical network functional connectivity of epileptic children with generalized tonic-clonic seizures

OBJECTIVE: A number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS. METHODS: Here, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed. RESULTS: The static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time). SIGNIFICANCE: Our findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children.