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

Abstract

ObjectiveA 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.MethodsHere, 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.ResultsThe 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).SignificanceOur 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.

Abnormal static and dynamic functional network connectivity of the whole-brain in children with generalized tonic-clonic seizures

“…The present findings demonstrated that inter-network dFC between subnetworks in children with GTCS showed a significant increase in State 2 and a decrease in State 1 as compared to the control group. Such direction of change are consistent with previous findings that children with GTCS showed both an increase and decrease in dFC strength of some specific networks ( Li et al, 2022a , c ). However, previous studies on adults with GTCS only detected increased FC variabilities between the DMN and cognition-related networks ( Jia et al, 2020 ; Yang et al, 2021 ).…”

“…FC variability between the DMN and cognition-related networks showed a significant increase. In our previous studies, we applied the dFC method in children with GTCS to explore FC characteristics of specific networks ( Li et al, 2022a , c ). Children with GTCS showed both an increase and decrease in dFC within the DMN and the thalamocortical network.…”

“…Children with GTCS have shown some specific changes in their brain activity and topological properties of their brain network compared with adult patients. In addition, the brain’s dynamic activity changes during the resting state in children with GTCS mainly occurred in the DMN or thalamocortical network ( Li et al, 2022a , c ). The dynamic interaction among whole-brain functional networks in children with GTCS is still unclear.…”

Brain activation and connection across resting and motor‐task states in patients with generalized tonic–clonic seizures

“…Here, we found that patients failed to flexibly change the network reorganization across resting and motor states, which might be related to the hyper‐integration of brain networks caused by disease. 54 At the same time, we also discovered the instability of the patient's functional activity across states, which was found to be contrary to changes observed in spatial profiles of brain network. Distributed decreased across‐state connectivity in patients with GTCS also suggested the instability of the epileptic brain induced by motor tasks.…”

“…Frontotemporal regions are involved in the majority of patients with generalized epilepsy, 52,53 which might lead to a fixed and over‐integrated network architecture in epilepsy. Here, we found that patients failed to flexibly change the network reorganization across resting and motor states, which might be related to the hyper‐integration of brain networks caused by disease 54 . At the same time, we also discovered the instability of the patient's functional activity across states, which was found to be contrary to changes observed in spatial profiles of brain network.…”