Functional and structural connective disturbance of the primary and default network in patients with generalized tonic-clonic seizures

•Patients with GTCS demonstrated disturbed functional degree centrality in regions involved in the primary network (PN), default mode network (DMN), and salience network (SN).•The connective analysis revealed hyper-connectivity in the PN, hypo-connectivity in DMN, and increased connectivity between two of them.•Abnormal gray matter volume correlated with the functional connectivity, implying potential anatomic substrates underlying the disease.•The insula showed unbalanced connectivity with DMN and PN in patients. The present study aims to investigate the disturbance of functional and structural profiles of patients with generalized tonic-clonic seizures (GTCS). Resting-state fMRI and diffusion tensor imaging (DTI) data was collected from fifty-six patients and sixty-two healthy controls. Degree centrality (DC) of functional connectivity was first calculated and compared between groups using a two-sample t-test. Furthermore, the regions with significant alteration of DC in patients with GTCS were used as nodes to construct the brain network. Functional connectivity (FC) network was constructed using the Person’s correlation analysis and structural connectivity (SC) network was obtained using deterministic tractography technology. Gray matter volume (GMV) and cortical thickness (CT) were computed and correlated with connective profiles. The patients with GTCS showed increased DC in the primary network (PN), including bilateral precentral gyrus, supplementary motor areas (SMA), and visual cortex, and decreased DC in core regions of default mode network (DMN), bilateral anterior insular, and supramarginal gyrus. In the present study, 14 regions were identified to construct networks. In patients, the FC and SC were increased within the sensorimotor network (mainly linking with SMA) and decreased within DMN (mainly linking with the posterior cingulate cortex (PCC)). Except for the decreased FC and SC between cerebellum and SMA, patients demonstrated increased connectivity between DMN and PN. Besides, the insula demonstrated decreased FC with DMN and increased FC with PN, without significant SC alterations in patients with GTCS. Decreased GMV in bilateral thalamus and increased GMV in frontoparietal regions were found in patients. The decreased GMV of thalamus and increased GMV of SMA positively and negatively correlated with the FC between PCC and left superior frontal cortex, the FC between SMA and left precuneus respectively. Hyper-connectivity within PN help