Disrupted Coupling Between the Spontaneous Fluctuation and Functional Connectivity in Idiopathic Generalized Epilepsy

Purpose: The purpose of this study was to comprehensively evaluate alterations of resting-state spontaneous brain activity in patients with idiopathic generalized epilepsy (IGE) and its subgroups (juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures (GTCS)). Methods: Resting state functional magnetic resonance imaging (fMRI) data were acquired from sixty patients with IGE and sixty healthy controls (HCs). Amplitude of low frequency fluctuation (ALFF), global functional connectivity density (gFCD), local FCD (lFCD), and long range FCD (lrFCD) were used to evaluate spontaneous brain activity in the whole brain. Moreover, the coupling between ALFF and FCDs (gFCD, lFCD, and lrFCD) was analyzed on both voxel-wise and subject-wise levels. Two-sample t-tests were used to analyze the difference in ALFF, FCDs and coupling on a subject-wise level between the two groups. Nonparametric permutation tests were used to evaluate differences in coupling on a voxel-wise level. Key findings: Patients with IGE and its subgroups showed reduced ALFF, gFCD and lrFCD in posterior regions of the default mode network (DMN). In addition, decreased ALFF and increased coupling with FCD were found in the cerebellum, while decreased coupling was observed in the bilateral pre- and postcentral gyrus in IGE compared with the coupling in HCs. Similar findings were found in the analysis between each of the two subgroups of IGE (JME and GTCS) and HCs, and JME patients had increased coupling in the cerebellum and bilateral middle occipital gyrus compared with coupling in the GTCS patients. Significance: This study demonstrated a multifactor abnormality of the DMN in IGE and emphasized that the abnormality in the cerebellum was associated with dysfunctional motor symptoms during seizures and might participate in the regulation of GSWDs in IGE.