Frequency-Dependent Changes in Interhemispheric Functional Connectivity Measured by Resting-State fMRI in Children With Idiopathic Generalized Epilepsy.

Lin Jiang,Hongjian Luo,Guoming Zhang,Tijiang Zhang,Shiguang Li,Yanan Wang,Xuejin Ma

doi:10.3389/fneur.2020.00645

Abstract

Epilepsy is associated with abnormal spatiotemporal changes in resting-state brain connectivity, but how these changes are characterized in interhemispheric coupling remains unclear. This study aimed to characterize frequency-dependent alterations in voxel-wise mirrored homotopic connectivity (VMHC) measured by resting-state functional magnetic resonance imaging (rs-fMRI) in children with idiopathic generalized epilepsy (IGE). Rs-fMRI data were collected in 21 children with IGE and 22 demographically matched children with typical development. We used three resting-state frequency bands (full, 0.01–0.08 Hz; slow-4, 0.027–0.073 Hz; slow-5, 0.01–0.027 Hz) to compute VMHC and locate the significant foci. Voxel-wise p <0.001 and cluster-level p <0.05 cluster-level family-wise error correction was applied. In between-group comparisons, we identified that the full and higher frequency (slow-4) bands showed similar reductions in VMHC including Rolandic operculum, putamen, superior frontal, lateral parietal, middle cingulate, and precuneus in children with IGE. In the lower frequency band (slow-5), we identified specific reductions in VMHC in orbitofrontal and middle temporal gyri in children with IGE. Further analyses on main effects and interaction between group and frequency band suggested significant frequency-dependent changes in VMHC, and no significant interaction was found. The results were generally similar with global brain signal regression. Additional association analysis showed that VMHC in the putamen within the full and slow-4 bands was significantly positively correlated with chronological age in children with IGE, and the same analysis was non-significant in the controls; VMHC in the medial prefrontal region in the slow-4 band was significantly positively correlated with IQ performance sub-score. Our findings suggest that IGE children show frequency-dependent changes in interhemispheric integration that spans regions and systems involving cortical-subcortical, language, and visuomotor processing. Decreased functional coupling within the dorsal striatum may reflect atypical development in children with IGE.

Highlights

Idiopathic generalized epilepsy (IGE) is characterized by generalized spike-wave discharges on normal electroencephalography (EEG) and accounts for 15–20% of all epilepsies [1], with no identifiable causes other than genetic factors [2, 3]
In the conventional low-frequency band (0.01– 0.08 Hz), we found significantly decreased voxelmirrored homotopic connectivity (VMHC) in Rolandic operculum, supramarginal gyrus, putamen, middle orbitofrontal, superior parietal, and middle cingulate regions in children with idiopathic generalized epilepsy (IGE) (Figure 1, Table 2)
We investigated interhemispheric Functional connectivity (FC) across different frequency bands with resting-state functional magnetic resonance imaging (rs-functional magnetic resonance imaging (fMRI)) in children with IGE

Summary

Introduction

Idiopathic generalized epilepsy (IGE) is characterized by generalized spike-wave discharges on normal electroencephalography (EEG) and accounts for 15–20% of all epilepsies [1], with no identifiable causes other than genetic factors [2, 3]. Results from structural imaging have reported abnormalities in the medial/orbitofrontal cortex, cingulate cortex, precuneus, and thalamus in patients with IGE [6, 8,9,10,11]. Functional connectivity (FC), which has been widely applied in fMRI and confirmed to be associated with abnormal discharges on EEG, quantifies temporal correlations between brain regions to interrogate the direct or indirect interregional interactions [2, 6, 14]. Ji et al used VMHC and reported that interhemispheric FC between the bilateral cuneus and anterior cingulate cortex increased and that between the bilateral olfactory cortex, inferior frontal gyrus, supramarginal gyrus, and temporal pole decreased in patients with generalized tonic-clonic seizures [20]

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