Aberrant basal ganglia-thalamo-cortical network topology in juvenile absence epilepsy: A resting-state EEG-fMRI study

Abstract

Purpose: The underlying pathophysiology of juvenile absence epilepsy (JAE) is unclear. Since cortical and subcortical brain regions are thought to be altered in genetic generalized epilepsy, the present study examined the resting-state functional network topology of the same regions in JAE.

Methods: Electroencephalography and functional magnetic resonance imaging (EEG-fMRI) were performed on 18 JAE patients and 28 healthy controls (HCs). The topology of functional networks was analyzed using the graph-theoretic method. Both global and nodal network parameters were calculated, and parameters differing significantly between the two groups were correlated with clinical variables.

Results: Both JAE patients and HCs had small-world functional network topological architectures. However, JAE patients showed higher values for the global parameters of clustering coefficient (Cp) and normalized characteristic path length (Lambda). At the nodal level, patients exhibited greater centrality at widespread cortices, including the left superior parietal gyrus, right superior temporal gyrus, right orbital part of middle frontal gyrus and bilateral supplementary motor area. Conversely, patients showed decreased nodal centrality predominantly in the limbic network, left thalamus and right caudate nucleus. Degree centrality in the right hippocampus and betweenness centrality in the right caudate nucleus positively correlated with epilepsy duration.

Conclusion: The global functional network of JAE shows small-world properties, but tends to be regular with higher segregation and lower integration. Regions in the basal ganglia-thalamo-cortical network have aberrant nodal centrality. The hippocampus and caudate nucleus may reorganize as epilepsy progresses. Our findings indicate the pathogenesis and compensatory mechanisms to seizure attacks and cognitive deficits of JAE.

Keywords: Genetic generalized epilepsy; Graph theory; Juvenile absence epilepsy; Network reorganization; Resting-state functional MRI.