Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures

Abstract

Structural and functional abnormalities in the thalamocortical network in primary generalized epilepsies or mesial temporal lobe epilepsy have recently been identified by voxel-wise analyses of neuroimaging. However, evidence is needed regarding the profiles of the thalamocortical network in patients with secondarily generalized seizures from focal neocortical sources. We used high-resolution T1-weighted, diffusion-tensor and resting-state functional MR imaging (rs-fMRI) to examine 16 patients with secondarily generalized extratemporal lobe seizures and 16 healthy controls. All the patients were medically effective and MRI-negative. Using whole brain voxel-based morphometry (VBM) to compare the patients with the normal controls, we observed significantly decreased gray matter (GM) density in the thalamus and 3 frontal gyri and significantly reduced white matter (WM) fractional anisotropy (FA) in the bilateral anterior corona radiata of the patients. Alterations in the thalamocortical functional connectivity with different cortices were identified by the rs-fMRI analysis seeding of the whole thalamus. The prefrontal gyri with the greatest functional connectivity were also traced by seeding a sub-thalamic region that is demarcated in an atlas, in which the thalamic parcellation is based on the WM connectivity to the cortices. This sub-thalamic region anatomically contains the mediodorsal thalamic nucleus where, concordantly, there was a significant decrease in thalamic GM density in the VBM study. In contrast to the negative correlation between the disease duration and reduced thalamic densities and subcortical FA values, the strength of the functional thalamocortical connectivity had a paradoxical correlation. Our results conclusively indicate that generalized seizures with a focal cortical source are associated with structural and functional alterations in the thalamocortical network.

Keywords: Fractional anisotropy; Generalized seizure; Gray matter density; Thalamocortical network.

Fig. 1

Statistical parametric maps superimposed on standard T1 MRI template images show a significant GM density reduction in the bilateral thalami in patients compared to control (AlphaSim correction, p < 0.01, minimum cluster size threshold of 16 voxels). The color bar represents the t-score.

Fig. 2

Statistic parametric maps superimposed on the international consortium of brain mapping template for FA map show the clusters of significant FA value reduction (AlphaSim correction, p < 0.01, minimum cluster size threshold of 16 voxels). The color bar shows the t-score and the magnitude of the significant difference.

Fig. 3

Between-group comparisons of thalamocortical FC. A Significant increases of thalamocortical FC in the left inferior temporal gyrus, right inferior frontal gyrus, left middle frontal gyrus, and right superior frontal gyrus and decreases in the right insula and right midcingulate area are shown in patients compared to controls. B The thalamus parcellation atlas composed of a green sub-region 4, which is responsible for the prefrontal cortical area. Significantly increased FC between sub-thalamic region 4 and the right inferior frontal gyrus and right superior frontal gyrus and decreases in the right inferior frontal gyrus and right insula are shown in patients compared to controls. The color bar represents the t-score.

Fig. 4

Relationship between GM density, FA values, functional connectivity strength and the duration of epilepsy. A The GM density of the thalamus was negatively correlated with the disease duration. B The FA values of the bilateral anterior corona radiata were negatively correlated with the disease duration. C The disease duration was positively correlated with the functional connectivity strength of the left middle frontal gyrus. D The functional connectivity strength of the left middle frontal gyrus was negatively correlated with the FA values of the bilateral anterior corona radiata. The circles represent patients with left frontotemporal seizures. The triangles represent patients with right/bilateral frontopolar seizures. The squares represent the others.