Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain

Abstract

Our objective was to evaluate the brain regions showing increased and decreased metabolism in patients at the time of generalized bursts of epileptic discharges in order to understand their mechanism of generation and effect on brain function. By recording the electroencephalogram during the functional MRI, changes in the blood oxygenation level-dependent signal were obtained in response to epileptic discharges observed in the electroencephalogram of 15 patients with idiopathic generalized epilepsy. A group analysis was performed to determine the regions of positive (activation) and negative (deactivation) blood oxygenation level-dependent responses that were common to the patients. Activations were found bilaterally and symmetrically in the thalamus, mesial midfrontal region, insulae, and midline and bilateral cerebellum and on the borders of the lateral ventricles. Deactivations were bilateral and symmetrical in the anterior frontal and parietal regions and in the posterior cingulate gyri and were seen in the left posterior temporal region. Activations in thalamus and midfrontal regions confirm known involvement of these regions in the generation or spread of generalized epileptic discharges. Involvement of the insulae in generalized discharges had not previously been described. Cerebellar activation is not believed to reflect the generation of discharges. Deactivations in frontal and parietal regions remarkably followed the pattern of the default state of brain function. Thalamocortical activation and suspension of the default state may combine to cause the actual state of reduced responsiveness observed in patients during spike-and-wave discharges. This brief lapse of responsiveness may therefore not result only from the epileptic discharge but also from its effect on normal brain function.

Fig. 1.

Significant positive BOLD response observed from the group analysis of 15 IGE patients obtained by using the HRF peaking at5s(A-C)andat7s(D), corrected P < 0.05 for spatial extent. Functional data are superimposed on the average brain template of the Montreal Neurological Institute. (A) Axial view showing activation in the cerebellum (cluster 5) and inferior part of the insula (cluster 4). (B) Axial view showing the largest cluster (cluster 4) and involving the thalami and insulae. (C) Sagittal interhemispheric view showing an activation along a wide band of mesial frontal cortex (cluster 6) and within the cerebellum (cluster 5). (D) Sagittal view of the right hemisphere 2 cm away from the midline showing an activation within the ventricles (cluster 7). This activation was bilateral and followed the ventricles until the trigone.

Fig. 2.

Significant negative BOLD response observed from the group analysis of 15 IGE patients obtained by using HRF peaking at 9 s, corrected P < 0.05 for spatial extent. (A) Axial view showing bilateral deactivations in mesial and lateral anterior frontal areas (cluster 10) and in the left posterior temporal area (cluster 13). (B) Axial view 1 cm higher than A and showing deactivations in frontal regions (cluster 10), in parietal areas (clusters 11 and 12), and in the posterior cingulate gyrus (cluster 11). (C) Axial view 2 cm above B and showing the same frontal and parietal clusters. (D) Sagittal view of the right hemisphere 1 cm away from the midline and showing a deactivation within the mesial prefrontal area (cluster 10) and the posterior cingulate gyrus (cluster 11).