Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes

Abstract

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of "self-limited focal epilepsies." In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 ± 11.46. Two independent general linear model models were created for each patient based on the effect of interest: "individual CTS" in model 1 and "CTS density" in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical-subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood-oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks.

Keywords: BOLD; CECTS; centrotemporal spikes; cognition; epileptic discharges frequency; language network.

Figure 1

(A) Group-level individual centrotemporal spike (CTS) model (p < 0.001, 10 voxels extent). The functional maps are warped to the PALS-B12 atlas in caret (lateral view) for right (Rh) and left (Lh) hemisphere and to flat template. (B) Group-level density CTS model (p < 0.001, 10 voxels extent). The functional maps are warped to the PALS-B12 atlas in Caret (lateral view) for right (Rh) and left (Lh) hemisphere and to flat template. For localization purposes, functional results on the left hemisphere were plotted and compared against Brodmann areas of language areas (BA44, BA45, and BA22) indicated by the black numbers. In addition, to show the subcortical findings, BOLD changes have been overlaid into the canonical T1 0.5 mm image (coronal, axial, and sagittal slices) as implemented in FSL (FMRIB Software Library). L, left; R, right. The white lines on the PALS-B12 atlas and flat template show the central and sylvian fissure surface landmarks as implemented in Caret. The yellow-red color identifies positive BOLD changes. Negative BOLD changes were not observed. See text for details.

Figure 2

(A) The overlaid of individual CTS model (green color) and CTS density model (red color) is displayed onto the flat template as implemented by Caret for left (Lh) and right hemisphere (Rh). (B) The main effect contrast derived from group-level density CTS > baseline analysis was exclusively masked by the mask contrast “individual CTS > baseline,” at a threshold of p < 0.05, uncorrected for multiple comparison. See text for details. Clusters of activations are overlaid into the canonical T1 0.5-mm image (coronal, axial, and sagittal slices) as implemented in FSL (FMRIB Software Library). R, right; L, left.

Figure 3

Whole-brain correlation analysis between CTS density-related BOLD changes and disease's duration (A) and age at fMRI (B) are warped to the PALS-B12 atlas in caret (lateral and mesial view) for right (Rh) and left (Lh) hemisphere and to flat template. See text for details. For localization purposes, functional results were plotted and compared against Brodmann areas indicated by the black numbers. The white lines on the PALS-B12 atlas and flat template show the central and sylvian fissure surface landmarks as implemented in Caret. The yellow-red color identifies the positive correlations, the light-blue color the negative correlations.