Functional Connectivity of the Anterior Nucleus of the Thalamus in Pediatric Focal Epilepsy

Abstract

Objective: Whilst stimulation of the anterior nucleus of the thalamus has shown efficacy for reducing seizure frequency in adults, alterations in thalamic connectivity have not been explored in children. We tested the hypotheses that (a) the anterior thalamus has increased functional connectivity in children with focal epilepsy, and (b) this alteration in the connectome is a persistent effect of the disease rather than due to transient epileptiform activity. Methods: Data from 35 children (7-18 years) with focal, drug-resistant epilepsy and 20 healthy children (7-17 years) were analyzed. All subjects underwent functional magnetic resonance imaging (fMRI) whilst resting and were simultaneously monitored with scalp electroencephalography (EEG). The fMRI timeseries were extracted for each Automated Anatomical Labeling brain region and thalamic subregion. Graph theory metrics [degree (DC) and eigenvector (EC) centrality] were used to summarize the connectivity profile of the ipsilateral thalamus, and its thalamic parcellations. The effect of interictal epileptiform discharges (IEDs) captured on EEG was used to determine their effect on DC and EC. Results: DC was significantly higher in the anterior nucleus (p = 0.04) of the thalamus ipsilateral to the epileptogenic zone in children with epilepsy compared to controls. On exploratory analyses, we similarly found a higher DC in the lateral dorsal nucleus (p = 0.02), but not any other thalamic subregion. No differences in EC measures were found between patients and controls. We did not find any significant difference in DC or EC in any thalamic subregion when comparing the results of children with epilepsy before, and after the removal of the effects of IEDs. Conclusions: Our data suggest that the anterior and lateral dorsal nuclei of the thalamus are more highly functionally connected in children with poorly controlled focal epilepsy. We did not detect a convincing change in thalamic connectivity caused by transient epileptiform activity, suggesting that it represents a persistent alteration to network dynamics.

Keywords: childhood epilepsies; connectivity; deep brain stimulation; electroencephaloagraphy; epilepsy; focal epilepsies; functional magnetic resonance imaging; thalamus.

Figure 1

Imaging analysis pipeline. (A) Pre-processing pipeline. (B) Timeseries extraction. (C) Demonstration of the correction method for interictal epileptiform discharges (IEDs) in the anterior nucleus of the thalamus for patients 13 (one spike type) as detailed in Table 1. (D) Functional network analysis.

Figure 2

Degree centrality of the anterior thalamic subregion ipsilateral to the epileptogenic zone (EZ). The lines represent controls (blue), patients before (red) and after (green) correction for interictal epileptiform discharges (IEDs). The left graphs show the full range of network densities from 0 to 100%. The dotted box shows the range selected for statistical analysis and shown in the right graph.

Figure 3

Area under the curve (AUC) for the degree centrality of the anterior thalamic subregion ipsilateral to the epileptogenic zone (EZ). The violin plot (28) demonstrates the distributions of the AUC for degree centrality in patients before (red) and after (green) interictal epileptiform discharges (IEDs) and controls (blue). The clear dot shows the median.