Altered thalamic connectivity patterns in pediatric temporal lobe epilepsy: A gradient mapping study

Abstract

Objective: The thalamus participates in seizure propagation and is a target for neuromodulation in epilepsy. Although thalamic connectivity changes have been reported in adults with temporal lobe epilepsy (TLE), pediatric TLE is distinct, characterized by greater etiological diversity and impact on brain maturation. This study applied a novel gradient mapping technique to investigate whole-brain thalamic connectivity patterns in children with TLE.

Methods: Sixty-two children with TLE (ages 5-18) and 61 controls (ages 6-20) underwent a covert verb generation task functional magnetic resonance imaging (fMRI). Thalamic connectivity gradients were computed to capture primary axes of variation and compared between groups. Associations between thalamic gradients and focal to bilateral tonic-clonic seizure (FBTCS) history, hippocampal sclerosis, and post-surgical seizure outcomes were examined.

Results: Two primary thalamic connectivity gradients were identified across both groups. The first (G1) followed an anterior-posterior axis, with anterior thalamic regions connected to prefrontal cortices and basal ganglia, and posterior regions to somatosensory and visual cortices. The second (G2) spanned a superior-inferior axis, with superior thalamus connected to dorsal frontal and parietal cortices, and inferior regions to ventral areas such as the inferior temporal lobe. No differences were found in neocortical connectivity; however, subcortical alterations were observed. Both gradients showed increased thalamic connectivity to the bilateral basal ganglia and mesial temporal regions in TLE compared to controls. Increased anterior thalamic-basal ganglia connectivity along G1 was more pronounced in children with a FBTCS history. Hippocampal sclerosis was associated with reduced bilateral thalamo-hippocampal connectivity along both gradients, and along G2, stronger ipsilateral thalamo-hippocampal connectivity predicted better post-surgical seizure control.

Significance: This study identified two key thalamic connectivity patterns in pediatric TLE, revealing heightened thalamic connectivity to mesial temporal regions and to the basal ganglia. Findings suggest an adaptive inhibitory basal ganglia output on thalamo-cortical seizure transmission and the potential predictive value of thalamo-hippocampal connectivity for surgical outcomes.

Keywords: epilepsy; functional connectivity; gradients; pediatric; thalamus.