Distinct thalamic functional connectivity and volume patterns across focal epilepsies in children: A multimodal...

The thalamus is a key hub in seizure propagation, and its nuclei are emerging targets for neuromodulation. However, the contributions of individual nuclei to epileptic networks remain unclear, particularly in children, who are less studied than adults. We investigated structural and functional thalamic alterations across different pediatric focal epilepsies and their associations with clinical features and postsurgical outcomes.

We retrospectively studied children with temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and posterior quadrant epilepsy (PQE) and healthy controls. The thalamus was segmented into four nuclei groups (anterior, lateral, medial, pulvinar) using the THOMAS pipeline on T1-weighted magnetic resonance imaging (MRI) to estimate volumes. Functional connectivity was assessed with functional MRI using node strength, capturing total thalamic connectivity across the brain. We compared patients with controls and evaluated associations with hippocampal sclerosis, history of focal to bilateral tonic-clonic seizures, and postsurgical seizure freedom.

Among 136 children with focal epilepsy (81 TLE, 36 FLE, 19 PQE; mean age = 13.0 years) and 70 controls (mean age = 13.4 years), ipsilateral thalamic volume reductions were observed in the following: anterior and lateral nuclei and pulvinar in TLE, anterior and lateral nuclei in FLE, and pulvinar in PQE (Cohen d = .52-.70, all Bonferroni-corrected p < .05). In contrast, medial nuclei volume increase was associated with history of seizure generalization (partial η² = .06). Functional connectivity was bilaterally reduced across epilepsy groups (partial η² = .03), most consistently in the pulvinar (Cohen d = .25-.68). Within TLE, hippocampal sclerosis was associated with increased anterior nucleus connectivity (partial η² = .17), distinguishing it from other pathologies.

We demonstrate both shared and syndrome-specific thalamic abnormalities in pediatric focal epilepsy. Common patterns included ipsilateral thalamic volume loss, indicating cumulative disease burden, and reduced bilateral functional connectivity, particularly in the pulvinar, likely reflecting thalamocortical decoupling. These findings advance understanding of seizure networks beyond the epileptogenic zone and provide a foundation for personalized thalamic-targeted neuromodulation strategies.