Thalamocortical structural connectivity in children with focal epilepsy: a diffusion MRI, case-control study

Objectives Determining patient-specific thalamic connectivity alterations may be an important step towards personalized surgical and neuromodulation strategies, but no data are available to support this concept in pediatric cohorts. This study investigated thalamocortical structural connectivity profiles in children with focal-onset epilepsy of different seizure onset zones. Methods This neuroimaging, case-control study compared structural connectivity of four thalamic nuclei (anteroventral (AV), centromedian (CM), mediodorsal (MDPf) and pulvinar (PUL)) between 81 children who underwent surgery for focal-onset epilepsy (median age=12.2 years) and 63 controls (median age=12.8 years). Using preoperative 3-tesla diffusion MRI, brain (Lausanne) and thalamic (THOMAS) parcellations combined with tractography generated structural connectomes based on streamline counts. Connectivity strength of each thalamic nucleus was calculated by summing the weights of each connecting brain region. Results Patients had higher structural connectivity strengths of the thalamic nuclei than controls (effect size (partial eta-squared=0.146; p<0.001), differentially involving nucleus regions, but there was no overall difference in nucleus volumes (partial eta-squared<0.000; p=0.968). When comparing patient groups defined by seizure onset zones, it emerged that reduced AV connectivity strength was specific to the hippocampal sclerosis group, whereas CM, MDPf and PUL connectivity was similarly high in all the patient groups, including those with frontal or temporal lobe epilepsy. Patients who were seizure free after surgery had a lower ipsilateral and a higher contralateral connectivity strength (partial eta-squared=0.109; p=0.006) and volumes (partial eta-squared=0.073; p=0.025) of thalamic nuclei compared to those who were not. Significance This study provides unique data suggesting that different pediatric focal epilepsies have distinct structural thalamocortical connectivity and volumetric profiles. The structural connectivity and volumetric asymmetries of the thalami have an association with postoperative seizure freedom. More studies are required to further understand the thalamic connectivity signatures that may have implications for precision surgical planning and neuromodulation targeting for focal-onset epilepsy.