Neuromodulation of the Centromedian Nucleus of the Thalamus for the Treatment of Generalized Drug-Resistant Epilepsy: Novel Insights Into the Targeting and the Anti-Seizure MechanismFroma Tractographic Study

INTRODUCTION: Neuromodulation of the centromedian nucleus (CM) has been investigated with promising results for the treatment of generalized drug-resistant epilepsy (gDRE). Recent evidence suggests a more clinically beneficial “sweet-spot” corresponding to the thalamic area between the antero-lateral CM and the posterior subdivision of the ventrolateral nucleus. However, it is unclear if this region can be considered a new target or still a subcomponent of CM. METHODS: We analyzed diffusion and structural MRI scans from 9 DRE patients, who underwent CM-stimulation surgery. CM masks from the THOMAS atlas and 2 spherical ROIs from the MNI coordinates of the sweet-spot and the cold-spot in Warren et al. 2022 were used as seed regions for probabilistic tractography (FSL software). 42 cortical and subcortical areas were selected as target regions and divided in 5 groups: sensorimotor, associative, basal ganglia, infratentorial and limbic structures. Mean structural connectivity was calculated using descriptive statistics and statistical significance was tested with a standard t-test. Statistical comparison among the 3 seed regions was conducted using ANOVA. RESULTS: For each seed, statistically significant (p < 0.05) connections were found for all the 5 groups. When comparing the 3 seeds, the CM and the cold-spot had stronger connections with the postcentral and the superior temporal cortices, the brainstem, the caudate and the amygdala; the sweet-spot with the precentral and the superior frontal cortices, the cerebellum, the putamen and the nucleus accumbens. However, no statistically significant differences resulted among the 3 seeds. CONCLUSIONS: CM has widespread connections with both cortical and subcortical structures. The sweet-spot seems to correspond to the parvocellular part of CM on the border with the ventrolateral nucleus. CM connections with frontal and prefrontal areas and the cerebellum may underlie the beneficial effect against generalized seizures.