To assess the clinical efficacy of centromedian nucleus deep brain stimulation (CM-DBS) for drug-resistant epilepsy and explore its effects on neural activity using resting-state functional magnetic resonance imaging.

Ten patients, comprising four with Lennox–Gastaut syndrome (LGS), three with generalized epilepsy (GE) and three with multifocal epilepsy, underwent CM-DBS using thalamic segmentation for localization. Efficacy was assessed by calculating seizure frequency reduction from baseline. Two measures of resting brain activity—the amplitude of low-frequency fluctuations (ALFF), reflecting the strength of spontaneous brain signals, and regional homogeneity (ReHo), indicating the synchrony of neighboring brain regions—were analyzed to evaluate postoperative changes.

Mean seizure reduction across all patients was 61.8%. Six patients, comprising four with LGS and two with GE, demonstrated > 50% reduction in seizure frequency. ALFF decreased in the right putamen, left inferior temporal, left putamen, right supplementary motor area, right para-hippocampal gyrus, right thalamus, left superior frontal gyrus, left cerebellar vermis Ⅳ–Ⅴ, and right post cingulate gyrus. ReHo decreased in the left inferior temporal gyrus, left anterior cingulate gyrus, and right cerebellar lobe Ⅲ but increased in the left inferior occipital gyrus, left middle occipital gyrus, right middle occipital gyrus, left cuneus, and right calcarine.

Our preliminary findings in a small cohort show that CM-DBS may be effective for certain drug-resistant epilepsies, such as LGS and GE. Thalamic segmentation also enhanced visualization of target structures for clinical use. ALFF/ReHo changes reflect neural reorganization and reveal key epileptic network nodes, potentially reducing CM-DBS seizure frequency.