A Causal Brain Network Related to Seizure Response after Centromedian Deep Brain Stimulation
Abstract number :
1.245
Submission category :
3. Neurophysiology / 3E. Brain Stimulation
Year :
2025
Submission ID :
995
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Karim Mithani, MD, MEng – Hospital for Sick Children
Hrishikesh Suresh, MD – Hospital for Sick Children
Yousof Alrumayyan, MD – Hospital for Sick Children
Simeo Wong, MHSc(BME), PhD – SickKids Research Institute
Sebastian Coleman, PhD – SickKids Research Institute
Puneet Jain, MD DM – Hospital for Sick Children
George Ibrahim, MD, PhD – Hospital for Sick Children
Rationale: The centromedian nuclei (CM) of the thalamus are key hubs in the mammalian brain, with extensive projections supporting various neurocognitive functions. Deep brain stimulation (DBS) targeting the CM is a promising therapy for drug-resistant epilepsy, supported by animal studies showing cortical desynchronization via CM stimulation. However, its effects on human neural circuits remain poorly understood. We combined stereoelectroencephalography (SEEG), ambulatory local field potentials (LFPs), and normative structural/metabolic imaging to characterize circuits associated with CM stimulation.
Methods: We studied 39 children with drug-resistant epilepsy: 22 with SEEG including thalamic coverage (CM-SEEG) and 17 who underwent CM-DBS with ≥ 1-year follow-up. To define a causal stimulation network, we analyzed single-pulse stimulation (SPES) data from 12 CM-SEEG participants (CM-SPES cohort). Using normative structural connectomics in the CM-DBS cohort, we then identified circuits linked to seizure reduction and compared these to the CM-SPES-defined network (“CM-stim network”). We also explored seizure propagation through the CM-stim network, examining: (1) whether ictal CM activity predicted DBS response via LFPs from sensing devices, and (2) whether CM-stim network engagement preceded ictal CM involvement in SEEG.
Results: CM-SPES evoked activity in a widespread network involving sensorimotor and association areas cortically, and the dorsal striatum subcortically, defining the “CM-stim network” (FWER p < 0.05). Clustering of evoked waveforms revealed sensorimotor, cingulo-opercular, and posterior associative subnetworks. Normative metabolic imaging showed enrichment in acetylcholine (r = 0.22, p = 0.021) and norepinephrine (r = 0.22, p = 0.047). In the CM-DBS cohort, connectivity between the stimulation volume and sensorimotor cortices and locus coeruleus predicted better outcomes. This DBS-associated network overlapped substantially with the CM-stim network and was similarly enriched in acetylcholine (r = 0.31, p = 0.012) and norepinephrine transporters (r = 0.25, p = 0.044). Ambulatory LFPs revealed that ictal CM activity was associated with seizure reduction (p < 0.001). In turn, ictal activity in the CM-stim network preceded CM involvement in the majoriy of participants.
Neurophysiology