New Hope for Drug-Resistant Epilepsy Through Centromedian Nucleus Stimulation

Around one-third of the 50 million people living with epilepsy worldwide do not respond to anti-seizure medications, leaving them with limited treatment options. Surgical removal of the seizure-causing region can sometimes help, but it is not viable when seizures originate from multiple or unclear brain regions.

Deep brain stimulation (DBS) has emerged as a promising alternative for these patients. DBS involves implanting electrodes that deliver controlled electrical impulses to specific brain regions to help control seizures. While stimulation of the anterior nucleus of the thalamus is already approved for epilepsy treatment in Europe and Canada, researchers are now increasingly focused on another promising target: the centromedian nucleus (CM).

The Centromedian Nucleus: A Challenging but Promising Target

The CM has extensive cortical and subcortical connections, making it a strong candidate for controlling generalized and frontal lobe seizures, including those seen in conditions such as Lennox–Gastaut syndrome. However, its small size, deep location, and proximity to other thalamic nuclei make accurate targeting challenging with standard imaging techniques.

Misplaced electrodes can reduce the effectiveness of DBS and increase surgical risks. This technical difficulty has slowed the widespread adoption of CM-DBS as a standard treatment approach.

Innovative Techniques to Improve CM Targeting

In a recent review published in Brain Network Disorders (Volume 1, Issue 2, March 9, 2025), a research team led by Dr. Cristina Virgina Torres Díaz from University Hospital La Princesa, Madrid, in collaboration with the University Medical Center of the Johannes Gutenberg University Mainz, examined cutting-edge methods to enhance CM targeting during DBS procedures.

“Our primary goal was to reduce targeting errors and expand the clinical viability of CM-DBS,” says Dr. Torres Díaz, corresponding author of the study. “By integrating advanced imaging and neurophysiology, we can more confidently localize the CM, especially in patients with complex anatomy or structural abnormalities.”

Advanced Imaging: MP2RAGE and Other MRI-Based Tools

The review highlights the use of an MRI sequence called magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE), which provides high-resolution brain imaging. MP2RAGE improves contrast between the CM and surrounding thalamic structures, enabling clearer anatomical identification. When combined with 3D brain atlases and image gradient analysis, it enhances CM visualization.

Other promising MRI-based techniques include quantitative susceptibility mapping (QSM) and EDGE-MICRA (edge-enhancing gradient echo with multi-image co-registration and averaging), which may further refine CM delineation.

Neurophysiological Guidance Through Microelectrode Recordings

The authors also discussed intraoperative microelectrode recordings (MER), which record electrical activity from deep brain structures during surgery. MER can distinguish the CM from nearby nuclei based on its unique neural firing patterns.

MER data from previous studies show that the CM exhibits distinctive ‘tonic activity’ and ‘lower spike rates’ compared to neighboring nuclei like the ventral lateral nucleus, making it a useful neurophysiological marker during electrode implantation.

Mapping Brain Pathways with DTI Tractography

Diffusion tensor imaging (DTI) tractography is another approach explored in the review. This technique maps brain pathways and helps guide stimulation to circuits linked with seizure control.

Studies have shown that optimal stimulation sites are closely aligned with fiber tracts connecting the CM to the brainstem, cerebellum, sensorimotor cortex, and supplementary motor area. Patients whose electrodes targeted these pathways often experienced a 50% or greater reduction in seizure frequency.

“Through the review of our own patient series, we found that patients who responded most favorably to CM-DBS had strong structural and functional links between the stimulation site and specific brain networks involved in motor regulation and arousal,” Dr. Torres Díaz explained. “This highlights the importance of targeting not just a nucleus, but the circuits it controls.”

Towards Personalized DBS Therapies for Epilepsy

This review offers a comprehensive roadmap for implementing CM-DBS in patients with drug-resistant epilepsy. By combining high-resolution imaging, intraoperative electrophysiological mapping, and connectivity analysis, surgical teams can better tailor electrode placement to each patient’s unique brain anatomy and seizure network.

“As diagnostic tools advance and improve our understanding of brain networks, CM-DBS could offer life-changing results for patients once deemed untreatable,” concludes Dr. Torres Díaz. “Precision targeting is not just a technical achievement; it is a path to renewed hope for people with the most challenging forms of epilepsy.”

Summary

One-third of epilepsy patients are resistant to anti-seizure drugs, with limited treatment options.
Deep brain stimulation (DBS) is emerging as an alternative, targeting seizure epicenters using electrical impulses.
The centromedian nucleus (CM) is a promising DBS target but challenging to locate accurately.
A review highlights advanced techniques to improve CM targeting:
- MP2RAGE, QSM, EDGE-MICRA for clearer MRI-based imaging
- Microelectrode recordings (MER) to identify unique neural activity of the CM
- DTI tractography to map relevant brain circuits for optimal stimulation
Accurate targeting of the CM correlates with significant seizure reduction.
Combining these approaches can personalize DBS therapy and improve surgical outcomes.

Precision CM-DBS could transform care for patients with drug-resistant epilepsy.

Original Publication
Authors: Guillermo J. Bazarra Castro, Gabriel González-Escamilla, Carlos Martínez Macho, Alejandra Madero Pohlen, Adrián Martin Segura, Amelia Álvarez-Sala, Enrique Barbero Pablos, Sergiu Groppa, Jose A. Fernández-Alén and Cristina Virgina Torres Díaz.
Journal: Brain Network Disorders
DOI: 10.1016/j.bnd.2024.11.002
Method of Research: Literature review
Subject of Research: Not applicable
Article Title: Targeting the centromedian nucleus of the thalamus for epilepsy
Article Publication Date: 26-Jun-2025
COI Statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.