Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Frederic L. W. V. J. Schaper*, Birgit R. Plantinga, Albert J. Colon, G. Louis Wagner, Paul Boon, Nadia Blom, Erik D. Gommer, Govert Hoogland, Linda Ackermans, Rob P. W. Rouhl, Yasin Temel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.

OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MIT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.

RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r' = 0.24, P = .01) and is -30% smaller (P = .015) in responders than in nonresponders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.

CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

Original languageEnglish
Pages (from-to)602-610
Number of pages9
Issue number3
Publication statusPublished - Sept 2020


  • Neuromodulation
  • DRE
  • Drug-resistant epilepsy
  • Thalamus
  • Mammillothalamic tract
  • White matter stimulation
  • MRI

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