Thalamocortical hodology to personalize electrical stimulation for focal epilepsy

Arianna Damiani, Sirisha Nouduri, Jonathan C. Ho, Steven Salazar, Aude Jegou, Jiahao Jay Chen, Eliza Reedy, Naoki Ikegaya, Sridevi Sarma, Thandar Aung, Elvira Pirondini and Jorge A. Gonzalez-Martinez ()
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Arianna Damiani: University of Pittsburgh
Sirisha Nouduri: University of Pittsburgh
Jonathan C. Ho: University of Pittsburgh
Steven Salazar: University of Pittsburgh
Aude Jegou: University of Pittsburgh
Jiahao Jay Chen: University of Pittsburgh
Eliza Reedy: University of Pittsburgh
Naoki Ikegaya: University of Pittsburgh
Sridevi Sarma: Johns Hopkins University
Thandar Aung: University of Pittsburgh
Elvira Pirondini: University of Pittsburgh
Jorge A. Gonzalez-Martinez: University of Pittsburgh

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Thalamic electrical stimulation offers a therapeutic approach for refractory epilepsy patients ineligibles for resective surgery. Yet, there is currently no consensus on the optimal stimulation site. We hypothesized that targeting thalamic nuclei with precise anatomical and functional connections (hodological matching) to cortical seizure onset zones (SOZs) could enhance neuromodulatory effects. Thus, we examined three subnuclei (pulvinar, anterior, and ventral intermediate/oral posterior, VIM/VOP) in 41 focal epilepsy patients. Combining neuroimaging and electrophysiology, we identified hodologically-matched targets: pulvinar for posterior-quadrant and temporal SOZs, anterior for frontotemporal, and VIM/VOP for rolandic. Analysis of 274 seizures revealed the critical role of matched nuclei in seizure termination. Stimulation of hodologically-matched (but not unmatched) nuclei immediately suppressed interictal epileptiform discharges. Finally, in 10 chronically implanted patients, matched stimulation substantially reduced seizure frequency (87.5%), compared to unmatched targets (8.3%) over time. Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in focal epilepsy.

Date: 2025
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DOI: 10.1038/s41467-025-64922-w

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