Cortical evoked potentials from deep brain stimulation of the superolateral medial forebrain bundle: An exploratory study

Clin Neurophysiol. 2026 Oct 29;194:2112451. doi: 10.1016/j.clinph.2026.2112451. Online ahead of print.

ABSTRACT

OBJECTIVE: Deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB-DBS) has shown promising therapeutic effects in treatment-resistant depression and obsessive-compulsive disorder. Here, we explore for the first time the electrophysiological connectivity between the stimulation target and cortical sites in humans.

METHODS: Electrophysiological responses to single slMFB-DBS pulses were mapped in 7 patients using epidural electrocorticography (ECoG; n = 4) or high-density electroencephalography (EEG; n = 3) over 11 sessions. Electrooculography (EOG) was simultaneously recorded, given that oculomotor side-effects are common after slMFB-DBS.

RESULTS: Cortical evoked potentials were observed in 5 of 7 patients, with consistent latencies across modalities and prefrontal EEG topographies. In one patient, screening a broad parameter space demonstrated clear modulation of ECoG responses by DBS parameters. EOG activity consistent with oculomotor nerve co-activation was present in 6 of 7 patients, yet differed in timing and morphology from cortical responses.

CONCLUSION: This work shows effective connectivity between the slMFB-DBS target and the prefrontal cortex via ECoG and EEG, complementing existing structural connectivity data.

SIGNIFICANCE: This is the first exploratory study demonstrating electrophysiological connectivity between the slMFB-DBS target and the prefrontal cortex in humans, opening the door to future studies which should systematically address their robustness and suitability for objective, biomarker-guided slMFB-DBS.

PMID:42982009 | DOI:10.1016/j.clinph.2026.2112451