Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects

Cyr, C.; Holubecki, A. M.; Shi, L.; Lakshman, M.; Salvo, J. J.; Anderson, N. L.; Kragel, J. E.; Lurie, S. M.; Voss, J.; Kokkinos, V.; Rosenow, J.; Schuele, S. U.; Johnson, E. L.; Zelano, C.; Braga, R. M.

doi:10.1101/2025.07.31.667730

bioRxiv · 10.1101/2025.07.31.667730

Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects

Cyr, C.·Holubecki, A. M.·Shi, L.·Lakshman, M.·Salvo, J. J.·Anderson, N. L.·Kragel, J. E.·Lurie, S. M.·Voss, J.·Kokkinos, V.·Rosenow, J.·Schuele, S. U.·Johnson, E. L.·Zelano, C.·Braga, R. M.

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Abstract

Intracranial electrical stimulation (ES) is routinely used therapeutically, diagnostically, and to provide causal evidence in neuroscience studies. However, our understanding of the brain network-level effects of ES remains limited. We applied precision functional mapping (PFM), based on functional magnetic resonance imaging (fMRI), to define large-scale networks within individual epilepsy patients. We show that single-pulse electrical stimulation (SPES) and high-frequency electrical stimulation (HFES) are more likely to evoke within-network responses and elicit network-related behavioral effects, respectively, when applied near to a PFM-defined network region. Network-level effects were more likely when stimulating sites in white matter, in close proximity to the targeted network, and within a region predominantly occupied by the targeted network. Further, network-specific modulation may be achievable by applying lower current intensities at these sites. Our findings support that modulation of specific networks is achievable by targeting ES to a functional anatomic "sweet spot" that can be identified using PFM.

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Cyr, C., Holubecki, A. M., Shi, L., Lakshman, M., Salvo, J. J., Anderson, N. L., Kragel, J. E., Lurie, S. M., Voss, J., Kokkinos, V., Rosenow, J., Schuele, S. U., Johnson, E. L., Zelano, C., Braga, R. M.. 2025-08-03. Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects. https://doi.org/10.1101/2025.07.31.667730

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