Multiscale reorganization of brain and behavior under large-scale electrical perturbation

Kreuzer, S.; Dukart, J.; Hansen, J. Y.; Nguyen, H. K.; Bentsch, M.; Zieger, S.; Sakreida, K.; Baghai, T. C.; Nothdurfter, C.; Groezinger, M.; Draganski, B.; Misic, B.; Bzdok, D.; Eickhoff, S. B.; Poeppl, T. B.

doi:10.64898/2026.03.23.713593

bioRxiv · 10.64898/2026.03.23.713593

Multiscale reorganization of brain and behavior under large-scale electrical perturbation

Kreuzer, S.·Dukart, J.·Hansen, J. Y.·Nguyen, H. K.·Bentsch, M.·Zieger, S.·Sakreida, K.·Baghai, T. C.·Nothdurfter, C.·Groezinger, M.·Draganski, B.·Misic, B.·Bzdok, D.·Eickhoff, S. B.·Poeppl, T. B.

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Abstract

Large-scale electrical perturbation of the human brain provides a unique model for understanding how multiscale biological constraints shape behaviorally relevant reorganization. Here, we integrate longitudinal neuroimaging coordinates from 148 experiments ({approx}2,300 subjects) with normative connectomics, chemoarchitecture, intrinsic electrophysiology, and transcriptomics to identify cross-scale principles governing human brain reconfiguration under strong perturbation. Convergent hubs of structural and functional plasticity embed within default-mode and salience systems and show complementary coupling to visual networks, linking perturbation-induced change to large-scale circuits supporting affective regulation, memory, interoception, and psychosis-relevant processes. These macroscopic patterns align with intrinsic cortical dynamics and chemoarchitectural gradients dominated by 5-HT1A receptors, with additional contributions from D2, -opioid and GABAA systems, and are enriched for astrocytic and microglial gene expression, implicating glial plasticity in systems-level reorganization. Finally, in a separate intervention dataset, regularized statistical-learning models demonstrate that this multiscale signature tracks behaviorally relevant symptom change specifically under strong electrical perturbation. Together, these results outline general organizing principles linking molecular, cellular and network-level constraints to human behavioral adaptation, providing a computational framework for understanding how large-scale perturbations reshape brain systems across levels of biological organization.

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Kreuzer, S., Dukart, J., Hansen, J. Y., Nguyen, H. K., Bentsch, M., Zieger, S., Sakreida, K., Baghai, T. C., Nothdurfter, C., Groezinger, M., Draganski, B., Misic, B., Bzdok, D., Eickhoff, S. B., Poeppl, T. B.. 2026-03-25. Multiscale reorganization of brain and behavior under large-scale electrical perturbation. https://doi.org/10.64898/2026.03.23.713593

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