Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson’s disease

Thomas S. Binns, Richard M. Köhler, Jojo Vanhoecke, Meera Chikermane, Moritz Gerster, Timon Merk, Franziska Pellegrini, Johannes L. Busch, Jeroen G. V. Habets, Alessia Cavallo, Jean-Christin Beyer, Bassam Al-Fatly, Ningfei Li, Andreas Horn, Patricia Krause, Katharina Faust, Gerd-Helge Schneider, Stefan Haufe, Andrea A. Kühn and Wolf-Julian Neumann ()
Additional contact information
Thomas S. Binns: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Richard M. Köhler: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Jojo Vanhoecke: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Meera Chikermane: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Moritz Gerster: Bernstein Center for Computational Neuroscience Berlin
Timon Merk: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Franziska Pellegrini: Bernstein Center for Computational Neuroscience Berlin
Johannes L. Busch: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Jeroen G. V. Habets: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Alessia Cavallo: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Jean-Christin Beyer: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Bassam Al-Fatly: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Ningfei Li: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Andreas Horn: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Patricia Krause: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Katharina Faust: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Gerd-Helge Schneider: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Stefan Haufe: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Andrea A. Kühn: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Wolf-Julian Neumann: corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin

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

Abstract: Abstract Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson’s disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex – basal ganglia networks are unknown. To address this critical knowledge gap, we combined fully invasive neural multisite recordings in patients undergoing deep brain stimulation surgery with normative MRI-based whole-brain connectomics. Our findings demonstrate that dopamine and stimulation exert distinct mesoscale effects through modulation of local neural population activity. In contrast, at the macroscale, stimulation mimics dopamine in its suppression of excessive interregional network synchrony associated with indirect and hyperdirect cortex – basal ganglia pathways. Our results provide a better understanding of the circuit mechanisms of dopamine and deep brain stimulation, laying the foundation for advanced closed-loop neurostimulation therapies.

Date: 2025
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DOI: 10.1038/s41467-025-58825-z

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