Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson’s disease
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.
Authors
- Timon Merk (ORCID: https://orcid.org/0000-0003-3011-2612)
- Andrea A. Kühn (ORCID: https://orcid.org/0000-0002-4134-9060)
- Johannes L. Busch (ORCID: https://orcid.org/0000-0002-1280-5928)
- Jeroen Habets (ORCID: https://orcid.org/0000-0002-1015-093X)
- Franziska Pellegrini (ORCID: https://orcid.org/0000-0001-9769-1597)
- Meera Chikermane (ORCID: https://orcid.org/0000-0003-1800-1346)
- Thomas S. Binns
- Katharina Faust (ORCID: https://orcid.org/0000-0001-9969-0141)
- Bassam Al‐Fatly (ORCID: https://orcid.org/0000-0003-0067-6177)
- Wolf‐Julian Neumann (ORCID: https://orcid.org/0000-0002-6758-9708)
- Moritz Gerster (ORCID: https://orcid.org/0000-0001-9343-6986)
- Patricia Krause (ORCID: https://orcid.org/0000-0001-9063-0556)
- Richard M. Köhler (ORCID: https://orcid.org/0000-0002-5219-1289)
- Ningfei Li (ORCID: https://orcid.org/0000-0003-3315-3591)
- Gerd‐Helge Schneider (ORCID: https://orcid.org/0000-0002-1301-2938)
- Stefan Haufe (ORCID: https://orcid.org/0000-0003-1470-9195)
- Jonathan Vanhoecke (ORCID: https://orcid.org/0000-0002-9857-1519)
- Alessia Cavallo (ORCID: https://orcid.org/0000-0003-1717-1378)
- Andreas Horn (ORCID: https://orcid.org/0000-0003-2130-6853)
- J. Beyer
Institutions
- Brigham and Women's Hospital (US)
- Physikalisch-Technische Bundesanstalt (DE)
- Harvard University (US)
- Humboldt-Universität zu Berlin (DE)
- Massachusetts General Hospital (US)
- Circuit Therapeutics (United States) (US)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Bernstein Center for Computational Neuroscience Berlin (DE)
- Technische Universität Berlin (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1038/s41467-025-58825-z
- Citations
- 33
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 45.85
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Berlin Institute of Health