Cross-species lesion mapping links a midbrain circuit to vergence dysfunction
The ability to shift focus within three-dimensional space depends on vergence eye movements, which are impaired in ≤40% of individuals with neurodegenerative disorders. Although foundational studies in monkeys have identified neural correlates of vergence in the midbrain, a translational gap persists, leaving the neural basis of vergence dysfunction in humans poorly understood. Through voxel-wise analyses in 66 humans and 19 monkeys with midbrain lesions, we link vergence dysfunction causally to a region rostral to the superior colliculus and centred on the nucleus of the posterior commissure (NPC). Connectivity analyses across species identified a brain circuit linking the NPC to the visual pretectum and midbrain premotor hubs, regions capable of integrating the visual input and motor output necessary for vergence control. Collectively, these findings provide a neuroanatomical basis for vergence dysfunction and demonstrate how lesion mapping can bridge fundamental insights from animal models with clinical observations in humans.
Authors
- Vallabh E. Das (ORCID: https://orcid.org/0000-0003-2507-6573)
- Ümit S. Mayadali
- Konstantin Butenko (ORCID: https://orcid.org/0000-0002-4509-4624)
- Janet C. Rucker (ORCID: https://orcid.org/0000-0002-0397-0999)
- Martin M. Reich (ORCID: https://orcid.org/0000-0001-9115-5136)
- David S. Zee (ORCID: https://orcid.org/0000-0003-3909-2494)
- Maximilian Friedrich (ORCID: https://orcid.org/0000-0002-3695-1268)
- Shawn Hiew (ORCID: https://orcid.org/0009-0004-9785-5597)
- Chi Wang Ip (ORCID: https://orcid.org/0000-0003-0484-385X)
- Robert L. Peach (ORCID: https://orcid.org/0000-0002-8738-5825)
- Helen Friedrich
- Andreas Zwergal (ORCID: https://orcid.org/0000-0002-3839-8398)
- Hazem Eldebakey
- Michael Fox (ORCID: https://orcid.org/0000-0001-8848-6399)
- Jens Volkmann (ORCID: https://orcid.org/0000-0002-9570-593X)
- Johannes Hartig (ORCID: https://orcid.org/0000-0002-3669-8856)
- Barbara Changizi
- Daniel Zeller
- Marianne Dieterich
- Anja K E Horn
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- University of Würzburg (DE)
- Johns Hopkins Medicine (US)
- LMU Klinikum (DE)
- NYU Langone Health (US)
- Circuit Therapeutics (United States) (US)
- Universitätsklinikum Würzburg (DE)
- German Center for Lung Research (DE)
- University of Houston (US)
- Imperial College London (GB)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Brain
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1093/brain/awaf316
- Primary Topic
- Vestibular and auditory disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00