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Cross-species lesion mapping links a midbrain circuit to vergence dysfunction.

Maximilian U Friedrich1,2,3, Anja K E Horn4, Helen Friedrich1,5

  • 1Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Boston, MA 02115, USA.

Brain : a Journal of Neurology
|December 30, 2025
PubMed
Summary

Vergence eye movements, crucial for 3D focus, are impaired in neurodegenerative diseases. This study identifies the nucleus of the posterior commissure (NPC) in the midbrain as a key region involved in vergence control.

Keywords:
brain mappingeye movementsmidbraintranslational neurosciencevergencevisuomotor

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Area of Science:

  • Neuroscience
  • Ophthalmology
  • Neurology

Background:

  • Vergence eye movements enable focus in three-dimensional space.
  • Dysfunction in vergence is observed in up to 40% of patients with neurodegenerative disorders.
  • The precise neural mechanisms underlying vergence deficits in humans remain unclear.

Purpose of the Study:

  • To elucidate the neural basis of vergence dysfunction in humans.
  • To bridge the translational gap between animal models and human clinical observations of vergence control.

Main Methods:

  • Voxel-wise lesion mapping was conducted in 66 humans and 19 monkeys with midbrain lesions.
  • Cross-species connectivity analyses were performed to map brain circuits involved in vergence.

Main Results:

  • Vergence dysfunction was causally linked to a midbrain region rostral to the superior colliculus, centered on the nucleus of the posterior commissure (NPC).
  • A conserved brain circuit connecting the NPC to visual pretectum and premotor hubs was identified across species.

Conclusions:

  • The nucleus of the posterior commissure (NPC) plays a critical role in human vergence control.
  • This research provides a neuroanatomical foundation for understanding vergence dysfunction in neurodegenerative diseases.
  • Lesion mapping effectively connects animal model findings with human clinical data.