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Peer-reviewedCC BYELife

Mapping the topographic organization of the human zona incerta using diffusion MRI.

  • Roy A M Haast1,2,3
  • Jason Kai1,4
  • Alaa Taha1,5
  • Violet Liu1,6
  • Loxlan W Kasa1,5
  • Greydon Gilmore1,5,6,7
  • Maxime Guye2,3
  • Ali R Khan1,4,5,6
  • Jonathan C Lau1,5,6,7
7 affiliations
  1. 1Robarts Research Institute, Western University, London, Canada.
  2. 2Aix Marseille Univ, CNRS, CRMBM, Marseille, France.
  3. 3APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France.
  4. 4Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Canada.
  5. 5School of Biomedical Engineering, Western University, London, Canada.
  6. 6Graduate Program in Neuroscience, Western University, London, Canada.
  7. 7Division of Neurosurgery, Department of Clinical Neurological Sciences, Western University, London, Canada.
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Abstract

The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an 'immensely confusing area about which nothing can be said'. Despite the elusive nature of this structure, mounting evidence supports the role of the ZI and surrounding regions across a diverse range of brain functions and as a candidate target for neuromodulatory therapies. Using in vivo diffusion magnetic resonance imaging and data-driven connectivity, we identify a topographic organization between the ZI and neocortex. Specifically, our methods identify a rostral-caudal gradient predominantly connecting the frontopolar and ventral prefrontal cortices with the rostral ZI, and the primary sensorimotor cortices with the caudal ZI. Moreover, we demonstrate how clustering and gradient approaches build complementary evidence including facilitating the mapping of a central region of the ZI, connected with the dorsal prefrontal cortex. These results were shown to be replicable across multiple datasets and at the individual subject level, building evidence for the important role of the ZI in mediating frontal lobe-associated tasks, ranging from motor to cognitive to emotional control. Finally, we consider the impact of this topographic organization on the refinement of neuromodulatory targets. These results pave the way for an increasingly detailed understanding of ZI substructures, and considerations for in vivo targeting of the ZI for neuromodulation.

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Cite

BibTeXRIS
BibTeX
@article{haast2026mapping,
  title = {{Mapping the topographic organization of the human zona incerta using diffusion MRI.}},
  author = {Roy A M Haast and Jason Kai and Alaa Taha and Violet Liu and Loxlan W Kasa and Greydon Gilmore and Maxime Guye and Ali R Khan and Jonathan C Lau},
  journal = {ELife},
  year = {2026},
  month = oct,
  doi = {10.7554/elife.103530},
  url = {https://europepmc.org/article/MED/42912442},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Mapping the topographic organization of the human zona incerta using diffusion MRI.
AU  - Roy A M Haast
AU  - Jason Kai
AU  - Alaa Taha
AU  - Violet Liu
AU  - Loxlan W Kasa
AU  - Greydon Gilmore
AU  - Maxime Guye
AU  - Ali R Khan
AU  - Jonathan C Lau
PY  - 2026
DA  - 2026/10/23
JO  - ELife
DO  - 10.7554/elife.103530
UR  - https://europepmc.org/article/MED/42912442
AB  - The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an 'immensely confusing area about which nothing can be said'. Despite the elusive nature of this structure, mounting evidence supports the role of the ZI and surrounding regions across a diverse range of brain functions and as a candidate target for neuromodulatory therapies. Using in vivo diffusion magnetic resonance imaging and data-driven connectivity, we identify a topographic organization between the ZI and neocortex. Specifically, our methods identify a rostral-caudal gradient predominantly connecting the frontopolar and ventral prefrontal cortices with the rostral ZI, and the primary sensorimotor cortices with the caudal ZI. Moreover, we demonstrate how clustering and gradient approaches build complementary evidence including facilitating the mapping of a central region of the ZI, connected with the dorsal prefrontal cortex. These results were shown to be replicable across multiple datasets and at the individual subject level, building evidence for the important role of the ZI in mediating frontal lobe-associated tasks, ranging from motor to cognitive to emotional control. Finally, we consider the impact of this topographic organization on the refinement of neuromodulatory targets. These results pave the way for an increasingly detailed understanding of ZI substructures, and considerations for in vivo targeting of the ZI for neuromodulation.
SN  - 2050-084X
ER  -