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

Overview

1. Robarts Research Institute, Western University, London, Canada
2. Aix Marseille Univ, CNRS, CRMBM, Marseille, France
3. APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France
4. Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Canada
5. School of Biomedical Engineering, Western University, London, Canada
6. Graduate Program in Neuroscience, Western University, London, Canada
7. Division of Neurosurgery, Department of Clinical Neurological Sciences, Western University, London, Canada

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

• github.com/ataha24/zona-clusters, at github.com; found in the references
• humanconnectome.org/study/hcp-young-adult, at Human Connectome Project; found in “Data availability”

Data availability

The non-clinical data used in this study are available as part of the publicly available Human Connectome Project S1200 release (humanconnectome.org/study/hcp-young-adult). Anonymized stimulated volumes and clinical scores are available at github.com/ataha24/zona-clusters, copy archived at Taha and Haast, 2024. The raw clinical data contain protected health information and cannot be made publicly available because of restrictions protecting patient privacy and confidentiality. Requests for access should be directed to the corresponding author. Any access granted will be subject to applicable ethical and institutional approvals. Analysis was performed using a combination of publicly available toolboxes: Connectome Workbench v2.0 (Marcus et al., 2011), BrainSpace v0.1.10 (Vos de Wael et al., 2020), NeuroSynth v0.3.8 (Yarkoni et al., 2011), neuromaps v0.0.3 (Markello et al., 2022), BrainStat v0.3.2 (Larivière et al., 2023), and custom Python code available at the code repository. A full list of installed Python packages is listed in the repository as well.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 25 October 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 9 authors, 1 keyword, 6 MeSH terms, 5 funders, 112 references.

Cite

This paper

Haast, R. A., Kai, J., Taha, A., Liu, V., Kasa, L. W., Gilmore, G., Guye, M., Khan, A. R., & Lau, J. C. (2026). Mapping the topographic organization of the human zona incerta using diffusion MRI. eLife, 14, RP103530. https://doi.org/10.7554/elife.103530

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