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Rethinking the centrality of brain areas in understanding functional organization

Nature Neuroscience volume 29, pages 267–278 (2026) Cite this article

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Abstract

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive functions appear to be implemented in a broadly distributed manner, whereas others appear to obey organizations that have little relationship to brain areas, including distributed networks and functional gradients. We conclude by suggesting a set of guiding principles for performing systems and cognitive neuroscience without the intellectual foundation provided by arealization.

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Fig. 1: Cytoarchitecture supports a more nuanced view of brain areas.
The alternative text for this image may have been generated using AI.
Fig. 2: Data summarizing the responses of nearly 300,000 neurons from mice performing a learning/choice task, generated by the International Brain Laboratory62.
The alternative text for this image may have been generated using AI.
Fig. 3: Illustration of several organizing principles of function in addition to area.
The alternative text for this image may have been generated using AI.
Fig. 4: Functional organization in the brain that ignores areal boundaries.
The alternative text for this image may have been generated using AI.
Fig. 5: Illustration of how population neural coding principles can support computations often supported by arealization.
The alternative text for this image may have been generated using AI.

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Acknowledgements

This work was supported by the McNair Foundation and by NIH R01MH125377, R01DA038615 and R01MH129439 (B.Y.H.), R01MH118257 (S.R.H.) and Ministry of Food and Drug Safety of South Korea RS-2024-0033312 (S.B.M.Y.).

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  1. These authors contributed equally: Benjamin Yost Hayden, Sarah R. Heilbronner, Seng Bum Michael Yoo.

Authors and Affiliations

  1. Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

    Benjamin Yost Hayden, Sarah R. Heilbronner & Seng Bum Michael Yoo

  2. Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA

    Benjamin Yost Hayden, Sarah R. Heilbronner & Seng Bum Michael Yoo

  3. Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea

    Seng Bum Michael Yoo

  4. Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, South Korea

    Seng Bum Michael Yoo

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Hayden, B.Y., Heilbronner, S.R. & Yoo, S.B.M. Rethinking the centrality of brain areas in understanding functional organization. Nat Neurosci 29, 267–278 (2026). https://doi.org/10.1038/s41593-025-02166-z

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