Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography
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Abstract
Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure-MRI-derived T1-weighted/T2-weighted (T1w/T2w) mapping-reliably indexes anatomical hierarchy, and it captures the dominant pattern of transcriptional variation across human cortex. We found hierarchical gradients in expression profiles of genes related to microcircuit function, consistent with monkey microanatomy, and implicated in neuropsychiatric disorders. Our findings identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of microscale properties may contribute to the macroscale specialization of cortical function.
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Studies integrating neuroimaging with transcriptomic data have shown that large-scale imaging features align with spatial gene-expression patterns, providing molecular context for interpreting neuroimaging findings in health and disease.
“Studies integrating neuroimaging with transcriptomic data have shown that large‐scale imaging features align with spatial gene‐expression patterns, providing molecular context for interpreting neuroimaging findings in health and disease. 82 , 83”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [83]
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Arnatkeviciute, A., Fulcher, B. D., Bellgrove, M. A., & Fornito, A. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.10.002 · Cited by 113 · see citing works
Han, X., Hu, R., Ping, X., Chen, J., Liu, J., Liu, Z., Jin, X., Gao, X., Lin, M., Zhao, Y., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71908
- Authors
- Burt, J. B., Demirtaş, M., Eckner, W. J., Navejar, N. M., Ji, J. L., Martin, W. J., Bernacchia, A., Anticevic, A., & Murray, J. D.
- Affiliations
- Yale University (US)
- Tulane University (US)
- University of Cambridge (GB)
- Corresponding author
- Murray, John D.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-08-06
- Volume
- 21
- Issue
- 9
- Pages
- 1251-1259
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6119093
- OpenAlex
- W2886680918
- Cited by
- 657
- References
- 83
- Citations by year
- 2026: 81 · 2025: 102 · 2024: 102 · 2023: 91 · 2022: 80 · 2021: 86 · 2020: 69 · 2019: 29 · 2018: 15 · 2017: 1
- FWCI
- 29.63
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (TL1TR000141, TL1TR001864)
- National Institute of Mental Health (R01MH112189, R01MH112746, R01MH108590)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- cortical hierarchy, gene expression gradients, human cortex, T1 and T2 mapping, microcircuitry, cortical specialization, non-invasive brain imaging, neuropsychiatric disorders, primate cortex
- MeSH terms
- Animals, Mental Disorders, Brain Mapping, Cerebral Cortex, Gene Expression Regulation, Humans, Interneurons, Macaca mulatta, Magnetic Resonance Imaging, Pyramidal Cells, Transcriptome, Neuroimaging
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