Imaging transcriptomics of brain disorders
Open accessAbstract
Noninvasive neuroimaging is a powerful tool for quantifying diverse aspects of brain structure and function in vivo, and it has been used extensively to map the neural changes associated with various brain disorders. However, most neuroimaging techniques offer only indirect measures of underlying pathological mechanisms. The recent development of anatomically comprehensive gene expression atlases has opened new opportunities for studying the transcriptional correlates of noninvasively measured neural phenotypes, offering a rich framework for evaluating pathophysiological hypotheses and putative mechanisms. Here, we provide an overview of some fundamental methods in imaging transcriptomics and outline their application to understanding brain disorders of neurodevelopment, adulthood, and neurodegeneration. Converging evidence indicates that spatial variations in gene expression are linked to normative changes in brain structure during age-related maturation and neurodegeneration that are in part associated with cell-specific gene expression markers of gene expression. Transcriptional correlates of disorder-related neuroimaging phenotypes are also linked to transcriptionally dysregulated genes identified in ex vivo analyses of patient brains. Modeling studies demonstrate that spatial patterns of gene expression are involved in regional vulnerability to neurodegeneration and the spread of disease across the brain. This growing body of work supports the utility of transcriptional atlases in testing hypotheses about the molecular mechanism driving disease-related changes in macroscopic neuroimaging phenotypes.
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Interpreting MRI alterations in AD remains challenging because MRI contrasts reflect complex, combined contributions from cellular composition, microstructural organization, and biochemical changes rather than disease-specific processes alone, and provide only indirect measurements of underlying physiological mechanisms.
“Interpreting MRI alterations in AD remains challenging because MRI contrasts reflect complex, combined contributions from cellular composition, microstructural organization, and biochemical changes rather than disease‐specific processes alone, 26 , 79 , 80 and provide only indirect measurements of underlying physiological mechanisms. 81”
From Diffusion MRI reveals amyloid plaque–associated cellular signatures through spatial transcriptomic integration (2026) · cites this paper as [81]
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- [7]Arnatkeviciute A. Fulcher B.D. Bellgrove M.A. Fornito A. Where the genome meets the connectome: Understanding how genes shape human brain connectivity Neuroimage 244 2021 118570 34508898
Cited by
Sorted by citations
Shen, Y., Shen, Y., Wang, M., Jin, K., Yang, P., Cao, Z., Zhu, Q., Zhao, Z., Li, H., Han, L., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116073 · Cited by 10 · 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
- Arnatkeviciute, A., Fulcher, B. D., Bellgrove, M. A., & Fornito, A.
- Affiliations
- The University of Sydney (AU)
- Monash University (AU)
- Venue
- Biological Psychiatry Global Open Science
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 2
- Issue
- 4
- Pages
- 319-331
- ISSN
- 2667-1743 (ISSN-L)
- PMC
- PMC9616271
- OpenAlex
- W3206800693
- Cited by
- 113
- References
- 152
- Citations by year
- 2026: 35 · 2025: 29 · 2024: 25 · 2023: 12 · 2022: 12
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biological Psychiatry Global Open Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PsyArXiv (OSF Preprints) (submittedVersion)
- PsyArXiv (OSF Preprints) (submittedVersion, cc-by)
- Funders
- Sylvia and Charles Viertel Charitable Foundation
- National Health and Medical Research Council (1146292, 1197431)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- imaging transcriptomics, brain disorders, brain development, neurodegeneration, brain maturation
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