Tracking neuronal fiber pathways in the living human brain
Open accessAbstract
Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109–110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.
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The first tractography demonstrations offered a three-dimensional, noninvasive picture of large-scale anatomical connections in living humans.
“The first demonstrations (Basser et al., 2000; Conturo et al., 1999; Jones et al., 1999; Mori et al., 1999; Poupon et al., 2000) immediately captured the imagination of the field because they offered something previously unattainable in living humans: a three-dimensional, noninvasive picture of large-scale anatomical connections (Fig. 4).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Conturo et al., 1999
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Drakesmith, M., Caeyenberghs, K., Dutt, A., Lewis, G., David, A. S., & Jones, D. K. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.05.011 · Cited by 157 · see citing works
The role of diffusion MRI in neuroscience
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Visualizing the neural bases of a disconnection syndrome with diffusion tensor imaging
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Validation of tractography: Comparison with manganese tracing
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40 Years of diffusion MRI in the brain: From history to emerging frontiers
Le Bihan, D. (2026) · Imaging Neuroscience · doi:10.1162/imag.a.1365
“The first demonstrations ( Basser et al., 2000; Conturo et al., 1999; Jones et al., 1999; Mori et al., 1999; Poupon et al., 2000) immediately captured the imagination of the field because they offered some-thing previously unattainable in living humans: a three-dimensional, noninvasive picture of…”
- Authors
- Conturo, T. E., Lori, N. F., Cull, T. S., Akbudak, E., Snyder, A. Z., Shimony, J. S., McKinstry, R. C., Burton, H., & Raichle, M. E.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-08-31
- Volume
- 96
- Issue
- 18
- Pages
- 10422-10427
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC17904
- OpenAlex
- W2170596158
- Cited by
- 1,774
- References
- 1
- Citations by year
- 2026: 14 · 2025: 32 · 2024: 25 · 2023: 32 · 2022: 30 · 2021: 48 · 2020: 59 · 2019: 63 · 2018: 37 · 2017: 49 · 2016: 56 · 2015: 74 · 2014: 88 · 2013: 103 · 2012: 82
- FWCI
- 38.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dana Foundation
- National Institutes of Health (5p01ns006833-25, NS06833)
- National Institute of Neurological Disorders and Stroke (P01 NS06833, P50NS006833)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- diffusion MRI, white matter connectivity, corpus callosum, retinotopy, functional MRI
- MeSH terms
- Brain, Brain Mapping, Humans, Magnetic Resonance Imaging, Nerve Fibers, Neural Pathways, Neurons
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