Water diffusion in brain cortex closely tracks underlying neuronal activity
Open accessAbstract
Neuronal activity results in a local increase in blood flow. This concept serves as the basis for functional MRI. Still, this approach remains indirect and may fail in situations interfering with the neurovascular coupling mechanisms (drugs, anesthesia). Here we establish that water molecular diffusion is directly modulated by underlying neuronal activity using a rat forepaw stimulation model under different conditions of neuronal stimulation and neurovascular coupling. Under nitroprusside infusion, a neurovascular-coupling inhibitor, the diffusion response and local field potentials were maintained, whereas the hemodynamic response was abolished. As diffusion MRI reflects interactions of water molecules with obstacles (e.g., cell membranes), the observed changes point to a dynamic modulation of the neural tissue structure upon activation, which remains to be investigated. These findings represent a significant shift in concept from the current electrochemical and neurovascular coupling principles used for brain imaging, and open unique avenues to investigate mechanisms underlying brain function.
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Preclinical work has provided strong evidence that DfMRI responses are mechanistically distinct from BOLD responses.
“Preclinical work has provided strong evidence that DfMRI responses are mechanistically distinct from BOLD responses (Abe, Tsurugizawa, et al., 2017; Tsurugizawa et al., 2013).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Tsurugizawa et al., 2013
Preclinical work suggests that some biomechanical changes occur faster than BOLD responses, in a similar way to DfMRI.
“Preclinical work suggests that some biomechanical changes occur faster than BOLD responses, in a similar way to DfMRI (Nunes et al., 2021; Patz et al., 2019; Tsurugizawa et al., 2013).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Tsurugizawa et al., 2013
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Callow, D. D., Won, J., Pena, G. S., Jordan, L. S., Arnold-Nedimala, N. A., Kommula, Y., Nielson, K. A., & Smith, J. C. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.645258 · Cited by 27 · see citing works
Nguyen‐Duc, J., de Riedmatten, I., Spencer, A. P. C., Perot, J., Olszowy, W., & Jelescu, I. (2025) · Human Brain Mapping · doi:10.1002/hbm.70110 · Cited by 11 · see citing works
Le Bihan, D. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1858655 · Cited by 1 · see citing works
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
“Preclinical work has provided strong evidence that DfMRI responses are mechanistically distinct from BOLD responses ( Abe, Tsurugizawa, et al., 2017; Tsurugizawa et al., 2013).”
- Authors
- Tsurugizawa, T., Ciobanu, L., & Le Bihan, D.
- Affiliations
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- NeuroSpin, Bât 145, Commissariat à l’Energie Atomique-Saclay Center, 91191 Gif-sur-Yvette, France
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-06-25
- Volume
- 110
- Issue
- 28
- Pages
- 11636-11641
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3710802
- OpenAlex
- W1998588297
- Cited by
- 93
- References
- 5
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 1
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- water diffusion, neuronal activity, neurovascular coupling, diffusion MRI, local field potentials, sodium nitroprusside, hemodynamic response, cerebral cortex, forepaw stimulation, cell membrane dynamics
- MeSH terms
- Animals, Cerebral Cortex, Electric Stimulation, Male, Neurons, Water, Rats, Wistar, Rats
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