Cited by 272Advanced Neuroimaging Techniques and ApplicationsAdvanced MRI Techniques and ApplicationsNMR spectroscopy and applications

Direct and fast detection of neuronal activation in the human brain with diffusion MRI

Le Bihan, Denis, Urayama, Shin-ichi, Aso, Toshihiko, Hanakawa, Takashi, Fukuyama, Hidenao·2006·Proceedings of the National Academy of Sciences

Abstract

Using MRI, we found that a slowly diffusing water pool was expanding (1.7 ± 0.3%) upon activation on the human visual cortex at the detriment of a faster diffusing pool. The time course of this water phase transition preceded the activation-triggered vascular response detected by usual functional MRI by several seconds. The observed changes in water diffusion likely reflect early biophysical events that take place in the activated cells, such as cell swelling and membrane expansion. Although the exact mechanisms remain to clarify, access to such an early and direct physiological marker of cortical activation with MRI will provide opportunities for functional neuroimaging of the human brain.

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Crossref · 10.1073/pnas.0600644103

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  • Diffusion MRI was shown to detect brain activation through transient decreases in ADC, suggesting sensitivity to intrinsic microstructural changes in addition to possible vascular effects.

    “A major conceptual shift occurred in the early 2000s when diffusion MRI was shown to detect brain activation through transient decreases in ADC, suggesting sensitivity to intrinsic microstructural changes in addition to possible vascular effects (Fig. 6) (Darquié et al., 2001; Le Bihan et al., 2006).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Le Bihan et al., 2006

    The Results show that diffusion MRI detected activation-related changes in the human visual cortex, and the Conclusion links them to likely biophysical changes in activated cells. But the Results explicitly caution that the signal increase cannot be converted into a drop in a single diffusion coefficient; the authors instead favor a shift from a fast- to a slow-diffusing water phase. Thus, describing this paper's finding as a transient decrease in ADC overstates what it establishes. (LLM, conf=0.89)

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  • T2-related effects are largely independent of b-value, so that, when echo time is matched, their contributions can be substantially reduced or eliminated by calculating an ADC or sADC derived from two b-values.

    “T2-related effects (which are weaker than T2*-weighted BOLD) are largely independent of b-value, so that, when echo time is matched, their contributions can be substantially reduced or eliminated by calculating an ADC or, better, sADC derived from two b-values (Aso et al., 2009; de Riedmatten, Spencer, Olszowy, et al., 2025; Le Bihan et al., 2006; Spencer et al., 2025).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Le Bihan et al., 2006

    The ‘Origin of the Observed MRI Signal Changes’ section reports small R2/R2*-related BOLD variations at very low b-values and says diffusion sensitization reduces the vascular BOLD component. It does not say T2-related effects are largely b-value independent or that calculating an ADC or sADC from two matched-echo-time b-values removes them; the reduction it describes comes from diffusion sensitization, not that calculation. No page numbers are available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • Visual stimulation-induced stiffness increase mirrors activation-related ADC and sADC decreases observed with DfMRI.

    “mirroring activation-related ADC and sADC decreases observed with DfMRI (Le Bihan et al., 2006).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Le Bihan et al., 2006

    The Results report a decrease in water diffusion during visual activation, supporting the general DfMRI comparison. But they attribute the signal change to expansion of the slow-diffusion pool and state that changes in the pools’ diffusion coefficients could not explain it; our copy does not establish the claimed sADC decrease. The stiffness comparison is the citing authors’ framing, not a finding attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • IVIM effects are mostly visible at low b-values and can be eliminated using higher b-values.

    “There are also IVIM effects (see above) that are mostly visible at low b-values and can be eliminated using higher b-values (Le Bihan et al., 2006).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Le Bihan et al., 2006

  • In human visual cortex, diffusion changes preceded the BOLD response and were closely time locked to stimulation.

    “In human visual cortex, these diffusion changes preceded the BOLD response and were closely time locked to stimulation (Darquié et al., 2001; Kohno et al., 2009; Le Bihan et al., 2006).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Le Bihan et al., 2006

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Authors
Le Bihan, D., Urayama, S.-I., Aso, T., Hanakawa, T., & Fukuyama, H.
Affiliations
  • Human Brain Research Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;
  • Kyoto University (JP)
Venue
Proceedings of the National Academy of Sciences
Published
2006-05-23
Volume
103
Issue
21
Pages
8263-8268
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2134330663
Cited by
272
References
54
Citations by year
2026: 4 · 2025: 15 · 2024: 20 · 2023: 10 · 2022: 9 · 2021: 17 · 2020: 9 · 2019: 8 · 2018: 16 · 2017: 14 · 2016: 13 · 2015: 18 · 2014: 15 · 2013: 15 · 2012: 13
FWCI
13.21
Type
journal article
Language
en
Open access
closed
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
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
  • Physical Sciences › Physics and Astronomy › Nuclear and High Energy Physics › NMR spectroscopy and applications
Keywords
neuronal activation, diffusion MRI, water diffusion, visual cortex, cortical activation, vascular response, cell swelling, membrane expansion, functional neuroimaging
MeSH terms
Adult, Biophysics, Brain, Brain Mapping, Cell Membrane, Female, Humans, Magnetic Resonance Imaging, Male, Neurons, Time Factors, Visual Cortex, Models, Statistical, Diffusion Magnetic Resonance Imaging

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