A rapid-onset diffusion functional MRI signal reflects neuromorphological coupling dynamics
Open accessAbstract
Functional Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function in-vivo. However, the neurovascular coupling mechanisms underlying fMRI are somewhat "distant" from neural activity. Interestingly, evidence from Intrinsic Optical Signals (IOSs) indicates that neural activity is also coupled to (sub)cellular morphological modulations. Diffusion-weighted functional MRI (dfMRI) experiments have been previously proposed to probe such neuromorphological couplings, but the underlying mechanisms have remained highly contested. Here, we provide the first direct link between in vivo ultrafast dfMRI signals upon rat forepaw stimulation and IOSs in acute slices stimulated optogenetically. We reveal a hitherto unreported rapid onset (<100 ms) dfMRI signal component which (i) agrees with fast-rising IOSs dynamics; (ii) evidences a punctate quantitative correspondence to the stimulation period; and (iii) is rather insensitive to a vascular challenge. Our findings suggest that neuromorphological coupling can be detected via dfMRI signals, auguring well for future mapping of neural activity more directly compared with blood-oxygenation-level-dependent mechanisms.
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This raises the prospect of resolving finer-scale organization, such as cortical layers or closely interwoven circuits, and of probing faster neural dynamics.
“This raises the prospect of resolving finer-scale organization, such as cortical layers or closely interwoven circuits, and of probing faster neural dynamics (Nunes et al., 2021).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Nunes et al., 2021
The Introduction and Discussion report a rapid-onset dfMRI component detected with 100 ms temporal resolution, supporting the prospect of probing faster dynamics. The Methods describe 85 µm resolution along the scanned line, and Figure 2 maps signals across cortical depth with layers I–VI marked. These findings support the prospect of finer-scale mapping, but the paper does not establish that the approach can distinguish closely interwoven circuits. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPreclinical 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 Nunes et al., 2021
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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 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).”
- Authors
- Nunes, D., Gil, R., & Shemesh, N.
- Affiliations
- Centro Champalimaud (PT)
- Corresponding author
- Shemesh, Noam
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 231
- Pages
- 117862
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W3001597959
- Cited by
- 43
- References
- 4
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 14 · 2023: 4 · 2022: 4 · 2021: 6
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- arXiv (Cornell University)
- Funders
- European Research Council (679058)
- European Regional Development Fund (LISBOA-01-0145-FEDER-022170)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- intrinsic optical signals, neurovascular coupling, optogenetic stimulation, acute brain slices
- MeSH terms
- Neurovascular Coupling, Animals, Brain, Electric Stimulation, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Time Factors, Rats, Long-Evans, Diffusion Magnetic Resonance Imaging, Mice, Rats, Optogenetics
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