Interpreting the BOLD Signal
Abstract
▪ Abstract The development of functional magnetic resonance imaging (fMRI) has brought together a broad community of scientists interested in measuring the neural basis of the human mind. Because fMRI signals are an indirect measure of neural activity, interpreting these signals to make deductions about the nervous system requires some understanding of the signaling mechanisms. We describe our current understanding of the causal relationships between neural activity and the blood-oxygen-level-dependent (BOLD) signal, and we review how these analyses have challenged some basic assumptions that have guided neuroscience. We conclude with a discussion of how to use the BOLD signal to make inferences about the neural signal.
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The BOLD response does not always track underlying neuronal signaling faithfully and can diverge from activation-driven oxygen metabolism in some regions or conditions.
“Because the BOLD response depends on local changes in cerebral blood flow, blood volume, and oxygenation, it does not always track underlying neuronal signaling faithfully and can diverge from activation-driven oxygen metabolism in some regions or conditions (Epp et al., 2026; Logothetis & Wandell, 2004; Sirotin & Das, 2009).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Logothetis & Wandell, 2004
Gray matter has denser vasculature than white matter.
“the gray matter is more densely vascularized than the white matter (132).”
From Electrophysiological source imaging: A noninvasive window to brain dynamics (2018) · cites this paper as [132]
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A collaborative resource platform for non-human primate neuroimaging
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Winton-Brown, T., Schmidt, A., Roiser, J. P., Howes, O. D., Egerton, A., Fusar-Poli, P., Bunzeck, N., Grace, A. A., Duzel, E., Kapur, S., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.174 · Cited by 51 · see citing works
Combining fMRI and behavioral measures to examine the process of human learning
Karuza, E. A., Emberson, L. L., & Aslin, R. N. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.09.012 · Cited by 50 · see citing works
Brain network dynamics during spontaneous strategy shifts and incremental task optimization
Allegra, M., Seyed-Allaei, S., Schuck, N. W., Amati, D., Laio, A., & Reverberi, C. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116854 · Cited by 27 · see citing works
Spatial dynamics of masked picture repetition effects
Eddy, M. D., Schnyer, D., Schmid, A., & Holcomb, P. J. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.10.031 · Cited by 22 · see citing works
Midbrain fMRI: Applications, Limitations and Challenges
Düzel, E., Guitart-Masip, M., Maass, A., Hämmerer, D., Betts, M. J., Speck, O., Weiskopf, N., & Kanowski, M. (2015) · Biological Magnetic Resonance · doi:10.1007/978-1-4899-7591-1_20 · Cited by 16 · see citing works
Fetal functional imaging portrays heterogeneous development of emerging human brain networks
Jakab, A., Schwartz, E., Kasprian, G., Gruber, G. M., Prayer, D., Schöpf, V., & Langs, G. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00852 · Cited by 10 · see citing works
Theriault (n.d.) · doi:10.31234/osf.io/pkzr8 · Cited by 51 · see citing works
Hart, M. G., Romero-Garcia, R., Price, S. J., Santarius, T., & Suckling, J. (2020) · World Neurosurgery · doi:10.1016/j.wneu.2020.03.116 · Cited by 7 · 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
“…on local changes in cerebral blood flow, blood volume, and oxygenation, it does not always track underlying neuronal signaling faithfully and can diverge from activation-driven oxygen metabolism in some regions or conditions (Epp et al., 2026; Logothetis & Wandell, 2004; Sirotin & Das, 2009).”
- Authors
- Logothetis, N. K., & Wandell, B. A.
- Affiliations
- Max Planck Institute for Biological Cybernetics (DE)
- Stanford University (US)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2004-03-01
- Volume
- 66
- Issue
- 1
- Pages
- 735-769
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2164121465
- Cited by
- 1,568
- References
- 161
- Citations by year
- 2026: 38 · 2025: 51 · 2024: 45 · 2023: 39 · 2022: 52 · 2021: 75 · 2020: 57 · 2019: 51 · 2018: 120 · 2017: 65 · 2016: 81 · 2015: 89 · 2014: 84 · 2013: 88 · 2012: 86
- FWCI
- 11.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Eye Institute (R01EY003164)
- 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
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- BOLD signal, functional MRI, neuronal activity, hemodynamic response, blood oxygenation, signal interpretation
- MeSH terms
- Animals, Brain, Brain Mapping, Cerebrovascular Circulation, Electrophysiology, Humans, Magnetic Resonance Imaging, Models, Neurological, Oxygen
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