Biophysical and Physiological Origins of Blood Oxygenation Level-Dependent fMRI Signals
Open accessAbstract
After its discovery in 1990, blood oxygenation level-dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) has been widely used to map brain activation in humans and animals. Since fMRI relies on signal changes induced by neural activity, its signal source can be complex and is also dependent on imaging parameters and techniques. In this review, we identify and describe the origins of BOLD fMRI signals, including the topics of (1) effects of spin density, volume fraction, inflow, perfusion, and susceptibility as potential contributors to BOLD fMRI, (2) intravascular and extravascular contributions to conventional gradient-echo and spin-echo BOLD fMRI, (3) spatial specificity of hemodynamic-based fMRI related to vascular architecture and intrinsic hemodynamic responses, (4) BOLD signal contributions from functional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of O 2 utilization (CMRO 2 ), (5) dynamic responses of BOLD, CBF, CMRO 2 , and arterial and venous CBV, (6) potential sources of initial BOLD dips, poststimulus BOLD undershoots, and prolonged negative BOLD fMRI signals, (7) dependence of stimulus-evoked BOLD signals on baseline physiology, and (8) basis of resting-state BOLD fluctuations. These discussions are highly relevant to interpreting BOLD fMRI signals as physiological means.
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The origin of fMRI is complex and incompletely understood.
“The origin of fMRI is rather complex and incompletely understood (118).”
From Electrophysiological source imaging: A noninvasive window to brain dynamics (2018) · cites this paper as [118]
The mechanism of neurovascular coupling is not fully understood, but understanding it is essential for interpreting fMRI.
“The mechanism of neurovascular coupling is incompletely understood but essential to interpretation of fMRI (114, 118).”
From Electrophysiological source imaging: A noninvasive window to brain dynamics (2018) · cites this paper as [118]
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Functional quantitative susceptibility mapping (fQSM)
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Neurovascular Coupling and Decoupling in the Cortex during Voluntary Locomotion
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Vazquez, A. L., Fukuda, M., Crowley, J. C., & Kim, S.-G. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht147 · Cited by 86 · see citing works
Self-citationShim, H., Jung, W. B., Schlegel, F., Lee, J., Kim, S., Lee, J., & Kim, S. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.04.062 · Cited by 86 · see citing works
Self-citationRole of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance
Lee, J.-Y., You, T., Lee, C.-H., Im, G. H., Seo, H., Woo, C., & Kim, S. (2022) · Current Biology · doi:10.1016/j.cub.2022.04.090 · Cited by 85 · see citing works
Self-citationAltered Cerebral Blood Flow Covariance Network in Schizophrenia
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Oxygen imaging of hypoxic pockets in the mouse cerebral cortex
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Neuroimaging for psychotherapy research: current trends.
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“Deoxygenated hemoglobin has a magnetic property that can decrease nearby MRI signals (such as from protons of water molecules in blood vessels; Kim & Ogawa, 2012).”
BackgroundAmygdala subnuclei response and connectivity during emotional processing
Hrybouski, S., Aghamohammadi-Sereshki, A., Madan, C., Shafer, A. T., Baron, C., Seres, P., Beaulieu, C., Olsen, F., & Malykhin, N. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.056 · Cited by 87 · see citing works
Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI
Moon, H. S., Jiang, H., Vo, T. T., Jung, W. B., Vazquez, A. L., & Kim, S. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab068 · Cited by 80 · see citing works
Self-citationBrain activity is not only for thinking
Laumann, T. O., & Snyder, A. Z. (2021) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2021.04.002 · Cited by 76 · see citing works
Neurovascular uncoupling in resting state fMRI demonstrated in patients with primary brain gliomas
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Existence of Initial Dip for BCI: An Illusion or Reality
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Osmanski, B.-F., Martin, C., Montaldo, G., Lanièce, P., Pain, F., Tanter, M., & Gurden, H. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.03.054 · Cited by 74 · see citing works
The Spectral Diversity of Resting-State Fluctuations in the Human Brain
Kalcher, K., Boubela, R. N., Huf, W., Bartova, L., Kronnerwetter, C., Derntl, B., Pezawas, L., Peter Filzmoser, A., Našel, C., & Moser, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093375 · Cited by 73 · see citing works
Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience
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Engineering the human blood-brain barrier in vitro
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A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state
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Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome
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Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS
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Lamina-dependent calibrated BOLD response in human primary motor cortex
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Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow
Jung, W. B., Im, G. H., Jiang, H., & Kim, S. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023265118 · Cited by 69 · see citing works
Self-citationLayer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb
Poplawsky, A. J., Fukuda, M., Murphy, M. C., & Kim, S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1015-15.2015 · Cited by 69 · see citing works
Self-citationPlacental MRI and its application to fetal intervention
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Giannoni, L., Lange, F., & Tachtsidis, I. (2018) · Journal of Optics · doi:10.1088/2040-8986/aab3a6 · Cited by 66 · see citing works
The aging brain and cerebrovascular reactivity
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Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection
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Dopamine-Induced Dissociation of BOLD and Neural Activity in Macaque Visual Cortex
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Simultaneous GCaMP6-based fiber photometry and fMRI in rats
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Mouse BOLD fMRI at ultrahigh field detects somatosensory networks including thalamic nuclei
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Disrutpted resting-state functional architecture of the brain after 45-day simulated microgravity
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The Coordinate-Based Meta-Analysis of Neuroimaging Data
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MB-SWIFT functional MRI during deep brain stimulation in rats
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- Authors
- Kim, S.-G., & Ogawa, S.
- Affiliations
- University of Pittsburgh (US)
- Tohoku Fukushi University (JP)
- Corresponding author
- Kim, Seong-Gi
- ORCID
- Kim, Seong-Gi
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2012-03-07
- Volume
- 32
- Issue
- 7
- Pages
- 1188-1206
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3390806
- OpenAlex
- W2102673550
- Cited by
- 547
- References
- 150
- Citations by year
- 2026: 41 · 2025: 35 · 2024: 45 · 2023: 26 · 2022: 32 · 2021: 46 · 2020: 43 · 2019: 42 · 2018: 39 · 2017: 37 · 2016: 41 · 2015: 39 · 2014: 50 · 2013: 26 · 2012: 3
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 44589, R01NS044589)
- National Institute of Biomedical Imaging and Bioengineering (EB-003375, EB 003324, R01EB003324, R01EB003375)
- 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, spin density, blood volume fraction, inflow effects, perfusion, susceptibility, hemodynamic response, cerebral blood flow, cerebral blood volume, cerebral oxygen consumption, vascular architecture
- MeSH terms
- Animals, Brain, Brain Mapping, Cerebrovascular Circulation, Hemodynamics, Humans, Magnetic Resonance Imaging, Oxygen Consumption
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