Neurophysiological investigation of the basis of the fMRI signal
Abstract
Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.
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Local field potentials and tissue oxygen response, which directly contribute to the generation of the BOLD signals, were preserved at both low and high frequencies.
“Importantly, local field potentials and tissue oxygen response, which directly contribute to the generation of the BOLD signals (Logothetis et al., 2001), were preserved at both frequencies.”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Logothetis et al., 2001
fMRI signals in secondary visual areas can serve as a rough surrogate of V1 output.
“Although the electrophysiological activity in V1 could not be directly assessed in our experiment, based on the literature (Logothetis et al., 2001) we can obtain a rough surrogate of V1 output by evaluating fMRI signals in the secondary visual areas, which receive input directly from V1.”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Logothetis et al., 2001
During simultaneous recordings with sensory stimulation, the BOLD response correlates more with LFP than MUA.
“When recorded simultaneously during sensory stimulation, the BOLD response is more correlated with LFP than MUA (129, 130).”
From Electrophysiological source imaging: A noninvasive window to brain dynamics (2018) · cites this paper as [129]
The fMRI signal primarily originates from synaptic activity in gray matter rather than from spiking activity.
“Increasing evidence suggests that the primary source of fMRI is synaptic activity, rather than spiking activity, in the gray matter (129, 130).”
From Electrophysiological source imaging: A noninvasive window to brain dynamics (2018) · cites this paper as [129]
The BOLD response is thought to be generated by local excitatory synaptic activity, leading to precisely localised changes in blood flow in response to the release of glutamate.
“The BOLD response is thought to be generated by local excitatory synaptic activity (Logothetis et al., 2001), leading to precisely localised changes in blood flow in response to the release of glutamate (Attwell and Iadecola, 2002).”
From The social brain in adolescence: evidence from functional magnetic resonance imaging and behavioural studies (2011) · cites this paper as Logothetis et al., 2001
The fMRI BOLD signal reflects in part the input into an area and intrinsic computations within it.
“Under the view that the fMRI BOLD signal reflects in part the input into an area and intrinsic computations within it (Logothetis et al., 2001)”
From States versus Rewards: Dissociable Neural Prediction Error Signals Underlying Model-Based and Model-Free Reinforcement Learning (2010) · cites this paper as Logothetis et al., 2001
The association between fast gamma oscillations and whole-brain vascular hyperactivity has also been observed under anesthesia in previous EEG-fMRI and intrinsic optical signal (IOS)-fMRI studies.
“which was also observed under anesthesia in previous EEG-fMRI and intrinsic optical signal (IOS)-fMRI studies35,36.”
From Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep (2018) · cites this paper as [35]
Gradient echo T2*-weighted echo-planar images sensitive to the BOLD contrast were acquired as an index of local increases in synaptic activity.
“Gradient echo T2*-weighted echo-planar images (EPIs) sensitive to the BOLD contrast were acquired as an index of local increases in synaptic activity (48)”
From Threatening a rubber hand that you feel is yours elicits a cortical anxiety response. (2007) · cites this paper as [48]
fMRI is one of the most common and reliable methods of measuring brain function at decent spatial and temporal resolutions, but because it is an indirect measure of brain activity, interpretation of gene effects is limited.
“fMRI is one the most common and reliable methods of measuring brain function at decent spatial and temporal resolutions, but given that it is an indirect measure of brain activity, reflecting a paradigm related change in metabolic consumption (Logothetis, Pauls et al. 2001), interpretation of gene effects is limited.”
From Developmental imaging genetics: Linking dopamine function to adolescent behavior (2014) · cites this paper as Logothetis, Pauls et al. 2001
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- Authors
- Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A.
- Affiliations
- Max Planck Institute for Biological Cybernetics (DE)
- Max Planck Society (DE)
- Corresponding author
- Logothetis, Nikos K.
- ORCID
- Logothetis, Nikos K.
- Venue
- Nature
- Published
- 2001-07-12
- Volume
- 412
- Issue
- 6843
- Pages
- 150-157
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2114104729
- Cited by
- 6,542
- References
- 50
- Citations by year
- 2026: 126 · 2025: 211 · 2024: 193 · 2023: 198 · 2022: 237 · 2021: 281 · 2020: 239 · 2019: 292 · 2018: 227 · 2017: 295 · 2016: 240 · 2015: 282 · 2014: 288 · 2013: 287 · 2012: 318
- FWCI
- 179.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- 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, local field potentials, intracortical recording, neurovascular coupling, hemodynamic response, visual cortex, linear systems analysis, impulse response
- MeSH terms
- Action Potentials, Animals, Electrodes, Electrophysiology, Hemodynamics, Macaca mulatta, Magnetic Resonance Imaging, Synaptic Transmission, Neurons
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