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Cited by 437Advanced MRI Techniques and ApplicationsOptical Imaging and Spectroscopy TechniquesFunctional Brain Connectivity Studies

Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity

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Sirotin, Yevgeniy B., Das, Aniruddha·2009·Nature
DOI 10.1038/nature07664PMC PMC2705195
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Abstract

Haemodynamic signals underlying functional brain imaging (for example, functional magnetic resonance imaging (fMRI)) are assumed to reflect metabolic demand generated by local neuronal activity, with equal increases in haemodynamic signal implying equal increases in the underlying neuronal activity. Few studies have compared neuronal and haemodynamic signals in alert animals to test for this assumed correspondence. Here we present evidence that brings this assumption into question. Using a dual-wavelength optical imaging technique that independently measures cerebral blood volume and oxygenation, continuously, in alert behaving monkeys, we find two distinct components to the haemodynamic signal in the alert animals' primary visual cortex (V1). One component is reliably predictable from neuronal responses generated by visual input. The other component-of almost comparable strength-is a hitherto unknown signal that entrains to task structure independently of visual input or of standard neural predictors of haemodynamics. This latter component shows predictive timing, with increases of cerebral blood volume in anticipation of trial onsets even in darkness. This trial-locked haemodynamic signal could be due to an accompanying V1 arterial pumping mechanism, closely matched in time, with peaks of arterial dilation entrained to predicted trial onsets. These findings (tested in two animals) challenge the current understanding of the link between brain haemodynamics and local neuronal activity. They also suggest the existence of a novel preparatory mechanism in the brain that brings additional arterial blood to cortex in anticipation of expected tasks.

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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 Sirotin & Das, 2009

    The paper’s Abstract reports that trial-related blood-volume and oxygenation signals in the primary visual cortex of two alert monkeys were poorly predicted by concurrent neuronal recordings. This supports the warning that haemodynamic signals need not faithfully track local neuronal activity. The study used optical imaging, however; it did not directly measure BOLD responses or demonstrate divergence from activation-driven oxygen metabolism. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Because part of its nonvascular mechanism, DfMRI may be less blurred by vascular architecture supplying multiple functional units, as observed with BOLD.

    “Because part of its nonvascular mechanism, it may be less blurred by vascular architecture supplying multiple functional units, as observed with BOLD (Sirotin & Das, 2009).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Sirotin & Das, 2009

    The paper’s Abstract reports anticipatory haemodynamic signals in monkey visual cortex and questions whether haemodynamic signals uniformly reflect local neuronal activity. Searches for DfMRI, vascular blurring, spatial resolution, and vessels supplying multiple functional units found no passage addressing the claimed comparison with BOLD. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • BOLD fMRI is vulnerable to pathology, anesthesia, and vasoactive drugs, while vascular anatomy and delayed hemodynamic responses constrain spatial specificity and temporal resolution.

    “It is also vulnerable to pathology, anesthesia, and vasoactive drugs, while vascular anatomy and delayed hemodynamic responses constrain spatial specificity and temporal resolution (Sirotin & Das, 2009; Turner, 2002).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Sirotin & Das, 2009

    The paper’s Abstract questions whether haemodynamic signals reliably reflect local neuronal activity, but does not address the limitations attributed to it here. Searches for pathology, anesthesia, vasoactive drugs, vascular anatomy, spatial specificity, and delayed responses did not find passages establishing the claimed effects on BOLD fMRI. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 26

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Authors
Sirotin, Y. B., & Das, A.
Affiliations
  • Columbia University (US)
  • New York State Psychiatric Institute (US)
Corresponding author
Das, Aniruddha
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2009-01
Volume
457
Issue
7228
Pages
475-479
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature07664
PMC
PMC2705195
OpenAlex
W2148331740
Cited by
437
References
2
Citations by year
2026: 7 · 2025: 9 · 2024: 14 · 2023: 15 · 2022: 21 · 2021: 11 · 2020: 27 · 2019: 13 · 2018: 8 · 2017: 19 · 2016: 24 · 2015: 28 · 2014: 30 · 2013: 28 · 2012: 28
FWCI
46.09
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
National Eye Institute (R01EY013759)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Keywords
BOLD signal, neuronal activity, primary visual cortex, cerebral blood volume, cerebral oxygenation, monkeys
MeSH terms
Acoustic Stimulation, Animals, Auditory Cortex, Brain Mapping, Cerebrovascular Circulation, Darkness, Fixation, Ocular, Hemodynamics, Macaca mulatta, Magnetic Resonance Imaging, Models, Neurological, Neurons, Oxygen Consumption, Photic Stimulation, Time Factors, Visual Cortex, Reproducibility of Results

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