Glutamatergic function in the resting awake human brain is supported by uniformly high oxidative energy
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Rodent (13)C magnetic resonance spectroscopy studies show that glutamatergic signaling requires high oxidative energy in the awake resting state and allowed calibration of functional magnetic resonance imaging (fMRI) signal in terms of energy relative to the resting energy. Here, we derived energy used for glutamatergic signaling in the awake resting human. We analyzed human data of electroencephalography (EEG), positron emission tomography (PET) maps of oxygen (CMR(O2)) and glucose (CMR(glc)) utilization, and calibrated fMRI from a variety of experimental conditions. CMR(glc) and EEG in the visual cortex were tightly coupled over several conditions, showing that the oxidative demand for signaling was four times greater than the demand for nonsignaling events in the awake state. Variations of CMR(O2) and CMR(glc) from gray-matter regions and networks were within ±10% of means, suggesting that most areas required similar energy for ubiquitously high resting activity. Human calibrated fMRI results suggest that changes of fMRI signal in cognitive studies contribute at most ±10% CMR(O2) changes from rest. The PET data of sleep, vegetative state, and anesthesia show metabolic reductions from rest, uniformly >20% across, indicating no region is selectively reduced when consciousness is lost. Future clinical investigations will benefit from using quantitative metabolic measures.
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The best estimate for the oxygen-glucose index (OGI) in resting gray matter is around ∼5.5.
“The best estimates for the oxygen–glucose index (OGI; OGI = CMRO2/CMRglc) in the resting brain is around ∼5.5 in gray matter (Clarke and Sokoloff, 1994; Hyder et al., 2013), very close to the ideal stoichiometry of 6.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Hyder et al., 2013
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- Authors
- Hyder, F., Fulbright, R. K., Shulman, R. G., & Rothman, D. L.
- Affiliations
- Yale University (US)
- Corresponding author
- Hyder, Fahmeed
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2013-01-09
- Volume
- 33
- Issue
- 3
- Pages
- 339-347
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3587823
- OpenAlex
- W2011551406
- Cited by
- 117
- References
- 94
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 14 · 2022: 7 · 2021: 11 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 12 · 2013: 4
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-02-01)
- 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 on Aging (R01AG034953)
- National Institute of Mental Health (R01MH067528)
- National Institute of Neurological Disorders and Stroke (P30NS052519)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- glutamatergic signaling, resting-state brain activity, cerebral oxygen consumption, brain glucose metabolism, visual cortex, sleep, vegetative state, anesthesia, brain energy metabolism, consciousness
- MeSH terms
- Animals, Cognition, Electroencephalography, Energy Metabolism, Female, Glutamine, Humans, Magnetic Resonance Imaging, Male, Rodentia, Visual Cortex, Wakefulness, Positron-Emission Tomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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