title: Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.
abstract: Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements.
authors.affiliation: Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University, New Haven, CT, USA Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA Department of Biomedical Engineering, Yale University, New Haven, CT, USA fahmeed.hyder@yale.edu.
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.affiliation: Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University, New Haven, CT, USA Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Herman
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bailey
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.affiliation: Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA.
authors.forename: Ronen
authors.initials: R
authors.lastname: Globinsky
authors.affiliation: Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Fulbright
authors.affiliation: Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA Quantitative Neuroscience with Magnetic Resonance (QNMR) Core Center, Yale University, New Haven, CT, USA Department of Radiology & Biomedical Imaging, Yale University, New Haven, CT, USA Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D066128:Gray Matter / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D049268:Positron-Emission Tomography
chemical_list: D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen
keywords: Default mode network; PET; energy metabolism; fMRI; glutamate; neurophysiology