A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments

Jordan E Theriault; Clare Shaffer; Gerald A Dienel; Christin Y Sander; Jacob M Hooker; Bradford C Dickerson; Lisa Feldman Barrett; Karen S Quigley

doi:10.1016/j.neubiorev.2023.105373

A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments

Neurosci Biobehav Rev. 2023 Oct:153:105373. doi: 10.1016/j.neubiorev.2023.105373. Epub 2023 Aug 25.

Authors

Jordan E Theriault¹, Clare Shaffer², Gerald A Dienel³, Christin Y Sander⁴, Jacob M Hooker⁴, Bradford C Dickerson⁵, Lisa Feldman Barrett⁶, Karen S Quigley⁷

Affiliations

¹ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Electronic address: [email protected].
² Northeastern University, Department of Psychology, Boston, MA, USA.
³ Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, USA.
⁴ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
⁵ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
⁶ Northeastern University, Department of Psychology, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
⁷ Northeastern University, Department of Psychology, Boston, MA, USA; VA Bedford Healthcare System, Bedford, MA, USA.

Abstract

In aerobic glycolysis, oxygen is abundant, and yet cells metabolize glucose without using it, decreasing their ATP per glucose yield by 15-fold. During task-based stimulation, aerobic glycolysis occurs in localized brain regions, presenting a puzzle: why produce ATP inefficiently when, all else being equal, evolution should favor the efficient use of metabolic resources? The answer is that all else is not equal. We propose that a tradeoff exists between efficient ATP production and the efficiency with which ATP is spent to transmit information. Aerobic glycolysis, despite yielding little ATP per glucose, may support neuronal signaling in thin (< 0.5 µm), information-efficient axons. We call this the efficiency tradeoff hypothesis. This tradeoff has potential implications for interpretations of task-related BOLD "activation" observed in fMRI. We hypothesize that BOLD "activation" may index local increases in aerobic glycolysis, which support signaling in thin axons carrying "bottom-up" information, or "prediction error"-i.e., the BIAPEM (BOLD increases approximate prediction error metabolism) hypothesis. Finally, we explore implications of our hypotheses for human brain evolution, social behavior, and mental disorders.

Keywords: Aerobic glycolysis; Autism; Axon diameter; BOLD fMRI; Brain metabolism; Depression; Gamma oscillation; Informational efficiency; Mitochondria; Norepinephrine; Prediction error; Predictive coding.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenosine Triphosphate*
Brain / diagnostic imaging
Brain / metabolism
Glucose / metabolism
Glycolysis* / physiology
Humans
Neuroimaging

Substances

Adenosine Triphosphate
Glucose

Abstract

Publication types

MeSH terms

Substances

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