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

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. •An energy-inefficient form of brain metabolism occurs after task-based stimulation.•The function of this metabolic event has remained an open neurochemical puzzle.•We hypothesize that it fuels signaling in thin, informationally-efficient axons.•BOLD increases approximate these task-elicited changes in brain metabolism.•A metabolic framework can provide a novel functional interpretation of BOLD.