PT  - JOURNAL ARTICLE
AU  - Richard B. Buxton
TI  - The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow
AID  - 10.1101/833855
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 833855
4099  - http://biorxiv.org/content/early/2020/03/04/833855.short
4100  - http://biorxiv.org/content/early/2020/03/04/833855.full
AB  - Several current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain and decreases when oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O2/CO2 ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not due to feedback from a hypothetical O2 sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O2 and CO2 transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.