Evaluating the gray and white matter energy budgets of human brain function

The insatiable appetite for energy to support human brain function is mainly supplied by glucose oxidation (CMR_glc(ox)). But how much energy is consumed for signaling and nonsignaling processes in gray/white matter is highly debated. We examined this issue by combining metabolic measurements of gray/white matter and a theoretical calculation of bottom-up energy budget using biophysical properties of neuronal/glial cells in conjunction with species-exclusive electrophysiological and morphological data. We calculated a CMR_glc(ox)-derived budget and confirmed it with experimental results measured by PET, autoradiography, ¹³C-MRS, and electrophysiology. Several conserved principles were observed regarding the energy costs for brain's signaling and nonsignaling components in both human and rat. The awake resting cortical signaling processes and mass-dependent nonsignaling processes, respectively, demand ∼70% and ∼30% of CMR_glc(ox). Inhibitory neurons and glia need 15-20% of CMR_glc(ox), with the rest demanded by excitatory neurons. Nonsignaling demands dominate in white matter, in near opposite contrast to gray matter demands. Comparison between ¹³C-MRS data and calculations suggests ∼1.2 Hz glutamatergic signaling rate in the awake human cortex, which is ∼4 times lower than signaling in the rat cortex. Top-down validated bottom-up budgets could allow computation of anatomy-based CMR_glc(ox) maps and accurate cellular level interpretation of brain metabolic imaging.