Five energy metabolism pathways show distinct regional distributions and lifespan trajectories in the human brain.

Five energy metabolic pathway maps derived from whole-brain transcriptomics show consistent spatial divergence between primarily energy-producing and anabolic pathways, particularly in unimodal sensory cortices.

• The five pathways mapped were glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and lactate metabolism.
• Curated gene sets and whole-brain transcriptomics data were used to generate the spatial maps.
• Energy-producing pathways and the anabolic PPP showed consistent divergence in their regional distributions, most notably in unimodal sensory cortices.
• The approach relied on spatially resolved transcriptomic data spanning the entire cortex.

Energy metabolic pathway maps exhibit unique relationships with the cellular and laminar organization of the cortex.

• The spatial alignment of energy pathway maps was explored against multi-scale structural and functional attributes including metabolic uptake, neurophysiological oscillations, cell type composition, laminar organization, and macro-scale connectivity.
• Results point to higher energy demands of large pyramidal cells and efferent projections.
• Both cell type composition and laminar structure were found to be relevant to the spatial patterning of energy pathways.

Primary energy-producing pathways (glycolysis, TCA cycle, OXPHOS, lactate metabolism) peak in childhood during development.

• Developmental trajectories were examined from the fetal stage to adulthood.
• The primary energy-producing pathways showed peak expression in childhood before declining toward adult levels.
• These trajectories were found to be distinct across the five metabolic pathways studied.

The anabolic pentose phosphate pathway (PPP) shows greater prenatal expression and declines throughout life.

• In contrast to the energy-producing pathways, the PPP exhibited its highest expression prenatally.
• PPP expression showed a declining trajectory from the fetal stage through adulthood.
• This trajectory was described as distinct from all other energy-producing pathways examined.

Energy metabolic pathway maps spatially align with neurophysiological oscillations and macro-scale brain connectivity.

• Spatial alignment was assessed between the five pathway maps and neurophysiological oscillations.
• Macro-scale connectivity patterns were also examined in relation to the energy pathway maps.
• These analyses were conducted alongside comparisons with metabolic uptake measures and cell type composition.