Cellular and mitochondrial correlates of regional glucose metabolism in the human cortex
Regional differences in human brain glucose metabolism reflect local energy demands, but their cellular and mitochondrial determinants remain unclear. We combined [18F]FDG positron emission tomography in healthy human participants with estimates of cellular composition and mitochondrial density to unravel (sub)cellular correlates of heterogeneity in brain glucose metabolism. By correcting for RNA content and differential gene expression due to postmortem sampling, we addressed methodological shortcomings in multimodal neuroimaging integration. We introduce transcriptionally derived cytoarchitectonic maps of the human cortex that are consistent with histological findings, providing a biologically grounded framework for relating in vivo neuroimaging signals. Accordingly, mitochondrial distribution showed strong association with the intrinsic energy requirements at resting state. In contrast, relations between metabolism and neuronal composition were driven by sensory input and mitochondria-sparse thin-axon neurons, suggesting that stimulation-induced energy demand is met rather by neuronal processes that are independent of mitochondrial abundance to maintain efficient information processing.