Directed information flow across the metabolic network of the human brain

Abstract Brain function is organized in distributed circuits in which regional engagement unfolds over time, reflecting coordinated and temporally ordered patterns of neural computation and information flow. Neural activity also depends on a reliable and scalable supply of glucose. Yet, the temporal order and direction of metabolic signaling in brain circuits remain unknown. Here, we combine functional Positron Emission Tomography (fPET) with [18F]-flurodeoxyglucose and Granger causality analysis to characterize directed metabolic connectivity in cognitive control, memory, and affective regulatory circuits in 86 healthy adults. We observed widespread directed metabolic influences within the circuits, with the strength of connections a significant predictor of cognition and affect. The behavioral value of the connections was also governed by the efficiency with which baseline glucose metabolism was converted into adaptive functional connections. We conclude that the brain is organized into metabolic circuits that coordinate temporally ordered connectivity to support information transfer. Directed connections vary in their efficiency of glucose use and functional benefit, suggesting that metabolic signaling does not follow a simple “more is better” rule but reflects context-dependent optimization across cognitive systems.