# Bridging glucose metabolism and intrinsic functional organization of the human cortex

**Authors:** Bin Wan, Valentin Riedl, Gabriel Castrillon, Matthias Kirschner, Sofie L. Valk

PMC · DOI: 10.1038/s42003-026-09693-w · Communications Biology · 2026-02-10

## TL;DR

This study shows how the brain's functional organization is linked to its energy use, with strong connections playing a key role in metabolic efficiency.

## Contribution

The study reveals a novel link between macroscale functional brain organization and regional glucose metabolism.

## Key findings

- Strong functional connections are more closely associated with regional energy expenditure than weaker ones.
- Functional gradients explain a large proportion of variability in cortical glucose metabolism.
- Brain organization is more effective than random configurations in explaining energy expenditure patterns.

## Abstract

The human brain requires a continuous supply of energy to function effectively. Here, we investigated how the low-dimensional organization of intrinsic functional connectivity patterns based on resting-state functional magnetic resonance imaging relates to brain energy expenditure measured by fluorodeoxyglucose positron emission tomography. By incrementally adding more dimensions of brain organization (via functional gradients), we show that increasing amounts of variance in the map of brain energy expenditure are accounted for. Dimensions of brain organization that explained much of the variance in intrinsic brain function also accounted for a substantial share of regional variance in energy expenditure maps. This relationship was especially pronounced for maps based on the strongest connections, suggesting that weaker connections may contribute less to explaining regional energy variance. Notably, our topological model was more effective than random brain organization configurations, suggesting that brain organization may be specifically associated with energy optimization. Our results demonstrate how the spatial organization of functional connections is systematically linked to optimized energy expenditure in the human brain, providing new insights into the metabolic basis of brain function.

Using simultaneous FDG-PET and resting-state fMRI combined with diffusion-map functional gradients, Wan et al. demonstrate that the low-dimensional spatial organization of intrinsic functional connectivity explains a large proportion of regional variability in cortical glucose metabolism. Together, these findings suggest that brain energy expenditure is tightly constrained by macroscale functional topology, with the strongest functional connections playing a dominant role in metabolic optimization and hemispheric energy organization.

## Linked entities

- **Chemicals:** fluorodeoxyglucose (PubChem CID 53716604)

## Full-text entities

- **Chemicals:** fluorodeoxyglucose (MESH:D019788), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12992575/full.md

## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12992575/full.md

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Source: https://tomesphere.com/paper/PMC12992575