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bioRxiv · 10.1101/2025.05.21.655345

Unveiling functional-metabolic synergy in the healthy brain: multivariate integration of dynamic FDG-PET and resting-state fMRI

Tarricone, C.·Vallini, G.·Baron, G.·Silvestri, E.·Volpi, T.·Vlassenko, A. G.·Goyal, M. S.·Bertoldo, A.
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Abstract

IntroductionDespite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [18F]FDG-PET, yet much remains to be understood, particularly regarding their coupling between functional and metabolic networks. MethodsTo this end, we employed multivariate Partial Least Squares Correlation (PLSC) to investigate the functional-metabolic relationship at both nodal and network level. From dynamic [18F]FDG-PET data we estimated parameters describing glucose metabolism --delivery rate (K1), phosphorylation rate (k3), and fractional uptake (Ki)-- and generated within-individual metabolic connectivity (MC) networks. FC was derived from fMRI data filtered into two frequency bands and summarized as region-wise strength to capture nodal characteristics. ResultsOur findings revealed that glucose delivery is linked with FC strength, particularly when fMRI signal frequencies include greater hemodynamic contributions. Even stronger functional-metabolic coupling occurs at the network level in the low-frequency fMRI band, with higher MC between sensory/attention and transmodal networks supporting stronger FC within sensory/attention areas. ConclusionsBy leveraging PLSC, this work deepens our understanding of the functional-metabolic synergy in the healthy brain, providing new insights into its organization. Key PointsO_LIWe identified robust functional-metabolic synergy in the healthy brain using multivariate Partial Least Squares Correlation (PLSC), revealing strong associations between fMRI-derived functional connectivity and glucose metabolism from dynamic [{superscript 1}F]FDG-PET. C_LIO_LIAt the nodal level, glucose delivery (K1) is more strongly linked to FC strength than phosphorylation (k3) or uptake (Ki), especially in fMRI bands enriched with hemodynamic components. C_LIO_LIAt the network level, coupling between metabolic and functional connectivity is strongest in the canonical low-frequency fMRI band, suggesting that integrated metabolic support underpins large-scale functional integration across brain systems. C_LI

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Tarricone, C., Vallini, G., Baron, G., Silvestri, E., Volpi, T., Vlassenko, A. G., Goyal, M. S., Bertoldo, A.. 2025-05-27. Unveiling functional-metabolic synergy in the healthy brain: multivariate integration of dynamic FDG-PET and resting-state fMRI. https://doi.org/10.1101/2025.05.21.655345

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