Brain metabolic-functional (de)coupling from health to glioma dysfunction.

The interplay between brain metabolism and function supports the brain's adaptive capacity in cognitively demanding processes. Prior work has linked glucose metabolism to resting-state fMRI activity, but often overlooks both hemodynamic confounders in the BOLD signal and the brain's dynamic nature. To address this, we employed a novel effective connectivity decomposition, separating symmetric partial covariance, capturing "true" statistical dependencies between regions, from antisymmetric differential covariance, reflecting directional brain flow. In 42 healthy subjects, we show that partial covariance corresponds to metabolic connectivity across regions, while node directionality relates to standardized uptake value ratio, a proxy for local glucose consumption. We subsequently tested the sensitivity of detected couplings in 43 glioma patients, identifying disruptions in both local and network-level effective-metabolic interactions that varied with tumor anatomical location. Our findings provide novel insights into the coupling between brain metabolism and functional dynamics at rest, advancing understanding of healthy and pathological brain states.