Metabolic Connectivity Gradients of the Human Brain

The functional architecture of the brain is organised along continuous, macro-scale gradients. However, it is unknown if the metabolic architecture of the brain displays similar gradient characteristics. Here, we use functional positron emission tomography (fPET) with 18F-fluorodeoxyglucose (FDG) to characterise the metabolic connectivity gradients of the brain and determine how neurobiological mechanisms shape these gradients to support cognition across the adult lifespan. We identified four principal metabolic connectivity gradients, with the primary axis recapitulating the canonical unimodal-to-transmodal hierarchy from other imaging modalities. Subsequent gradients delineated specialised dimensions of metabolic organisation, including association system differentiation, hemispheric asymmetry, and sensory system segregation. These gradients were coupled to cortical thickness, baseline rates of glucose metabolism, blood flow, and gene expression related to energy metabolism, such that transmodal, control and default mode poles were more metabolically active, more interconnected, had greater cortical thickness, and were more strongly related to the expression of genes related to cellular energy production, than unimodal and sensory poles. A reduction in gradient strength at the gradient poles was associated with older age and predicted worse cognitive performance. We conclude that the metabolic organisation of the brain constitutes a genetically grounded, structurally and energetically constrained gradient hierarchy that supports cognitive function and undergoes a reorganisation in ageing.