Energetic cost of brain functional connectivity

Abstract

The brain's functional connectivity is complex, has high energetic cost, and requires efficient use of glucose, the brain's main energy source. It has been proposed that regions with a high degree of functional connectivity are energy efficient and can minimize consumption of glucose. However, the relationship between functional connectivity and energy consumption in the brain is poorly understood. To address this neglect, here we propose a simple model for the energy demands of brain functional connectivity, which we tested with positron emission tomography and MRI in 54 healthy volunteers at rest. Higher glucose metabolism was associated with proportionally larger MRI signal amplitudes, and a higher degree of connectivity was associated with nonlinear increases in metabolism, supporting our hypothesis for the energy efficiency of the connectivity hubs. Basal metabolism (in the absence of connectivity) accounted for 30% of brain glucose utilization, which suggests that the spontaneous brain activity accounts for 70% of the energy consumed by the brain. The energy efficiency of the connectivity hubs was higher for ventral precuneus, cerebellum, and subcortical hubs than for cortical hubs. The higher energy demands of brain communication that hinges upon higher connectivity could render brain hubs more vulnerable to deficits in energy delivery or utilization and help explain their sensitivity to neurodegenerative conditions, such as Alzheimer's disease. T he high energetic cost of human brain function, which is 10 times higher than what would be expected from its weight alone (1, 2), can only be maintained through a combination of strategies for efficient energy use (3-5). Neural communication accounts for a significant fraction of the energy consumed by the brain (6), most of which was termed "dark energy" because it reflects intrinsic activity of uncertain functional origin (7).Under normal physiological conditions, the brain derives most of its energy requirements from the metabolism of glucose and energy reserve glucose equivalents (8, 9). In vivo PET imaging studies with [ 18 F]fluorodeoxyglucose (FDG), a radiotracer used for measuring glucose metabolism, have demonstrated high baseline glucose metabolic rates in ventral posterior regions of the brain (10). The brain uses a large fraction of this energy to support synaptic transmission, which is associated with the hemodynamic responses (11,12) that are captured during stimulation studies with functional magnetic resonance imaging (fMRI) and the spontaneous oscillations captured during resting-state fMRI (R-fMRI), and also to sustain the resting potentials in neurons and glia (13,14). Thus, the high degree of connectivity of the ventral posterior regions of the brain with other brain regions (15) suggests an association between energy consumption and R-fMRI (16). However, the energy budget of the spontaneous R-fMRI signals remains largely unknown, and a better understanding of the relationship between energy consumption and functional connectivity could be v...

The Relationship between Glucose Metabolism, Resting-State fMRI BOLD Signal, and GABAA-Binding Potential: A Preliminary Study in Healthy Subjects and Those with Temporal Lobe Epilepsy

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