Regional aerobic glycolysis in the human brain

Abstract

Aerobic glycolysis is defined as glucose utilization in excess of that used for oxidative phosphorylation despite sufficient oxygen to completely metabolize glucose to carbon dioxide and water. Aerobic glycolysis is present in the normal human brain at rest and increases locally during increased neuronal activity; yet its many biological functions have received scant attention because of a prevailing energy-centric focus on the role of glucose as substrate for oxidative phosphorylation. As an initial step in redressing this neglect, we measured the regional distribution of aerobic glycolysis with positron emission tomography in 33 neurologically normal young adults at rest. We show that the distribution of aerobic glycolysis in the brain is differentially present in previously well-described functional areas. In particular, aerobic glycolysis is significantly elevated in medial and lateral parietal and prefrontal cortices. In contrast, the cerebellum and medial temporal lobes have levels of aerobic glycolysis significantly below the brain mean. The levels of aerobic glycolysis are not strictly related to the levels of brain energy metabolism. For example, sensory cortices exhibit high metabolic rates for glucose and oxygen consumption but low rates of aerobic glycolysis. These striking regional variations in aerobic glycolysis in the normal human brain provide an opportunity to explore how brain systems differentially use the diverse cell biology of glucose in support of their functional specializations in health and disease.

Fig. 1.

Distribution of aerobic glycolysis in resting human brain using GI (n = 33, groupwise t test, |Z|>4.4, P < 0.0001, cluster > 99, corrected for multiple comparisons). Specifically, regions with significantly high glycolysis include bilateral prefrontal cortex, bilateral lateral parietal lobe, posterior cingulate/precuneus, gyrus rectus, bilateral lateral temporal gyrus, and bilateral caudate nuclei. In contrast, cerebellum and bilateral inferior temporal gyrus have significantly low levels of aerobic glycolysis.

Fig. 2.

Results of conjunction analysis between resting aerobic glycolysis using the GI and BOLD correlation maps of the default and cognitive control systems. (A) Regions with elevated aerobic glycolysis (n = 33, groupwise t test, Z > 4.4, P < 0.0001, cluster > 99, corrected for multiple comparisons). (B) Default system as delineated by BOLD correlation mapping (n = 20, groupwise t test, Z > 3.0, P < 0.01, cluster > 17, corrected for multiple comparisons). (C) Cognitive control system defined as in B. (D) Intersection of voxels showing significantly elevated GI and membership in either the default or cognitive control systems.