Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 18; pp. 8446 - 8451
• Main Authors: Lin, Ai-Ling, Fox, Peter T, Hardies, Jean, Duong, Timothy Q, Gao, Jia-Hong
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.05.2010; National Acad Sciences
• Subjects: adenosine triphosphate; Adenosine Triphosphate - biosynthesis; Adult; Aerobiosis; Anaerobiosis; ATP; biochemical pathways; Biological Sciences; Blood; Blood flow; brain; Cerebrovascular Circulation; correlation; cortex; energy; Energy demand; Energy metabolism; Female; Humans; hyperemia; Lactates; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; metabolic diseases; Metabolism; NMR; Nonlinear Dynamics; Nuclear magnetic resonance; Oxidation-Reduction; Oxygen; Oxygen Consumption; Oxygen demand; Oxygen metabolism; Positron emission tomography; spectroscopy; Spectrum analysis; Studies; Visual cortex; Visual Cortex - blood supply; Visual Cortex - metabolism; Visual stimulation; Young Adult
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0909711107

The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production (JATP)] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO₂; i.e., index of aerobic metabolism), and lactate production (JLac; i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in JATP were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %ΔJATP being linearly correlated with the percentage change in CMRO₂ (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7-65.1%) and negatively correlated with the percentage change in CMRO₂ (r = -0.64, P = 0.024), but positively correlated with %ΔJLac (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand.