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

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 (J_ATP)] 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 (J_Lac; i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in J_ATP were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %ΔJ_ATP being linearly correlated with the percentage change in CMRO₂ (r = 1.00, P < 0.001). In contrast, taskinduced 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 %ΔJ_Lac (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.