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

Abstract

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 (CMRO(2); 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 %DeltaJ(ATP) being linearly correlated with the percentage change in CMRO(2) (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 CMRO(2) (r = -0.64, P = 0.024), but positively correlated with %DeltaJ(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.

Fig. 1.

The location and magnitude of %ΔCBF and %ΔCMRO₂ in primary visual cortex during 4-, 8-, and 16-Hz visual stimulation.

Fig. 2.

Localized ¹H spectra from primary visual cortex at resting and the three visual stimulation rates (4, 8, and 16 Hz). The lactate peaks are shown at 1.33 ppm.

Fig. 3.

(A) The J_ATP at rest and the three levels of visual stimulation. The J_ATP rates at activations are independent stimulus rates. The increments at activation are small (1.4–2.0 μmol/g/min) compared with rest (11.1 μmol/g/min). (B) The aerobic and anaerobic relative contributions (as percentages) to ΔJ_ATP. The ΔJ_ATP at the three stimulation rates is predominately a result of aerobic metabolism (approximately 98%, including both neuronal and astrocytic contributions).

Fig. 4.

(A) CMRO₂–ATP coupling. Significant correlation was shown between %ΔCMRO₂ and %ΔJ_ATP at the three visual stimulation rates (r = 1.00, P < 0.001). (B) CBF–lactate coupling. Significant correlation was shown between %ΔCBF and %ΔJ_Lac at the three visual stimulation rates (r = 0.91, P < 0.001). (C) CBF–CMRO₂ coupling. Negative correlation was shown between %ΔCBF and %ΔCMRO₂ at the three visual stimulation rates (r = −0.64, P = 0.024).