Oxidative metabolism and the detection of neuronal activation via imaging

Recent years have witnessed a great growth of interest in non-invasive imaging methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), permitting identification of brain structures that mediate specific cognitive and behavioural tasks in humans. Because these techniques use physiological responses such as increased perfusion or metabolism as surrogate indicators of evoked neuronal electrical activity, understanding the role of these processes in sustaining the information processing function of neurons is vital to the proper interpretation of functional neuroimaging data. An ultimate goal of these non-invasive techniques is to approach the sensitivity and spatial resolution of earlier autoradiographic methods, which have repeatedly demonstrated exquisitely detailed delineations of neuronal response patterns using metabolic glucose uptake as a physiological tag. Although glucose is generally metabolized in conjunction with oxygen, technical challenges in imaging tissue oxygen consumption in vivo have limited the use of this complementary process in the detection of neuronal activation. In this article we review concepts linking cerebral blood flow and metabolism to neuronal activation, and compare functional imaging techniques that exploit these relationships. We also describe recently introduced MRI based methods for measurement of oxygen consumption and assess the relative contributions of different metabolic pathways during neuronal activation. Our calculations suggest that the bulk of the energy demand evoked during stimulation of neurons in visual cortex is met through oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker for increased neuronal electrical activity.