Appraising the brain's energy budget.

Abstract

In the average adult human, the brain represents about 2% of the body weight. Remarkably, despite its relatively small size, the brain accounts for about 20% of the oxygen and, hence, calories consumed by the body (1). This high rate of metabolism is remarkably constant despite widely varying mental and motoric activity (2). Despite these well-known facts about the brain’s large energy budget, a clear understanding of how it is apportioned among the many ongoing functional processes in neurons and glial cells has not been clearly spelled out. Understanding these relationships has assumed new importance because of the rapidly increasing use of modern imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to study the functions of the living human brain in both health and disease. Both of these techniques and their derivatives [e.g., single photon emission tomography (SPECT) and various optical imaging techniques] use measurements related to the brain’s metabolism and circulation to draw inferences about brain function in terms of its cellular activity (for review, see ref. 3). In this issue of PNAS, two papers from investigators at Yale University (4, 5) provide important new information on the relationship between brain energy metabolism and cellular activity. This information, when understood in the context of other extant information, allows new insights into the manner in which we employ both neuroimaging and neurophysiological techniques to probe the functions of the human brain. Together with other work, it also lends considerable support to conceptualization of the instantiation of functional processes themselves. The two reported studies in this issue of PNAS (4, 5) combined magnetic resonance spectroscopy (MRS) techniques with the extracellular recording of neuronal activity in the cerebral cortex of the anesthetized rat. With MRS, the investigators were able to assess changes in brain oxygen consumption as well as changes in the flux of the excitatory amino acid glutamate, the brain’s primary excitatory transmitter during somatosensory stimulation. These MRS measurements were complemented by measurements of the change in neuronal activity (i.e., spike frequency, or cell firing rate in this instance) during somatic sensory stimulation. The experimental strategy used two levels of anesthesia (i.e., deep and shallow) designed to achieve two different levels of baseline activity to which stimulus-induced changes could be related. Two observations emerge from this work. First, the change in oxygen consumption produced by stimulation was proportional to the change in excitatory or glutamatergic neurotransmitter f lux, which, in turn, was proportional to the change in spike frequency. Establishing these relationships was important to the second phase of this work showing that the maximum values of oxygen consumption and spike frequency achieved during stimulation were approximately the same from both baselines (i.e., both levels of anesthesia). The authors assert that an overall level of ongoing activity must be achieved for a particular function to occur. Thus, if the baseline level of activity of the brain is artificially suppressed, as it was in this case by anesthesia, it must be ‘‘restored’’ to the level found in the awake state as a necessary component of the functionally related activity. To put this second point into proper perspective, it is important to establish some possible ground rules about what is meant by the term ‘‘baseline’’ or ongoing activity; what this might reflect in terms of brain function; and how this baseline activity relates to transient changes in activity that have been generally termed ‘‘activations.’’ The Cost of Ongoing or Baseline Activity