New Approaches to Functional Neuroenergetics

The coupling between brain energy metabolism andneuronal activity has fo, r more than a century ,allowedresearchers ot monotir brani funcoitn (Roy & Sher-rington, 1890; Siesjo, 1973; Sokoloff, 1981). A break-through in this effort, and one that made human studiesroutine, was the development 20 years ago of positronemission tomography, or PET (see Raichle, 1998). Incombination with experimental paradigms and modelsdeveloped in cognitive psychology, PET allowed the arsthigh-resolution metabolic maps of functionally special-ized regions of the human brain. A drawback of the PETtechnology was its reliance on cyclotron-generatedshort-lived radioisotopes. The subsequent developmentof functional magnetic resonance imaging (fMRI) madefunctional brain mapping widely available to scientists(Kwong et al., 1992; Ogawa, Menon, Kim, & Ugurbil,1992). Almost weekly, new brain imaging results arehighlighted in scientiac journals and the popular mediaas providing new insights into the biological basis ofhuman brain function and neurological and psychiatricdisorders.The application of PET and fMRI to localize cognitiveprocesses is based on the assumption that functionalneuronal activity increases when a region is involved inperforming a cognitive task (Posner & Raichle, 1994).These functional neuronal activities are involved in thecommunication of information between neurons andinclude neurotransmitter release and action potentials.The energy required for these and other brain processesis provided almost exclusively by oxidative glucose me-tabolism (Siesjo, 1978). Functional imaging measureseither glucose metabolism or neurophysiological pa-rameters coupled to glucose metabolism (Sokoloff,1981). Regions of increased functional neuroenergeticdemand are identiaed by the corresponding increase in