The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow and metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take this into account, and subsequent methods for measurement of regional glucose metabolism must be corrected accordingly in order to allow reliable quantitative comparisons of metabolite changes in activation studies. For studies of regional metabolic changes during activation quantification poses further difficulties due to limitation in resolution and partial volume effects.
In contrast to the tight coupling between regional glucose metabolism and cerebral blood flow, there is an uncoupling between flow and oxygen consumption as the latter only increases to a limited extend. The excess glucose uptake is thus not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation, and especially temporal relationships must be taken into account.
What triggers the flow increase during functional brain activation is not entirely elucidated. The demand for excess glucose uptake may be important and a possible oxygen deficit in tissue distant from the capillaries is probably of minor importance. The mechanism by which cerebral blood flow increases during activation may incorporate changes in glycolytic substrates or local changes in astrocytes or neurons that triggers the production of vasoactive substances.