Coupling of changes in cerebral blood flow with neural activity: what must initially dip must come back up.

Activation flow coupling, increases in neuronal activity leading to changes in cerebral blood flow (CBF), is the basis of many neuroimaging methods. An early rise in deoxygenation, the "initial dip," occurs before changes in CBF and cerebral blood volume (CBV) and may provide a better spatial localizer of early neuronal activity compared with subsequent increases in CBF. Imaging modality, anesthetic, degree of oxygenation, and species can influence the magnitude of this initial dip. The observed initial dip may reflect a depletion of mitochondrial oxygen (O(2)) buffers caused by increased neuronal activity. Changes in CBF mediated by nitric oxide (NO) or other metabolites and not caused by a lack of O(2) or energy depletion most likely lead to an increased delivery of capillary O(2) in an attempt to maintain intracellular O(2) buffers.