Within the brain, the regional CBF is spatially as well as temporally coupled to neuronal activity. Increased neuronal activity is accompanied by an increase in CBF, whereas during deactivation CBF is reduced. After more than a century of research, we still do not fully understand the physiological meaning of the regional CBF response to changes in cerebral activity: Vascular coupling may provide a constant glucose and oxygen supply to the activated brain tissue—on the other hand, removal of tissue metabolites as lactate may be the driving force for vasodilation. In addition, it remains unclear which signals initiate the very early blood flow response, and which factors or mechanisms mediate the sustained increase in CBF during increased neuronal activity. The CBF response to functional activation or deactivation of brain tissue induces characteristic changes in hemoglobin oxygenation, leading to microvascular hyper- or hypo-oxygenation, respectively. Stimulation-induced metabolic and vascular responses are utilized to visualize human or animal brain at work and to map brain activity. Neurometa-bolic and neurovascular coupling thus form the physiological basis for modern functional brain imaging techniques such as functional MRI, near infrared spectroscopy, and optical imaging spectroscopy. Therefore we still need to better understand the physiology of neurometabolic and neu-rovascular coupling to fully exploit the potential of modern functional brain imaging.


Capillary recruitment: Opening or closing of capillaries as a mechanism regulating microvascular blood flow according to demand.

Functional brain imaging: Investigation of stimulation-induced active brain areas by utilizing changes of metabolic or vascular parameters.

Initial dip: Early increase of the concentration of deoxyhemoglobin as evidence for early desaturation of hemoglobin and oxidative tissue metabolism at the onset of functional activation.

Neurovascular coupling: Tight temporal and spatial relationship between regional cerebral blood flow and neuronal activity.


1. Vovenko, E. (1999). Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in nor-moxia: An experimental study on rats. Pflugers Arch. 437, 617-623.

2. Villringer, A., Them, A., Lindauer, U., Einhaupl, K., and Dirnagl, U. (1994). Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study. Circ. Res. 75, 55-62.

3. Lindauer, U., Royl, G., Leithner, C., Kuhl, M., Gold, L., Gethmann, J., Kohl-Bareis, M., Villringer, A., and Dirnagl, U. (2001). No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. Neurolmage 13, 988-1001. In this publication it was shown that the method of analysis of spectroscopic data from optical imaging studies may have a considerable impact on the calculation of hemoglobin oxygenation changes under physiological as well as pathophysiological conditions.

4. Lindauer, U., Villringer, A., and Dirnagl U. (1993). Characterization of CBF response to somatosensory stimulation: Model and influence of anesthetics. Am. J. Physiol. 264, H1223-H1228.

5. Chaigneau, E., Oheim, M., Audinat, E., and Charpak, S. (2003). Two-photon imaging of capillary blood flow in olfactory bulb glomeruli. Proc. Natl. Acad. Sci. USA 100, 13081-13086.

6. Wenzel, R., Wobst, P., Heekeren, H. R., Kwong, K. K., Brandt, S. A., Kohl, M., Obrig, H., Dirnagl, U., and Villringer A. (2000). Saccadic suppression induces focal hypooxygenation in the occipital cortex. J. Cereb. Blood Flow Metab. 20, 1103-1110.

7. Buxton, R. B. (2001). The elusive initial dip. Neurolmage 13, 953-958. This article is an excellent commentary on the issue of the "initial dip," which integrates data from experimental studies with current models of the coupling of cerebral blood flow and oxygen metabolism.

8. Malonek, D., and Grinvald, A. (1996). Interactions between electrical activity and cortical microcirculation revealed by imaging spec-troscopy: Implications for functional brain mapping. Science 272, 551-554. In this publication on functional brain mapping, optical imaging spectroscopy is introduced as an experimental technique that offers high spatial, temporal, and spectral resolution. The data for the first time suggest that vascular responses within the first seconds after stimulation onset are significantly better localized than in the later phase of the vascular response.

9. Mayhew, J., Zheng, Y., Hou, Y., Vuksanovic, B., Berwick, J., Askew, S., and Coffey, P. (1999). Spectroscopic analysis of changes in remitted illumination: The response to increased neural activity in brain. Neurolmage 10, 304-326.

10. Silva, A. C., Lee, S. P., Iadecola, C., and Kim, S. G. (2000). Early temporal characteristics of cerebral blood flow and deoxyhemoglobin changes during somatosensory stimulation. J. Cereb. Blood Flow Metab. 20, 201-206.

Capsule Biography

Dr. Lindauer is heading the research group on cerebrovascular regulation within the Department of Experimental Neurology at Charité Hospital in Berlin, Germany. Her research mainly focuses on the investigation of mediators and mechanisms of neurovascular coupling as the basis for functional brain imaging.

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