1. ¹Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA
2. ²National Institute of Child Health and Human Development, Bethesda, Maryland, USA

Correspondence: Dr B Stefanovic, Cerebral Microcirculation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room B1D109, Bethesda, MD 20892-1065, USA. E-mail: stefanovicb@ninds.nih.gov

Received 5 October 2007; Revised 26 October 2007; Accepted 30 October 2007; Published online 5 December 2007.

Abstract

The spatiotemporal evolution of cerebral microcirculatory adjustments to functional brain stimulation is the fundamental determinant of the functional specificity of hemodynamically weighted neuroimaging signals. Very little data, however, exist on the functional reactivity of capillaries, the vessels most proximal to the activated neuronal population. Here, we used two-photon laser scanning microscopy, in combination with intracranial electrophysiology and intravital video microscopy, to explore the changes in cortical hemodynamics, at the level of individual capillaries, in response to steady-state forepaw stimulation in an anesthetized rodent model. Overall, the microcirculatory response to functional stimulation was characterized by a pronounced decrease in vascular transit times (20% 8% ), a dilatation of the capillary bed (10.9% 1.2% ), and significant increases in red blood cell speed (33.0% 7.7% ) and flux (19.5% 6.2% ). Capillaries dilated more than the medium-caliber vessels, indicating a decreased heterogeneity in vessel volumes and increased blood flow-carrying capacity during neuronal activation relative to baseline. Capillary dilatation accounted for an estimated 18% of the total change in the focal cerebral blood volume. In support of a capacity for focal redistribution of microvascular flow and volume, significant, though less frequent, local stimulation-induced decreases in capillary volume and erythrocyte speed and flux also occurred. The present findings provide further evidence of a strong functional reactivity of cerebral capillaries and underscore the importance of changes in the capillary geometry in the hemodynamic response to neuronal activation.