The objective of this proposal is to investigate the coupling between brain activation and cerebral perfusion. The details behind this neurovascular coupling are yet unclear, but form the basis for several widely used imaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and optical imaging of intrinsic signals (OIS). To help clarify the properties of this relationship, this proposal outlines two specific goals: (l) to characterize the spatial and temporal evolution of hemoglobin oxygenation changes within and between vascular and parenchymal compartments; and (2) to determine how well these perfusion signals are coupled to underlying neuronal activity. OIS is well-suited for the proposed studies because if offers high spatial and temporal resolution, as well as the opportunity for simultaneous electrophysiological recording. A technique for extracting hemoglobin (Hb) concentration changes from the OIS images in two spatial dimensions is presented and, in combination with field potential recording, used to study spatial and temporal aspects of neurovascular coupling in rodent somatosensory cortex. The results of these experiments will influence the design and interpretation of perfusion-based brain imaging techniques, especially fMRI. Identifying aspects of the fMRI signal that more closely reflect underlying neuronal activity will improve the technique's ability to localize brain activity. This development would significantly increase its utility for pre-operative surgical planning, for example. Determining whether coupling breaks down in certain instances will also identify possible limitations to these techniques.