DESCRIPTION (provided by applicant): Common non-invasive methods for studying the human brain function, such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), are based on imaging some of the consequences of neuronal activity (i.e., increased blood flow to active areas of the brain) rather than reflecting this activity directly. However, the relationship between neuronal activity and blood flow - neurovascular coupling - is not well understood. The assumption that this relationship is linear and similar across subjects, brain areas, and experimental conditions may not always be valid, especially when individuals of varying age and cardiopulmonary fitness levels are compared. One significant limitation of most studies testing the linearity assumption is that only the hemodynamic signal is manipulated and measured, without an independent measure of neuronal activity. In this proposal we intend to use a novel approach to the investigation of neurovascular coupling, based on recording non-invasive optical brain imaging data in young adults, and in older adults selected for being high or low in cardiopulmonary fitness. Optical methods provide simultaneously recorded but independent measures of hemodynamic (near-infra-red spectroscopy, or NIRS) and neuronal (the event-related optical signal, or EROS) activity. Event-related brain potentials (ERPs) and the BOLD fMRI response will also be recorded in the same subjects and conditions to provide an external validation to this approach. Our specific goals are to determine whether and under which conditions the overall relationship between neuronal and hemodynamic signals is linear; what are the parameters of this function, and whether they vary with age, fitness, area of the brain, and sensory, motor and cognitive load. This approach is intended to provide an empirical, systematic, and parametric methodology for describing the neurovascular coupling in different brain regions and subject populations. We believe that this approach will provide data that will help explicate the relationship between neuronal and vascular events and provide a bridge between neuronal and hemodynamic imaging methods.