Functional activation studies in health and disease often depend upon perfusion related signals to localize the source of brain activity. The goal of this proposal is to investigate perfusion related signals measured using OIS, and vascular fluorescent dyes during a variety of stimulus conditions. The application of different neuroimaging techniques in both animals and humans will provide a comprehensive view of the timing, distribution and capacities of these perfusion related signals. The investigator will perform functional activation studies using OIS (multispectral and single wavelength), fMRI, fluorescent dyes and electrical measures, to determine the relationship in space and time between these perfusion dependent; and evoked potential (EP) maps. The investigator will do this in different sensory systems of rodents and humans using a variety of stimulus and behavioral paradigms. In humans, perfusion related signals obtained using optical methods intraoperatively will be compared with fMRI in the same subjects. In both species, maps obtained from each modality will be compared within and across subjects following image registration. Stimulus conditions will be varied to test the capacities and limitations of the responses. The investigator will determine the parameters that induce and overcome reduced responsiveness. He will assess the consistency and robustness of these responses by challenging them. He will perturb the physiologic state of the neuronal and vascular systems to determine specific effects on perfusion related cortical signals. Perturbations of, oxyhemoglobin concentration, vasodilation, and excitatory state of neurons will be tested. This proposal is a natural extension to the investigator's active grant where the focus was to characterize the basic temporal and spatial characteristics of optical signal responses to peripheral somesthetic stimulation. The four specific aims of this proposal are to: 1) characterize the different perfusion related signals, 2) examine the possibility of signal refractory periods, 3) challenge the responses and, 4) compare optical and fMRI time/space characteristics in humans. Since the coupling of brain function to cerebral perfusion provides the basis for a number of functional neuroimaging techniques, a precise knowledge of the specific underlying physiological mechanisms and their characteristics is essential. The experiments described here will help the investigator achieve that goal.
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