? ? In the past few years we investigated the neuroenergetic and neurochemical basis of blood-oxygenation level dependent (BOLD) functional MRI (fMRI) signal at 7T in rat brain. A major achievement in this research endeavor is that we can now obtain high-resolution maps of energy metabolism (CMRO2) from calibrated fMRI an approach that has been validated by independent 13C MRS measurements of """"""""C glutamate turnover. We have found that the fMRI signal-changes (DS/S) in the cortex are linked with alterations in energy metabolism (DCMR02/CMR02) of glutamatergic synapses and the release of glutamate from presynaptic neurons. These results relate DS/S to excitatory neurotransmission and energy metabolism of glutamatergic neurons. Although recent fMRI research efforts have shown qualitative agreement between electrical activity and the fMRI signal, in terms of spatial location and relative changes, the fundamental difference between the origins of electrophysiological and fMRI signals has to be overcome in order for BOLD to become an accurate neuroimaging tool. This research proposal is intended to bridge the gap between electrophysiological and fMRI data of the rat brain. We will investigate whether localized functional activation of cerebral cortex uses total or incremental neuronal activity to process sensory inputs. We will explore if the localized neuronal activation is regionally in accord with the neurovascular response. We will then try to examine if there is a quantitative relationship between the rates of neuronal firing and energy metabolism. Our final objective will be to determine if the dynamic neuronal response can be modeled from dynamic fMRI measurements. The main consequence of this proposal is to relate DS/S to activity of a neuronal population, and therefore, create the link between neuronal activity and fMRI (RFA-NS-02-009).
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