Points of contact between neuronal physiology and fMRI

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DESCRIPTION (provided by applicant): Despite the fact that functional magnetic resonance imaging (fMRI) studies have become ubiquitous and are of ever increasing importance for clinical and basic neurosciences, the fundamental relationships between blood oxygenation level dependent (BOLD) and electrophysiological responses regarding spatial extent and amplitude are not well understood. Numerous BOLD studies at a coarse scale (several millimeter to centimeter) indicated a fair correlation between the foci of hemodynamic activity and the spatial localization of brain functions known from traditional single unit and lesion studies. However, the BOLD signal is not a direct measure of neuronal activity per se. Rather, it is a complex convolution of changes in cerebral metabolic rate of oxygen (CMR02), cerebral blood flow (CBF) and cerebral blood volume (CBV) following focal neuronal activity. Therefore, a direct and linear correlation between the amplitude of the observable BOLD signals and the underlying neural activity at the neurophysiologically important, sub-millimeter scale can therefore not be assumed a priori. In the present study, we suggest to address these questions in a direct manner. First, we propose to perform single/multi unit recording and BOLD fMRI from the same sites of the cat primary visual cortex using a novel "Cartesian grid" technique recently developed in our laboratory. Second, we will elucidate the contribution of spiking and subthreshold cortical activity in the observed BOLD contrast by carefully mapping the extraclassical versus classical receptive field boundaries. Third, neuroactive compounds that are known to influence the balance between excitatory and inhibitory cortical activity will be infused focally during functional MRI scans. In particular, the effect of GABA and bicuculline (CABALA antagonist) on the amplitude, time course, and spatial extend of BOLD signals will be tested. In summary, we believe that our project will provide pivotal insights into the fundamental points of contact between the observable, and ubiquitous BOLD contrast and its underlying neurophysiological origin.