During the past two decades, blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has become the scientific technique of choice for investigating human brain function in the field of cognitive neuroscience. It exploits the local alterations in blood flow produced by changes in neural activity, termed neurovascular coupling. However, BOLD fMRI does not measure neural activity directly and hence a fundamental problem exists: how to interpret BOLD signal changes and make inferences about the neural activity that generates them. This is far from straightforward because the mechanisms linking events that produce neural changes to BOLD signaling are highly complex. For example, increased BOLD activity in a vast range of tasks and experimental conditions is interpreted as indicating areas of increased neural activity. However, many neural circuits in the brain are inhibitory and little is known about what corresponding fMRI signals are generated. Would an inhibitory neural signal be expected to generated negative BOLD for example? Consequently, multi-modal experiments that directly compare different indicators of hemodynamic activity and electrophysiological measures of neural signals are necessary if BOLD contrast is to be correctly interpreted.
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