The story of the initial dip in fMRI.

Over the past 20 years much attention has been given to characterizing the spatial accuracy of fMRI based signals and to techniques that improve on its co-localization with neuronal activity. While the vast majority of fMRI studies have always used the conventional positive BOLD signal, alternative contrast options have demonstrated superior spatial specificity. One of these options surfaced shortly after the initial BOLD fMRI demonstrations and was motivated by optical imaging studies which revealed an early signal change that was much smaller but spatially more specific than the delayed positive response. This early signal change was attributed to oxygenation changes prior to any subsequent blood flow increases. After observation of this biphasic hemodynamic response in fMRI, because this early response resulted in a small MR signal decrease prior to the onset of the large signal increase, it became known as the "initial dip". While the initial dip in fMRI was subsequently reported by many studies, including those in humans, monkeys, and cats, there were conflicting views about the associated mechanisms and whether it could be generalized across brain regions or species, in addition to whether or not it would prove fruitful for neuroscience. These discrepancies, along with the implications that the initial dip might increase the spatial specificity of BOLD fMRI from 2 to 3mm to something more closely associated with neural activity, resulted in lot of buzz and controversy in the community for many years. In this review, the authors provide an account of the story of the initial dip in MR based functional imaging from the Minnesota perspective, where the first demonstrations, characterizations, and applications of the initial dip commenced.