Two Decades of Functional Imaging: from Nuclear Spins to Cortical Columns

Since its introduction in 1992, there has been a revolution in the ability to image brain function with functional magnetic resonance (fMRI), going from early experiments demonstrating relatively course images of activity in the visual cortex to mapping cortical columns and to “brain reading” that constructs mental experiences of an individual, all using the fact that we were endowed with a complex paramagnetic molecule sequestered in our blood vessels and that neuronal activity has spatially-specific metabolic and physiologic consequences. These two decades of fMRI is marked by incessant improvements in instrumentation, innovative developments in image acquisition and reconstruction methods, and a significant expansion in our knowledge of neurovascular coupling. Collectively, this body of work has brought us recently to the point of depicting functional activity in three dimensions, in the entire human brain with submillimeter resolution. Some aspects of these accomplishments and the rational for their pursuit is reviewed and presented together with a personal history of the development of fMRI. 121