Introduction

An understanding of the physical and physiological origins of functional magnetic resonance imaging (fMRI) is critical for the effective design and analysis of experiments. The origins of fMRI, like those of MRI itself, rest on the twin foundations of nuclear magnetic resonance and image formation. But, for images to provide information about function, there must be a physiological marker of neuronal activity that is measurable by MRI. Such a marker was identified in 1990 with the discovery that the signal intensity of some forms of MR images was decreased in the presence of paramagnetic deoxygenated blood. This phenomenon, now known as blood-oxygenation-level-dependent (BOLD) contrast, forms the basis for nearly all fMRI studies.

In this chapter, we will first discuss how the MRI signal is generated, using a combination of strong static magnetic fields and brief electromagnetic pulses, followed by how that signal is modulated across space, using magnetic field gradients. Then, we will consider how neuronal activity evokes local metabolic demands that in turn alter the amount of deoxygenated hemoglobin present in nearby blood vessels. We will integrate the physics and physiology by describing the changes in BOLD contrast measurable on T₂*-weighted MR images and the pulse sequences used to collect those images.

Following the introduction of these core concepts, we will turn to a set of key topics that guide much current research into fMRI methodology. In many ways, the idea of fMRI as a single technique is misleading: there are almost as many approaches to the collection of fMRI data as there are researchers in the field. And, as improvements are made in scanner hardware, pulse sequences, and experimental design, even the most central concepts may change. We therefore highlight selected advances, both well-established and speculative, that promise to allow new research questions to be addressed by fMRI.