fMRI: a new tool for the in vivo localization of drug actions in the brain.

Functional magnetic resonance imaging (fMRI), a still-emerging, non-invasive neuroimaging tool, has been applied to a wide range of questions in sensory, motor control, and cognitive psychology. Only more recently has it been applied to understand the sites and mechanisms of action of pharmacological agents within the human CNS. However, in so doing, a new set of problems and concerns surrounding the technique must be addressed because of the unique transduction mechanisms (both physiological and biophysical) that exist to produce the fMRI signal from the underlying neuronal activity. Experimental design and control issues become paramount in performing fMRI pharmacological protocols and in signal interpretation. With these caveats, the use of pharmacological agents with fMRI is likely to greatly increase in the near term as new questions about both brain physiology and neuropharmacological mechanisms become addressable for the first time. Examples are given using nicotine and cocaine as a prototypical agents.