[Prior] research raises three interesting issues, which we address briefly in this commentary. First is the organization and function of the human action understanding system and its similarity to the parietal-frontal mirror neuron system of the macaque, which appears to be involved in action understanding in monkeys. Second is the nature of the blood oxygen level dependent (BOLD) signal that is the basis of responses seen in functional magnetic resonance imaging, and how it might be altered in demyelinating disease. The third issue we address is how the brain compensates for white matter injury in action observation as gleaned from imaging studies. Finally, we will make some suggestions for future study of specialized brain mechanisms in patient samples using fMRI.