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The premotor and parietal mirror neuron system (MNS) is thought to contribute to the understanding of observed actions by mapping them onto "corresponding" motor programs of the observer [1–24], but how would the MNS respond to the observation of hand actions if the observer never had hands? Would it not show changes of blood-oxygen-level dependent (BOLD) signal, because the observer lacks motor programs that can resonate [12, 25, 26], or would it show significant changes because the observer has motor programs for the foot or mouth with corresponding goals [15, 17, 19, 27, 28]? We scanned two aplasic subjects, born without arms or hands, while they watched hand actions and compared their brain activity with that of 16 control subjects. All subjects additionally executed actions with different effectors (feet, mouth, and, for controls, hands). The BOLD signal of aplasic individuals within the putative …