Background The neural basis of action understanding is a hotly debated issue. The mirror neuron account holds that motor simulation in fronto-parietal circuits is critical to action understanding including speech comprehension, while others emphasize the ventral stream in the temporal lobe. Evidence from speech strongly supports the ventral stream account, but on the other hand, evidence from manual gesture comprehension (e.g., in limb apraxia) has led to contradictory findings. Aims Here we present a lesion analysis of sign language comprehension. Sign language is an excellent model for studying mirror system function in that it bridges the gap between the visual-manual system in which mirror neurons are best characterized and language systems which have represented a theoretical target of mirror neuron research. Methods & Procedures Twenty-one life long deaf signers with focal cortical lesions performed two tasks: one involving the comprehension of individual signs and the other involving comprehension of signed sentences (commands). Participants' lesions, as indicated on MRI or CT scans, were mapped onto a template brain to explore the relationship between lesion location and sign comprehension measures. Outcomes & Results Single sign comprehension was not significantly affected by left hemisphere damage. Sentence sign comprehension impairments were associated with left temporal-parietal damage. We found that damage to mirror system related regions in the left frontal lobe were not associated with deficits on either of these comprehension tasks. Conclusions We conclude that the mirror system is not critically involved in action understanding.

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