Mirroring fear in the absence of a functional amygdala.

F rom an evolutionary perspective, facial expressions of fear convey highly recognizable emotional signals that serve adaptive functions by promoting survival and reproductive success (1). Current theories of how the brain interprets facial expressions of fear implicate the mirror neuron network (MNN) in echoing the emotional states of others by internal simulation (2,3). Originally discovered in the ventral premotor cortex of macaque monkeys (4,5), mirror neurons are defined as being responsive to observation and execution of the same actions. Evidence that facial emotion recognition in humans is impaired by damage to MNN-associated cortical regions or the amygdala (6) has stimulated the hypothesis that the amygdala forms an integral component of an emotion MNN (7,8). An alternative view holds that the amygdala plays only a supporting role (9), for example, by directing attention to the informative eye region (10), suggesting the emotional MNN could operate independently, without a functional amygdala. To test these hypotheses directly, we studied two 38-year-old female monozygotic twins (patient 1 and patient 2) with equivalent, selective bilateral amygdala calcification damage because of congenital UrbachWiethe disease (synonyms hyalinosis cutis et mucosae or lipoid proteinosis; Online Mendelian Inheritance in Man 247100) (11–15) and 16 healthy female control subjects (mean age SD = 35.8 4.6 years). In previous experiments patient 1, but not patient 2, demonstrated preserved recognition of fearful faces and potentiated responses to them in MNN-associated regions suggesting that the MNN might functionally compensate her amygdala damage (14,15). We therefore predicted that patient 1, but not patient 2, would exhibit fear-specific supranormal MNN responses in a functional magnetic resonance imaging (fMRI) experiment (experiment 1) probing observation and imitation of