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Mirroring Fear in the Absence of a Functional Amygdala

Published:December 14, 2012DOI:https://doi.org/10.1016/j.biopsych.2012.10.029
      From an evolutionary perspective, facial expressions of fear convey highly recognizable emotional signals that serve adaptive functions by promoting survival and reproductive success (
      • Darwin C.
      The Expression of the Emotions in Man and Animals.
      ). 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 (
      • Bastiaansen J.A.
      • Thioux M.
      • Keysers C.
      Evidence for mirror systems in emotions.
      ,
      • Keysers C.
      • Gazzola V.
      Expanding the mirror: vicarious activity for actions, emotions, and sensations.
      ). Originally discovered in the ventral premotor cortex of macaque monkeys (
      • di Pellegrino G.
      • Fadiga L.
      • Fogassi L.
      • Gallese V.
      • Rizzolatti G.
      Understanding motor events: a neurophysiological study.
      ,
      • Gallese V.
      • Fadiga L.
      • Fogassi L.
      • Rizolatti G.
      Action recognition in the premotor cortex.
      ), 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 (
      • Adolphs R.
      • Damasio H.
      • Tranel D.
      • Cooper G.
      • Damasio A.
      A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping.
      ) has stimulated the hypothesis that the amygdala forms an integral component of an emotion MNN (
      • Carr L.
      • Iacoboni M.
      • Dubeau M.
      • Mazziotta J.
      • Lenzi G.
      Neural mechanisms of empathy in humans: a relay from neural systems for imitation to limbic areas.
      ,
      • Keysers C.
      • Gazzola V.
      Towards a unifying neural theory of social cognition.
      ). An alternative view holds that the amygdala plays only a supporting role (
      • van der Gaag C.
      • Minderaa R.
      • Keysers C.
      Facial expressions: what the mirror neuron system can and cannot tell us.
      ), for example, by directing attention to the informative eye region (
      • Adolphs R.
      • Gosselin F.
      • Buchanan T.W.
      • Tranel D.
      • Schyns P.
      • Damasio A.R.
      A mechanism for impaired fear recognition after amygdala damage.
      ), 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 Urbach-Wiethe disease (synonyms hyalinosis cutis et mucosae or lipoid proteinosis; Online Mendelian Inheritance in Man 247100) (
      • Strange B.
      • Hurlemann R.
      • Dolan R.
      An emotion-induced retrograde amnesia in humans is amygdala- and β-adrenergic-dependent.
      ,
      • Hurlemann R.
      • Patin A.
      • Onur O.
      • Cohen M.
      • Baumgartner T.
      • Metzler S.
      • et al.
      Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans.
      ,
      • Hurlemann R.
      • Wagner M.
      • Hawellek B.
      • Reich H.
      • Pieperhoff P.
      • Amunts K.
      • et al.
      Amygdala control of emotion-induced forgetting and remembering: evidence from Urbach-Wiethe disease.
      ,
      • Becker B.
      • Mihov Y.
      • Scheele D.
      • Kendrick K.M.
      • Feinstein J.
      • Matusch A.
      • Aydin M.
      • et al.
      Fear processing and social networking in the absence of a functional amygdala.
      ,
      • Scheele D.
      • Mihov Y.
      • Kendrick K.M.
      • Feinstein J.S.
      • Reich H.
      • Maier W.
      • Hurlemann R.
      Amygdala lesion profoundly alters altruistic punishment.
      ) 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 (
      • Becker B.
      • Mihov Y.
      • Scheele D.
      • Kendrick K.M.
      • Feinstein J.
      • Matusch A.
      • Aydin M.
      • et al.
      Fear processing and social networking in the absence of a functional amygdala.
      ,
      • Scheele D.
      • Mihov Y.
      • Kendrick K.M.
      • Feinstein J.S.
      • Reich H.
      • Maier W.
      • Hurlemann R.
      Amygdala lesion profoundly alters altruistic punishment.
      ). 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 dynamic face expressions and hand movements. Furthermore, we expected that if the amygdala forms an essential component of an emotional MNN, then patient 2 would exhibit impaired imitation of fearful faces (experiment 2). Both experiments were approved by the Institutional Review Board of the Medical Faculty of the University of Bonn, and all participants provided written informed consent.
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