When a loved one feels unfamiliar: a case study on the neural basis of Capgras delusion.

Perception of familiar faces depends on a core system analysing visual appearance and an extended system dealing with inference of mental states and emotional responses. Damage to the core system impairs face perception as seen in prosopagnosia. In contrast, patients with Capgras delusion show intact face perception but believe that closely related persons are impostors. It has been suggested that two deficits are necessary for the delusion, an aberrant perceptual or affective experience that leads to a bizarre belief as well as an impaired ability to evaluate beliefs. Using functional magnetic resonance imaging, we compared neural activity to familiar and unfamiliar faces in a patient with Capgras delusion and an age matched control group. We provide evidence that Capgras delusion is related to dysfunctional activity in the extended face processing system. The patient, who developed the delusion for the partner after a large right prefrontal lesion sparing the ventromedial and medial orbitofrontal cortex, lacked neural activity to the partner's face in left posterior cingulate cortex and left posterior superior temporal sulcus. Further, we found impaired functional connectivity of the latter region with the left superior frontal gyrus and to a lesser extent with the right superior frontal sulcus/middle frontal gyrus. The findings of this case study suggest that the first factor in Capgras delusion may be reduced neural activity in the extended face processing system that deals with inference of mental states while the second factor may be due to a lesion in the right middle frontal gyrus.