Finding the Imposter: Lesions Causing Capgras Syndrome Are Functionally Connected with Brain Regions Perceiving Familiarity (P4.047)

Abstract

Objective: To determine whether the abnormal belief content in Capgras delusion relates to a lesion’s functional connectivity with brain regions important for processing personal familiarity. Background: Capgras syndrome is a bizarre, fascinating disorder where a familiar person is perceived as an unfamiliar imposter. While right frontal lesions are known to impair belief monitoring and promote delusion formation, the neural mechanisms leading to the specific delusional content in Capgras syndrome remain controversial. Methods: First, we determined the neural correlates for personal familiarity by performing an ALE meta-analysis of fMRI studies in normal subjects. Next, we examined whether neuroanatomical lesions in patients with Capgras delusions (2 personal cases and 14 from the literature) were functionally connected with areas identified in our meta-analysis using a new technique called Lesion-Based Network Analysis. In this method, each individual lesion is used as a seed point to identify its functional connectivity network using a database of resting-state fMRI scans from normal subjects. Results: Our meta-analysis of 15 neuroimaging studies revealed that the left retrosplenial cortex is the region most consistently activated by personally familiar stimuli. In patients with Capgras delusion, 15/16 lesion locations (94[percnt]) were functionally anti-correlated with the left retrosplenial cortex, overlapping the area activated by personally familiar stimuli. Functional connectivity with the left retrosplenial cortex was specific to patients with Capgras syndrome compared to patients with other neurological syndromes. Conclusions: Patients with Capgras syndrome have focal lesions that are functionally connected with regions involved in personal familiarity. Our results provide a novel conceptual model to explain how one lesion causes the “two hits” that lead to a delusional disorder: a “destructive lesion” in the frontal lobe the allows for the pathological persistence of delusions and a “functional lesion” in a connected brain region that generates the delusion content.

Disclosure: Dr. Darby has nothing to disclose. Dr. Laganiere has nothing to disclose. Dr. Prasad has nothing to disclose. Dr. Fox has nothing to disclose.