Amygdala lesions do not compromise the cortical network for false-belief reasoning

Abstract

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM--false-belief reasoning--suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition.

Keywords: amygdala; fMRI; false-belief; lesions; theory-of-mind.

Fig. 1.

Study design and rationale. (A) Schematic showing the design of the False-Belief Localizer task. The rows show the Story and Judgment screens for an actual trial in the False-Belief and False-Photo conditions. (B) Structural MRIs showing each patient's amygdala lesions. Displayed are 1-mm isotropic T1-weighted MRI transverse sections of the patients’ anterior medial temporal lobes. Red arrows highlight focal calcification damage in the amygdalas of patients AP and BG. (C) Evidence that the Belief > Photo contrast activates bilateral amygdala in the typically developing brain. L, left; R, right.

Fig. 2.

Whole-brain renderings of the Belief > Photo contrast in the MIT reference group (n = 462; corrected at a voxel-level familywise error of 0.05) (A), the Caltech reference group (n = 18; corrected at a cluster-level familywise error of 0.05) (B), and the amygdala-lesion patients AP (C) and BG (D) (both estimated using combined data from their two independent sessions and corrected at a cluster-level familywise error of 0.05). L, left; R, right.

Fig. 3.

Comparing global contrast typicality in the patient and Caltech reference groups (using the MIT group's unthreshholded Belief > Photo contrast map as a benchmark). The bootstrapped distribution of mean correlation in the Caltech reference group is shown in light gray, and the individual patient observations are shown in distinct colors with the patient ID indicated above the bars.