Impairment of social cognition in multiple sclerosis: Amygdala atrophy is the main predictor

Background: Patients with multiple sclerosis (MS) frequently reveal social behavior disturbance. Nevertheless, little is known regarding the impact of MS on social cognition, particularly theory of mind (ToM), and its neural basis. Objectives: To explore how ToM is affected in MS and its neural correlates. Methods: Enrolled 60 consecutive MS patients and 60 healthy controls (HC) matched on age, sex, and education. Participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain magnetic resonance imaging (MRI). Using Freesurfer software, cortical and subcortical gray matter (GM) volumes were calculated. Results: MS patients performed worse on Eyes Test (58.7%13.8% vs 81.9%+/- 10.4%, p<0.001) and Videos Test (75.3%+/- 9.3% vs 88.1%+/- 7.1%, p<0.001). Eyes Test performance in MS was positively correlated with the volume of subcortical structures (amygdala, putamen) and cortical regions (entorhinal cortex, fusiform gyrus, superior temporal gyrus, superior parietal gyrus, supramarginal gyrus, medial orbitofrontal cortex, anterior and posterior cingulate gyrus). In regression analysis, amygdala volume was the single predictor of performance (R-2 change=0.064, p=0.031), and a mediation analysis indicated that it contributes for the differences observed between MS and HC. Conclusion: Patients with MS have impairment on social cognition. Amygdala atrophy was the main predictor probably due to its central position within the social brain network.