Specificity, reliability and sensitivity of social brain responses during spontaneous mentalizing

The debilitating effects of social dysfunction in many psychiatric disorders prompt the need for systems-level biomarkers of social abilities that can be applied in clinical populations and longitudinal studies. A promising neuroimaging approach is the animated shapes paradigm based on so-called Frith-Happé animations (FHAs) which trigger spontaneous mentalizing with minimal cognitive demands. Here, we presented FHAs during functional magnetic resonance imaging to 46 subjects and examined the specificity and sensitivity of the elicited social brain responses. Test-retest reliability was additionally assessed in 28 subjects within a two-week interval. Specific responses to spontaneous mentalizing were observed in key areas of the social brain with high sensitivity and independently from the variant low-level kinematics of the FHAs. Mentalizing-specific responses were well replicable on the group level, suggesting good-to-excellent cross-sectional reliability [intraclass correlation coefficients (ICCs): 0.40-0.99; dice overlap at P uncorr <0.001: 0.26-1.0]. Longitudinal reliability on the single-subject level was more heterogeneous (ICCs of 0.40-0.79; dice overlap at P uncorr <0.001: 0.05-0.43). Posterior temporal sulcus activation was most reliable, including a robust differentiation between subjects across sessions (72% of voxels with ICC>0.40). These findings encourage the use of FHAs in neuroimaging research across developmental stages and psychiatric conditions, including the identification of biomarkers and pharmacological interventions.