A tale of two connectivities: intra- and inter-subject functional connectivity jointly enable better prediction of...

Naturalistic functional magnetic resonance imaging (fMRI) paradigms, such as movie viewing, are attracting increased attention, given their ability to mimic the real-world cognitive demands on attention and multimodal sensory integration. Moreover, naturalistic paradigms allow for characterizing brain network responses associated with dynamic social cognition in a model-free manner using inter-subject functional connectivity (ISFC). While intra-subject functional connectivity (FC) characterizes the individual's brain functional architecture, ISFC characterizes the neural coupling driven by time-locked extrinsic dynamic stimuli across individuals. Here, we hypothesized that ISFC and FC provide distinct and complementary information about individual differences in social cognition. To test this hypothesis, we examined a public movie-viewing fMRI dataset with 32 healthy adults and 90 typically developing children. Building three partial least squares regression (PLS) models to predict social abilities using FC and/or ISFC, we compared predictive performance to determine whether combining two connectivity measures could improve the prediction accuracy of individuals' social-cognitive abilities measured by a Theory of Mind (ToM) assessment. Our results indicated that the joint model (ISFC + FC) yielded the highest predictive accuracy and significantly predicted individuals' social cognitive abilities (rho = 0.34, p < 0.001). We also confirmed that the improved accuracy was not due to the increased feature dimensionality. In conclusion, we demonstrated that intra-/inter-subject connectivity encodes unique information about social abilities, and a joint investigation could help us gain a more complete understanding of the complex processes supporting social cognition.