Connectome-based predictive modeling of empathy in adolescents with and without the low-prosocial emotion specifier

Empathy impairments are an important part of a broader affective impairments defining the youth antisocial phenotype callous-unemotional (CU) traits and the DSM-5 low prosocial emotion (LPE) specifier. While functional connectivity underlying empathy and CU traits have been well studied, less is known about what functional connections underly differences in empathy amongst adolescents qualifying for the LPE specifier. Such information can provide mechanistic distinctions for this clinically relevant specifier. The present study uses connectome-based predictive modeling that uses whole-brain resting-state functional connectivity data to predict cognitive and affective empathy for those meeting the LPE specifier (n= 29) and those that do not (n= 57). Additionally, we tested if models of empathy generalized between groups as well as density differences for each model of empathy between groups. Results indicate the LPE group had lower cognitive and affective empathy as well as higher CU traits and conduct problems. Negative and positive models were identified for affective empathy for both groups, but only the negative model for the LPE and positive model for the normative group reliably predicted cognitive empathy. Models predicting empathy did not generalize between groups. Density differences within the default mode, salience, executive control, limbic, and cerebellar networks were found as well as between the executive control, salience, and default mode networks. And, importantly, connections between the executive control and default mode networks characterized empathy differences the LPE group such that more positive connections characterized cognitive differences and less negative connections characterized affective differences. These findings indicate neural differences in empathy for those meeting LPE criteria that may explain decrements in empathy amongst these youth. These findings support theoretical accounts of empathy decrements in the LPE clinical specifier and extend them to identify specific circuits accounting for variation in empathy impairments. The identified negative models help understand what connections inhibit empathy whereas the positive models reveal what brain patterns are being used to support empathy in those with the LPE specifier. LPE differences from the normative group and could be an appropriate biomarker for predicting CU trait severity. Replication and validation using other large datasets are important next steps.