General psychopathology factor (p-factor) prediction using resting-state functional connectivity and a scanner-generalization neural network

Abstract

The general psychopathology factor (p-factor) represents shared variance across mental disorders based on psychopathologic symptoms. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to investigate functional networks (FNs) from functional magnetic resonance imaging (fMRI) associated with the psychopathology of an adolescent cohort (n > 10,000). However, the heterogeneities associated with the use of multiple sites and multiple scanners in the ABCD Study need to be overcome to improve the prediction of the p-factor using fMRI. We proposed a scanner-generalization neural network (SGNN) to predict the individual p-factor by systematically reducing the scanner effect for resting-state functional connectivity (RSFC). We included 6905 adolescents from 18 sites whose fMRI data were collected using either Siemens or GE scanners. The p-factor was estimated based on the Child Behavior Checklist (CBCL) scores available in the ABCD study using exploratory factor analysis. We evaluated the Pearson's correlation coefficients (CCs) for p-factor prediction via leave-one/two-site-out cross-validation (LOSOCV/LTSOCV) and identified important FNs from the weight features (WFs) of the SGNN. The CCs were higher for the SGNN than for alternative models when using both LOSOCV (0.1631 ± 0.0673 for the SGNN vs. 0.1497 ± 0.0710 for kernel ridge regression [KRR]; p < 0.05 from a two-tailed paired t-test) and LTSOCV (0.1469 ± 0.0381 for the SGNN vs. 0.1394 ± 0.0359 for KRR; p = 0.01). It was found that (a) the default-mode and dorsal attention FNs were important for p-factor prediction, and (b) the intra-visual FN was important for scanner generalization. We demonstrated the efficacy of our novel SGNN model for p-factor prediction while simultaneously eliminating scanner-related confounding effects for RSFC.