Stability and similarity of the pediatric connectome as developmental outcomes

Abstract

Patterns of functional connectivity are unique at the individual level, enabling test-retest matching algorithms to identify a subject from among a group using only their functional connectome. Recent findings show that accuracies of these algorithms in children increase with age. Relatedly, the persistence of functional connectivity (FC) patterns across tasks and rest also increases with age. This study investigated the hypothesis that within-subject stability and between-subject similarity of the whole-brain pediatric connectome are developmentally relevant outcomes. Using data from 210 help-seeking children and adolescents, ages 6-21 years (Healthy Brain Network Biobank), we computed whole-brain FC matrices for each participant during two different movies (MovieDM and MovieTP) and two runs of task-free rest (all from a single scan session) and fed these matrices to a test-retest matching algorithm. We replicated the finding that matching accuracies for children and youth (ages 6-21 years) are low (18-44%), and that cross-state and cross-movie accuracies were the lowest. Results also showed that parcellation resolution and the number of volumes used in each matrix affect fingerprinting accuracies. Next, we calculated three measures of whole-connectome stability for each subject: cross-rest (Rest1-Rest2), crossstate (MovieDM-Rest1), and cross-movie (MovieDM-MovieTP), and three measures of within-state between-subject connectome similarity for Rest1, MovieDM, and MovieTP. We show that stability and similarity were correlated, but that these measures were not related to age. A principal component analysis of these measures yielded two components that we used to test for brain-behavior correlations with IQ, general psychopathology, and social skills measures (n=119). The first component was significantly correlated with the social skills measure (r=-0.26, p=0.005). Post hoc correlations showed that the social skills measure correlated with both cross-rest stability (r=-0.29, p=0.001) and with connectome similarity during MovieDM (r=-0.28, p=0.002). These findings suggest that the stability and similarity of the whole-brain connectome relate to overall brain development, and in particular, to those regions that support social skills. We infer that the development of the functional connectome simultaneously achieves patterns of FC that are distinct at the individual subject level, that are shared across individuals, and that are persistent across states and across runs--features which presumably combine to optimize neural processing during development. Future longitudinal work could reveal the developmental trajectories of stability and similarity of the connectome. Highlights- Identification algorithms yielded low accuracies in this developmental sample. - Individual differences in FC were not as persistent across states or movies. - Connectome within-subject stability and between-subject similarity were interrelated. - Stability during rest and similarity during a movie correlate with social skills scores.