B - 65 Adolescent Cortico-Limbic Connectivity Mediates Associations between Internalizing Symptomology and Subsequent Neurocognitive Performance

Abstract Objective During development, internalizing symptoms negatively impact broad neurocognitive functioning. Hypoconnectivity between the Cingulo-Opercular network (CON) and limbic regions has been implicated in various psychiatric disorders. Here we attempt to investigate whether CON-limbic connectivity longitudinally mediates associations between internalizing behaviors and cognitive outcomes during adolescence. Method Internalizing symptoms were measured in 2668 youth (47% female) enrolled in the Adolescent Brain Cognitive Development study using the Child Behavior Checklist. Zero-order correlations were tested between baseline (ages 9–11) internalizing symptoms (anxiety, depression, somatic complaints) and performance on NIH Toolbox® neurocognitive measures at 4-year follow-up (ages 13–15). Significantly predicted tasks were included in a structural equation model (SEM), which tested whether a latent factor representing 2-year follow-up resting-state fMRI connectivity between the CON and limbic regions (i.e., bilateral hippocampus and amygdala) mediated associations between baseline internalizing symptoms and 4-year cognitive outcomes. Results Four neurocognitive tasks (Flanker, Picture Sequence, List Sorting, Pattern Comparison) regressed significantly onto at least one internalizing symptom. An SEM which tested the mediatory effects of CON-limbic connectivity on these associations fit the data well (CFI = 0.997; SRMR = 0.007; RMSEA =0.015 [0,0.027]). Increased anxiety and somatic symptoms significantly predicted reduced CON-limbic connectivity, while depression did not. Associations between anxiety and somatic symptoms and List Sorting performance were suppressed, indicating full mediation by CON-limbic connectivity on working memory. Connectivity also partially mediated a negative association between anxiety and Flanker performance. Conclusions Our findings point to CON-limbic hypoconnectivity as a potential mechanism underlying associations between late childhood internalizing symptoms and poorer executive functioning (most notably working memory) during early adolescence.