Although PFC is typically thought to exert top-down control over subcortical structures, our analyses revealed that this was not the case for individuals with higher polygenic externalizing scores. Bilateral amygdala was found to influence left IFG in high polygenic scorers, whereas the opposite direction of influence was observed for low scorers. This connectivity pattern with PFC is in contrast to what has been observed in healthy individuals. For example, Etkin et al. (2006) examined interregional connectivity during an emotional conflict task in a sample of healthy subjects and found a significant inverse relationship between activity in rostral cingulate and right amygdala when emotional conflict resolution demand was high. This finding suggests that rostral cingulate may help regulate emotional reactivity in part by decreasing engagement of the amygdala in response to emotional distractors in healthy individuals. Our findings suggest that this pattern may be reversed in individuals with higher polygenic associations with externalizing disorders, such that amygdala has greater influence on prefrontal cognitive control structures, at least during resting state.
