Prefrontal Executive Control Rescues Risk for Anxiety Associated with High Threat and Low Reward Brain Function

Compared with neural biomarkers of risk for mental illness, little is known about biomarkers of resilience. We explore if greater executive control-related prefrontal activity may function as a resilience biomarker by "rescuing" risk associated with higher threat-related amygdala and lower reward-related ventral striatum activity. Functional MRI was used to assay baseline threat-related amygdala, reward-related ventral striatum, and executive control-related prefrontal activity in 120 young adult volunteers. Participants provided self-reported mood and anxiety ratings at baseline and follow-up. A moderation model revealed a significant three-way interaction wherein higher amygdala and lower ventral striatum activity predicted increases in anxiety in those with average or low but not high prefrontal activity. This effect was specific to anxiety, with the neural biomarkers explaining ~10% of the variance in change over time, above and beyond baseline symptoms, sex, age, IQ, presence or absence of DMS-IV diagnosis, and both early and recent stress. Our findings are consistent with the importance of top-down executive control in adaptive regulation of negative emotions, and highlight a unique combination of neural biomarkers that may identify at-risk individuals for whom the adoption of strategies to improve executive control of negative emotions may prove particularly beneficial.