Hippocampal-Prefrontal Connectivity Prior to the COVID-19 Pandemic Predicts Stress Reactivity

BACKGROUND: By adolescence, foundational cognitive and affective neurobehavioral processes specialize based on environmental demands, such as stress, to determine the basis of adult trajectories. The ongoing COVID-19 pandemic has increased stress for everyone, particularly adolescents who face unique stressors such as restrictions in socialization and education. However, variability in brain processes supporting stress reactivity is not well understood. Here, we leverage pre-pandemic brain development studies to identify how maturity of prefrontal connectivity with the amygdala and hippocampus (HPC) is associated with response to COVID-19. We hypothesized that age-related changes in connectivity of affective and cognitive brain systems may underlie the emotional response of adolescents during the pandemic. METHODS: In this study, 10- to 31-year-old participants (n = 111) completed resting-state functional magnetic resonance imaging scans prior to the pandemic and then completed a questionnaire 9 months into the pandemic measuring worry, COVID-related stress, sadness, perceived stress, and positive affect. Associations between pairwise functional connectivity of HPC/amygdala subregions with prefrontal cortex subdivisions and affective reactivity during the pandemic were examined. RESULTS: Regression analyses indicated that both worry and COVID-19–related stress increased with age (false discovery rate–corrected p < .05). Furthermore, greater connectivity between the anterior ventromedial prefrontal cortex and posterior HPC was associated with greater worry and COVID-19–related stress (p < .05 corrected), which was primarily driven by individuals younger than 18 years. CONCLUSIONS: Taken together, our results indicate that increases in stress reactivity to the COVID-19 pandemic across the transition to adulthood are driven by maturation of posterior HPC–ventromedial prefrontal cortex coupling, which integrates stress response and emotional memory processing.