Hippocampal - prefrontal connectivity prior to COVID-19 pandemic predicts stress reactivity

Perica, Maria I.; Ravindranath, Orma Calabro Finnegan J.; Foran, William Luna Beatriz

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, but 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 (AMY) and hippocampus (HPC) is associated with response to COVID-19. We hypothesized that age-related change in connectivity of affective and cognitive brain systems may underlie the emotional response of adolescents during the pandemic. Methods 111 10-31 year olds completed resting state fMRI scans prior to the pandemic and then completed a questionnaire nine months into the pandemic measuring worry, COVID-related stress, sadness, perceived stress, and positive affect. Associations between pairwise functional connectivity of HPC/AMY subregions with prefrontal cortex (PFC) subdivisions and affective reactivity during the pandemic were examined. Results Regression analyses indicated that both worry and COVID-related stress increased with age (p < 0.05 FDR corrected). Furthermore, greater connectivity between anterior ventromedial PFC (vmPFC) and posterior HPC (pHPC) was associated with greater worry and COVID-related stress (p < 0.05 FDR corrected), which was primarily driven by individuals under 18. Conclusion 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 pHPC-vmPFC coupling, which integrates stress response and emotional memory processing.