This F31 application requests 3-years of funding to support my doctoral training and education in the use of multi-modal brain image processing methods to investigate stress coping-induced adaptations in prefrontal white matter connectivity. Coping with intermittent social stress is an essential aspect of living in complex social environments. Coping tends to counteract the deleterious effects of stress, and is thought to induce neuroadaptations in corticolimbic brain systems. The proposed research tests this hypothesis using an animal model of prefrontal growth and development.
Aim 1. Confirm that early postnatal stress coping-induced changes in prefrontal white matter persist into mid-life adulthood. Based on results from my preliminary analysis, I hypothesize that prefrontal white matter volumes derived from T1-weighted anatomical images and fractional anisotropy determined by diffusion tensor imaging (DTI) will be greater in animals that have previously experienced and coped with postnatal social separations compared to non-separated controls.
Aim 2. Determine whether postnatal stress coping increases prefrontal-amygdala connectivity determined by DTI. Tractography analysis of white mater tract densities as determined from DTI data will be used to test the hypothesis that prefrontal-amygdala white matter connectivity is increased in animals that have previously experienced and coped with postnatal social separations compared to non-separated controls.
Aim 3. Determine whether stress coping-induced increases in prefrontal-amygdala structural connectivity correspond with increased functional connectivity. Resting-state functional magnetic resonance imaging (fMRI) data will be used to test the hypothesis that stress coping-induced increases in prefrontal-amygdala structural connectivity determined by DTI tractography correspond with increased functional connectivity in this corticolimbic network.
According to the World Health Organization, stress will be the second leading cause of all medical disabilities by the year 2020. The potential impact of understanding the neurobiology of stress coping is therefore quite high. The research proposed in this application is designed to provide mechanistic insights for the development of diagnostic tools and therapeutics that enhance stress coping and recovery from mental illness.