UNDERSTANDING NEURODEVELOPMENT IN MACAQUES WITH DIFFERENT REARING EXPERIENCES

Emory University, Atlanta GA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We used a naturalistic nonhuman primate model of early life stress (ELS) consisting of poor maternal care to characterize the long-term impact on neurodevelopment using in vivo neuroimaging technology, using structural MRI, diffusion tensor imaging (DTI) and MR spectroscopy. In order to understand the effects on brain development, we had to examine normative brain development during the rhesus monkey infant period, and analyzed potential associations with socioemotional maturation. Our findings revealed dramatic brain developmental changes during infancy, particularly fast and striking between 2 weeks and 3 months, including increased brain volume, deepening of sulci and intense rates of myelination. We found that at 2 weeks some cortical regions, such as the prefrontal cortex, were not yet myelinated. These findings underscored the high vulnerability of the brain, particularly prefrontal circuits with protracted development, to stress experienced at these early ages, which could result in alterations in normal brain developmental trajectories. We demonstrated that ELS indeed affects brain development using a model of poor maternal care. For example, long-term alterations in brain myelinated tracts were detected during adolescence, particularly in prefrontal, temporal, parietal and visual cortices. We found a significant decrease in amygdala volume of animals with ELS, despite no differences in overall brain, gray or white matter volumes, or in other regions of interest (e.g. hippocampus). Interestingly, the amygdala volume negatively correlated with basal cortisol at month 1, when animals experienced the highest levels of stress as infants. Altogether, our findings suggest the ELS has long-term effects on the structure and connectivity of limbic brain regions of nonhuman primates. The reduced amygdala volume detected during the adolescent period seems related to the stress-induced elevations in cortisol early in life.