UNDERSTANDING NEURODEVELOPMENT IN MACAQUES WITH DIFFERENT REARING EXPERIENCES

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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 have used a unique, naturalistic, nonhuman primate model of human childhood maltreatment to characterize the long-term impact of adverse caregiving on neurodevelopment using in vivo neuroimaging (structural MRI, diffusion tensor imaging (DTI) and MR spectroscopy). In order to understand the effects, we also studied normative brain development during the rhesus monkey infant period, and analyzed potential associations with socioemotional maturation. We scanned rhesus infants at 2 weeks, and 3, 6 and 12 months of age. Our preliminary data analysis revealed dramatic brain developmental changes during infancy (particularly striking between 2 weeks and 3 months), including increased brain volume, deepening of sulci and intense rates of myelination. We also found that at 2 weeks some brain cortical regions, such as the prefrontal cortex, were not yet myelinated. These findings underscored the high vulnerability of the brain to insults/adversity experienced at these early ages, which could result in alterations in normal brain developmental trajectories. This is, indeed, what we found in our studies: pathological brain development caused by adverse early caregiving. Our analyses revealed long-term alterations in brain white matter integrity in animals that received poor maternal care, specifically, increased fractional anisotropy (FA, a measure of microstructural rganization/integrity) in cortical regions such as frontal lobe, somatosensory, parietal and left visual cortices, during adolescence. In contrast, FA was reduced in the ventral striatum and right visual cortex. These results suggest that poor caregiving causes alterations in normal maturation of brain myelinated tracts. In the areas showing increased FA (e.g. prefrontal and parietal cortices), this was positively correlated with aggression and negatively with levels of serotonin. The increased FA could reflect increased myelination, which would increase the action potential speed of axons in the affected bundle, perhaps causing a mismatch in normal temporal encoding; and consequently altered behavior and physiology.