Interactive effects of ageing processes and early life stress on brain structure: a neuroimaging informatics approach

Abstract

Though it is well established that ageing and early-life stress can cause changes in brain structure, there is less agreement on both region-specific changes and how interactions between ageing and early-life stress may impact on brain structure. Investigations in humans often rely on cross-sectional studies, and are confounded by a number of drawbacks and biases. These issues can be mitigated through the use of model animals, such as rhesus macaques. However, processing macaque MRI data comes with a number of issues, precluding the use of human MRI processing pipelines. Therefore, this project first involved the creation of a novel processing pipeline for macaque MRI data. The outputs of the AutoMacq pipeline had a low error-rate and high levels of reliability. As the majority of previous studies focus on brain changes in late adulthood, this project focused on the under-researched period of early to mid-adulthood. Using a longitudinal approach, significant decreases, in both cortical thickness and grey matter volume, with ageing were identified, primarily within the frontal, temporal and parietal lobes. Early weaning was utilised as a measure of early life stress. In an age- matched cross-sectional dataset, subjects weaned before 12 months showed significantly lower cortical thickness in regions of the temporal lobe, compared to those weaned after 12 months. Significant interactions between weaning and ageing were found for grey matter volume in one area of the occipital lobe, as well for cortical thickness in regions of parietal and occipital lobes. Brain areas across the whole brain appeared sensitive to ageing, whereas regions specifically involved in visual processing seemed most affected by early weaning. Overall, this project resulted in the creation of a novel macaque MRI processing pipeline, and provided new knowledge on the impacts of ageing and early-life stress on brain structure during early to mid-adulthood.