Interactive effects of affective experiences and ageing processes on brain networks over the life course: a neuroimaging informatics approach

背景：压力经历被认为是大多数非传染性疾病的主要风险因素，并被怀疑会加速衰老。然而，不同的情感体验如何影响大脑，这些影响如何在一生中积累，以及它们如何与衰老过程相互作用，在很大程度上是未知的。这个博士研究生的目标是回答这些问题。人类研究受到自我报告、对过去经历的回顾性评估以及进行随机纵向研究的困难的限制，这些研究确定了大脑特征是暴露于压力的原因还是结果。非人类灵长类动物在大脑连接，社会行为和下丘脑-垂体-肾上腺（HPA）轴发育方面与人类的相似性使它们成为克服人类研究局限性的首选模型，并回答有关压力体验的基本问题。 目标和实验方法：这个学生将利用我们正在进行的纵向数据库在世界上独一无二，结合健康猕猴大脑的半年结构（T1，T2和DTI）和功能（静息状态）MRI扫描，家庭笼行为，血液和毛发样本的视频记录，以及健康和暴露于科学和饲养程序的详细记录。学生将首先沿着两个正交的维度，唤醒和效价（积极与消极），猕猴的情感体验随机分配给动物的程序诱导，使用基于血液和MRI生物标志物，行为和皮质醇水平的互补方法。然后，博士生将评估衰老和不同的情感体验如何随着时间的推移改变大脑网络的结构和功能，以及情感体验是否会加速或减缓衰老效应。这将使用受试者内纵向方法，通过将尖端的统计和计算方法应用于我们的MRI数据集，结合分形几何，拓扑，图论和预测建模的方法来完成。最后，这些结果还将与从大型公开数据库中识别的患有情感障碍的人类患者的大脑网络进行比较。 影响：该项目将识别由情感体验改变的大脑网络，并将测试体验可以加速或减缓大脑衰老的假设。然后，这些知识可以用于评估新的干预措施在情感障碍中使这些网络正常化的效率，其中这些网络是异常的。

Background: Stressful experiences are considered the main risk factor for most non-communicable diseases and are suspected to accelerate ageing. However, how different affective experiences affect the brain, how these effects accumulate over lifetime and how they interact with ageing processes is largely unknown. The goal of this PhD studentship is to answer these questions. Human studies are limited by self-report, retrospective assessment of past experiences, and the difficulty of running randomised longitudinal studies determining whether brain characteristics identified are the cause or the consequence of the exposure to stress. The similarity of non-human primates to humans in terms of brain connectivity, social behaviour, and hypothalamic-pituitary-adrenal (HPA) axis development make them the model of choice to overcome the limitations of human studies, and answer the fundamental questions about stressful experiences. Objectives and Experimental Approach: This studentship will take advantage of our on-going longitudinal database unique in the world that combines biannual structural (T1, T2 and DTI) and functional (resting-state) MRI scans of healthy macaque brains, video recordings of home-cage behaviour, blood and hair samples and detailed records of health and exposures to scientific and husbandry procedures. The student will first characterise along two orthogonal dimensions, arousal and valence (positive versus negative), the affective experiences of macaques induced by procedures randomly assigned to animals, using complementary approaches based on blood and MRI biomarkers, behaviour, and cortisol levels. The PhD student will then assess how both ageing and different affective experiences modify structural and functional brain networks over time, and whether affective experiences accelerate or decelerate ageing effects. This will be done using a within-subject longitudinal approach, by applying cutting-edge statistical and computational methods to our MRI datasets, combining approached from fractal geometry, topology, graph theory, and predictive modelling. Finally, these results will also be compared to brain networks of human patients suffering from affective disorders, identified from large publicly available databases. Impact: This project will identify brain networks modified by affective experiences and will test the hypothesis that experiences can accelerate or decelerate brain ageing. This knowledge can then be used to assess the efficiency of new interventions at normalizing these networks in affective disorders where these networks are abnormal.