Characterising structural brain development trajectories between childhood and adulthood and their relationship with mental health outcomes

确定儿童和成年之间的大脑发育轨迹是神经科学的核心任务。尽管最近的证据提供了在群体水平上大脑发育轨迹的见解，但青少年时期大脑结构变化的个体间差异仍然知之甚少(1)。两个主要因素阻碍了这一研究领域的进展：1)缺乏高分辨率的颞叶神经成像数据，阻碍了我们描述长期个体大脑结构变化的能力；2)使用线性建模技术来捕捉已知的非线性大脑结构变化，如皮质厚度（1-3）。为了解决这些限制，最近的研究已经开始使用新的建模技术来描述个体水平上的大脑成熟（2,3）。Fuhrmann等人（2022）证明，青春期皮质厚度的变化可以通过将非线性混合模型拟合到12波神经成像数据集来精确量化个体和大脑区域。这种方法允许提取大脑结构发育的一个新参数，即皮层变薄的中点（MCT），指的是青春期皮层变薄最快的时间点。MCT在个体之间显示出数年的差异。这就提出了一个问题，即不同的环境因素是否会影响大脑成熟的速度，以及大脑成熟的速度如何与未来的心理健康结果相关（1,4）。目前的博士项目旨在解决这一文献空白，使用非线性建模方法和新兴的纵向数据集（即HUBU， N = 90(5)，青少年大脑和认知发展研究/ABCD， N ~ 11,000）(6)来表征大脑结构发展的个体轨迹（即皮质厚度，白质发育）。这个博士项目将确定重要的环境预测因素和个体间皮质变薄速度变化的心理健康结果。这将促进该领域目前的方法方法，为理论发展提供信息，并最终指导未来的预防工作。该博士项目旨在1)描述从童年到成年的大脑结构发育的个体间差异，2)确定大脑结构发育轨迹的重要预测因素和结果。将开展四个项目，探讨以下四个研究问题：1)个体和白质束的发育轨迹是否存在差异？皮质厚度和白质髓鞘形成的发育轨迹在个体和大脑区域之间是否存在差异？3)社会经济剥夺如何与发展后期的心理健康结果相关？4)是否存在一个发展级联，即环境压力源预测大脑发育速度的个体间差异，而大脑发育速度的个体间差异反过来又预测心理健康结果？

Identifying brain development trajectories between childhood and adulthood is a core task in neuroscience. Although recent evidence has provided insight into trajectories of brain development at the group-level, inter-individual differences in structural brain changes during adolescence remain poorly understood (1). Two main factors have impeded progress in this research area: 1) a paucity of high-resolution temporal neuroimaging data, precluding our ability to characterise protracted individual changes in brain structure over time, and 2) the use of linear modelling techniques to capture structural brain changes that are known to be non-linear, such as cortical thickness (1-3). To address these limitations, recent studies have begun to use novel modelling techniques to delineate brain maturation at the individual level (2, 3). Fuhrmann et al. (2022) demonstrate that changes in cortical thickness during adolescence can be quantified with precision across individuals and brain regions by fitting a non-linear mixed model to a 12-wave neuroimaging dataset. This approach allowed for the extraction of a novel parameter of structural brain development, the midpoint of cortical thinning (MCT), referring to the time-point in adolescence where cortical thinning is most rapid. The MCT showed differences of several years between individuals. This raises the question of whether different environmental factors influence the pace of brain maturation, as well as how the pace of brain maturation relates to future mental health outcomes (1, 4). The current PhD project aims to address this gap in the literature, using non-linear modelling approaches and emerging longitudinal datasets (i.e., HUBU, N = 90 (5), Adolescent Brain and Cognitive Development Study/ABCD, N ~ 11,000)(6) to characterise individual trajectories of structural brain development (i.e., cortical thickness, white matter development). This PhD project will identify important environmental predictors and mental health outcomes of inter-individual variability in the pace of cortical thinning. This will advance current methodological approaches in the field, inform theory development, and, ultimately, guide future prevention work.This PhD project aims to 1) characterise inter-individual variability in structural brain development from childhood to adulthood, and 2) identify important predictors and outcomes of structural brain development trajectories. Four projects will be conducted, examining the following four research questions: 1) Do developmental trajectories of white matter integrity differ between individuals and white matter tracts? 2) Do developmental trajectories of cortical thickness and white matter myelination differ between individuals and brain regions? 3) How does socio-economic deprivation relate to mental health outcomes later in development?4) Is there a developmental cascade where environmental stressors predict inter-individual variability in the pace of brain development, which, in turn, predict mental health outcomes?