Between- and Within-Person Heterogeneity in Adolescent Resting State Networks: Associations with Internalizing Psychopathology

项目摘要/摘要 青春期是抑郁和焦虑的关键风险期，青少年发病的精神病理学是 预示着更差的健康和生活结果。功能连接(FC)网络，反映特征 脑功能，已经成为一种有希望的生物标志物，为诊断和干预提供信息 精神变态学。然而，尽管临床组和对照组之间的FC结果存在差异，尤其是 在静息状态(RS)网络中，有最少的临床翻译。一个关键的限制是定性的 个人之间和个人内部的网络异质性威胁到在 个人层面。在人与人之间的层面上，个人之间性质上截然不同的网络限制了 群体平均网络，以有效地反映每个人。如果集团级别的网络不反映个人， 从它们得出的行为推论不适用于个人。我们的前期工作和之前的工作 精确成像研究通过证明光纤通道网络的异构性提供了这一限制的证据 在个人之间。然而，群体网络对个体的普适性还有待于实证检验。 这项建议将评估青少年RS网络从群体到个人的泛化能力，并研究 数据驱动的相似个体分组解决异质性限制的能力(目标1)。在 在个人层面上，单次扫描的FC可变性也威胁到FC网络的有效性。如果FC意味着 并且协方差在扫描过程中随时间变化(即，不是平稳的)，静态(时不变)网络将 不能有效地反映整个扫描的网络进程。本提案将对动态本位数进行评估 青少年遥感网络的平稳性，以确定静态网络的有效性(目标2)。对于这两个目标，这 该提案将使用来自青少年大脑认知发展研究的11-12岁的大样本。这个 建议书将确定数据聚合的级别(组、子组或个人)和时间精度(静态 或动态)，对于来自FC网络的个别级推断是必要的。这些发现将对最终的 使用FC网络进行临床翻译的目标，这需要个体层面的预测。然后我们将使用 准确预测青少年抑郁和焦虑结果的RS网络特征 (目标3)，建立具有更大临床翻译潜力的基础。为实现目标而制定的培训计划 拟议的项目是与相关专家团队合作开发的，该团队包括正式的 课程作业、研讨会和应用研究活动。具体地说，我将发展功能磁共振研究方面的专业知识。 和分析方法，用于子组识别的机器学习方法，以及具体的(人- 中心)完成研究方案所需的方法。培训将强调向 我的目标是成为临床神经科学领域的独立研究员，对个人进行精确的研究 神经功能与青少年精神病理学之间的联系。

PROJECT SUMMARY/ABSTRACT Adolescence is a key risk period for depression and anxiety, and adolescent-onset psychopathology is predictive of poorer health and life outcomes. Functional connectivity (FC) networks, which reflect trait-like brain functioning, have emerged as a promising biomarker to inform diagnosis and intervention of psychopathology. However, despite findings of FC differences between clinical and control groups, particularly in resting state (RS) networks, there has been minimal clinical translation. A key limitation is that qualitative network heterogeneity between- and within-individuals threatens the ability to draw inferences valid at the individual level. At the between-person level, qualitatively distinct networks across individuals limit the ability of group-averaged networks to validly reflect each individual. If group-level networks do not reflect individuals, behavioral inferences drawn from them will not apply to the individual. Our preliminary work and previous precision imaging studies provide evidence of this limitation by demonstrating FC network heterogeneity across individuals. However, the generalizability of group networks to individuals is yet to be tested empirically. This proposal will assess group-to-individual generalizability of adolescent RS networks and examine the ability of data-driven subgroups of similar individuals to address the limitation of heterogeneity (Aim 1). At the within-person level, FC variability across a single scan also threatens the validity of FC networks. If FC means and covariances vary with time across a scan (i.e., are not stationary), a static (time-invariant) network would not validly reflect network processes across the scan. This proposal will estimate dynamic FC to assess stationarity of adolescent RS networks to determine the validity of static networks (Aim 2). For both aims, this proposal will use a large 11–12-year-old sample from the Adolescent Brain Cognitive Development study. The proposal will determine the levels of data aggregation (group, subgroup, or individual) and time precision (static or dynamic) necessary for individual-level inferences from FC networks. Findings will be critical for the ultimate goal of using FC networks for clinical translation, which requires individual-level prediction. We will then use RS network features that are precise to individuals to predict depression and anxiety outcomes in adolescents (Aim 3), building a foundation with increased potential for clinical translation. The training plan to achieve the proposed project was developed in collaboration with a team of relevant experts that consists of formal coursework, workshops, and applied research activities. Specifically, I will develop expertise in fMRI research and analysis methods, machine learning approaches for subgroup identification, and idiographic (person- centered) methods necessary to complete the research proposal. Training will emphasize development toward my goal of becoming an independent investigator in clinical neuroscience who studies individually precise associations between neural functioning and adolescent psychopathology.