Personalized Mapping of Affective Lability

项目总结 情感失调症(AL)是一种常见的精神症状，以情绪快速波动为特征。临床上 显著的AL通常开始于青春期，在精神障碍和普通人群中都存在， 也是自杀的主要危险因素。然而，AL的发育底物仍然很稀少 描述。先前的研究表明，额顶网络之间存在自上而下的调节缺陷。 (FPN)和杏仁核；FPN也被认为经历了长时间的成熟到年轻成年期。 然而，以前的努力受到与潜在生物学相关的方法学障碍的限制。 FPN的异质性。大脑皮层网络通常使用标准化的网络图谱来研究， 它假设在个体的结构和功能神经解剖学之间存在1：1的映射。然而， 最近使用精确功能定位技术的研究已经证明了可靠的个体差异 在功能地形学中，即皮层上的功能网络的空间分布。值得注意的是，FPN是 既是影响调节的关键，也是所有皮质网络中变化最大的功能拓扑。 这项提议将利用新的机器学习工具在个性化的基础上映射FPN以进行测试 最重要的假设是AL与FPN地形图的发育异常和 连通性。在目标1中，我们将继续收集30名青少年和年轻人(16-21岁)的样本。 具有情感敏感度和20个匹配的比较器，使用基于智能手机的数字表型和多 模式成像。在目标2中，我们将利用最近完成的纵向研究(n=200，10-25年 年龄，平均随访间隔=5年)，这将使我们了解如何纵向变化 与AL相关的个性化FPN拓扑和连接性。总而言之，该项目将提供 关于与AL相关的电路水平发育缺陷的有价值的新见解，并提供 在计算精神病学方面训练有素的候选人。

PROJECT SUMMARY Affective lability (AL) is a common psychiatric symptom characterized by rapid mood fluctuations. Clinically significant AL often begins in adolescence, is present in both psychiatric disorders and the general population, and is a major risk factor for suicide. However, the developmental substrates of AL remain only sparsely described. Prior studies have implicated deficits of top-down regulation between the frontoparietal network (FPN) and the amygdala; the FPN is also known to undergo protracted maturation into young adulthood. However, previous efforts have been limited by methodological obstacles related to underlying biological heterogeneity of the FPN. Cortical networks have typically been studied using standardized network atlases, which assume a 1:1 mapping between structural and functional neuroanatomy across individuals. However, recent studies using precision functional mapping techniques have demonstrated reliable individual differences in functional topography, i.e., the spatial distribution of functional networks on the cortex. Notably, the FPN is both critical for affect regulation and also has the most variable functional topography of any cortical network. This proposal will capitalize upon new machine learning tools to map the FPN on a personalized basis to test the over-arching hypothesis that AL is associated with developmental abnormalities of FPN topography and connectivity. In Aim 1, we will continue to acquire a sample of 30 adolescents and young adults (ages 16-21) with affective lability and 20 matched comparators using smartphone-based digital phenotyping and multi- modal imaging. In Aim 2, we will capitalize upon a recently-completed longitudinal study (n=200, 10-25 years old, mean follow up interval = 5 years) that will allow us to understand how longitudinal changes in personalized FPN topography and connectivity associate with AL. Taken together, this project will provide valuable new insights regarding circuit-level developmental deficits associated with AL, and provide the candidate with superb training in computational psychiatry.