近日，美国范德比尔特大学Simon Vandekar等研究人员合作发现，研究设计特征增加大脑广泛关联研究的可复制性。2024年11月27日，《自然》杂志在线发表了这项成果。

通过对来自Lifespan Brain Chart Consortium的63项纵向和横向MRI研究（共77695个扫描）的分析和荟萃分析，研究人员展示了优化研究设计对增加标准化效应量，和可复制性在全脑范围关联研究（BWAS）中的重要性。

关于大脑体积与年龄关联的荟萃分析表明，具有较大协变量变异性和纵向研究的BWAS报告了较大的标准化效应量。通过分析来自英国生物库和阿尔茨海默病神经影像学计划的年龄效应，研究人员显示通过采样方案修改研究设计，可以提高标准化效应量和可复制性。

为了确保结果的广泛适用性，研究人员进一步评估了纵向采样方案在青少年大脑与认知发展数据集中对认知、精神病理学和人口学关联的影响。

研究人员证明，常用的纵向模型假设被试之间和被试内的变化相等，反而可能降低标准化效应量和可复制性。明确建模被试之间和被试内的效应可以避免它们的混淆，并使得每个效应量的标准化效应量得到优化。

总的来说，这些结果为改善BWAS可复制性的研究设计提供了指导。

据介绍，BWAS是发现大脑与行为之间关联的基础工具。近期的几项研究表明，为了确保BWAS的良好可复制性，需要成千上万的研究参与者。

附：英文原文

Title: Study design features increase replicability in brain-wide association studies

Author: Kang, Kaidi, Seidlitz, Jakob, Bethlehem, Richard A. I., Xiong, Jiangmei, Jones, Megan T., Mehta, Kahini, Keller, Arielle S., Tao, Ran, Randolph, Anita, Larsen, Bart, Tervo-Clemmens, Brenden, Feczko, Eric, Dominguez, Oscar Miranda, Nelson, Steven M., Schildcrout, Jonathan, Fair, Damien A., Satterthwaite, Theodore D., Alexander-Bloch, Aaron, Vandekar, Simon

Issue&Volume: 2024-11-27

Abstract: Brain-wide association studies (BWAS) are a fundamental tool in discovering brain–behaviour associations1,2. Several recent studies have shown that thousands of study participants are required for good replicability of BWAS1,2,3. Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium4 (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized effect sizes and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger variability of the covariate and longitudinal studies have larger reported standardized effect size. Analysing age effects on global and regional brain measures from the UK Biobank and the Alzheimer’s Disease Neuroimaging Initiative, we showed that modifying study design through sampling schemes improves standardized effect sizes and replicability. To ensure that our results are generalizable, we further evaluated the longitudinal sampling schemes on cognitive, psychopathology and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset. We demonstrated that commonly used longitudinal models, which assume equal between-subject and within-subject changes can, counterintuitively, reduce standardized effect sizes and replicability. Explicitly modelling the between-subject and within-subject effects avoids conflating them and enables optimizing the standardized effect sizes for each separately. Together, these results provide guidance for study designs that improve the replicability of BWAS.

DOI: 10.1038/s41586-024-08260-9

Source: https://www.nature.com/articles/s41586-024-08260-9