Orygen, Parkville, Australia; Centre for Youth mental Health, The University of Melbourne, Australia.
Donders Institute, Radboud University, Nijmegen, the Netherlands; Radboud University Medical Centre, Nijmegen, the Netherlands.
Neuroimage. 2022 Dec 1;264:119699. doi: 10.1016/j.neuroimage.2022.119699. Epub 2022 Oct 20.
The potential of normative modeling to make individualized predictions from neuroimaging data has enabled inferences that go beyond the case-control approach. However, site effects are often confounded with variables of interest in a complex manner and can bias estimates of normative models, which has impeded the application of normative models to large multi-site neuroimaging data sets. In this study, we suggest accommodating for these site effects by including them as random effects in a hierarchical Bayesian model. We compared the performance of a linear and a non-linear hierarchical Bayesian model in modeling the effect of age on cortical thickness. We used data of 570 healthy individuals from the ABIDE (autism brain imaging data exchange) data set in our experiments. In addition, we used data from individuals with autism to test whether our models are able to retain clinically useful information while removing site effects. We compared the proposed single stage hierarchical Bayesian method to several harmonization techniques commonly used to deal with additive and multiplicative site effects using a two stage regression, including regressing out site and harmonizing for site with ComBat, both with and without explicitly preserving variance caused by age and sex as biological variation of interest, and with a non-linear version of ComBat. In addition, we made predictions from raw data, in which site has not been accommodated for. The proposed hierarchical Bayesian method showed the best predictive performance according to multiple metrics. Beyond that, the resulting z-scores showed little to no residual site effects, yet still retained clinically useful information. In contrast, performance was particularly poor for the regression model and the ComBat model in which age and sex were not explicitly modeled. In all two stage harmonization models, predictions were poorly scaled, suffering from a loss of more than 90% of the original variance. Our results show the value of hierarchical Bayesian regression methods for accommodating site variation in neuroimaging data, which provides an alternative to harmonization techniques. While the approach we propose may have broad utility, our approach is particularly well suited to normative modeling where the primary interest is in accurate modeling of inter-subject variation and statistical quantification of deviations from a reference model.
规范建模从神经影像学数据中进行个体化预测的潜力使得能够进行超越病例对照方法的推断。然而,站点效应通常以复杂的方式与感兴趣的变量混淆,并可能偏差规范模型的估计,这阻碍了规范模型在大型多站点神经影像学数据集上的应用。在这项研究中,我们建议通过将其包含在层次贝叶斯模型中作为随机效应来适应这些站点效应。我们比较了线性和非线性层次贝叶斯模型在建模年龄对皮质厚度的影响方面的性能。我们在实验中使用了 ABIDE(自闭症脑成像数据交换)数据集的 570 名健康个体的数据。此外,我们还使用了自闭症患者的数据来测试我们的模型是否能够在去除站点效应的同时保留临床有用的信息。我们将提出的单阶段层次贝叶斯方法与几种常用的处理加性和乘性站点效应的调和技术进行了比较,这些技术包括使用两阶段回归回归出站点效应和调和站点效应,包括使用 ComBat 进行调和,其中包括明确保留年龄和性别引起的方差作为感兴趣的生物变异,以及使用 ComBat 的非线性版本。此外,我们还从尚未适应站点的原始数据中进行了预测。根据多种指标,提出的层次贝叶斯方法显示出最佳的预测性能。除此之外,所得的 z 分数显示出几乎没有残留的站点效应,但仍保留了临床有用的信息。相比之下,回归模型和 ComBat 模型的性能特别差,其中没有明确建模年龄和性别。在所有两阶段调和模型中,预测结果都很差,原始方差损失超过 90%。我们的结果表明,层次贝叶斯回归方法在适应神经影像学数据中的站点变化方面具有价值,这为调和技术提供了替代方法。虽然我们提出的方法可能具有广泛的适用性,但我们的方法特别适合规范建模,主要关注准确建模受试者间的变化和对参考模型的偏差的统计量化。