Comprehensive evaluation of pipelines for classification of psychiatric disorders using multi-site resting-state fMRI datasets

Objective classification biomarkers that are developed using resting-state functional magnetic resonance imaging (rs-fMRI) data are expected to contribute to more effective treatment for psychiatric disorders. Unfortunately, no widely accepted biomarkers are available at present, partially because of the large variety of analysis pipelines for their development. In this study, we comprehensively evaluated analysis pipelines using a large-scale, multi-site fMRI dataset for major depressive disorder (MDD). We explored combinations of options in four sub-processes of the analysis pipelines: six types of brain parcellation, four types of functional connectivity (FC) estimations, three types of site-difference harmonization, and five types of machine-learning methods. A total of 360 different MDD classification biomarkers were constructed using the SRPBS dataset acquired with unified protocols (713 participants from four sites) as the discovery dataset, and datasets from other projects acquired with heterogeneous protocols (449 participants from four sites) were used for independent validation. We repeated the procedure after swapping the roles of the two datasets to identify superior pipelines, regardless of the discovery dataset. The classification results of the top 10 biomarkers showed high similarity, and weight similarity was observed between eight of the biomarkers, except for two that used both data-driven parcellation and FC computation. We applied the top 10 pipelines to the datasets of other psychiatric disorders (autism spectrum disorder and schizophrenia), and eight of the biomarkers exhibited sufficient classification performance for both disorders. Our results will be useful for establishing a standardized pipeline for classification biomarkers.