Relation-Preserving Harmonization of Functional Connectivity Representation: Ensuring Local Functional, Longitudinal, and Population-Level Consistency
摘要
Functional Connectivity Representation (FCR) free of brain parcellations, such as diffusion maps of functional connectivity, provides critical insights into brain functional organization, making it essential in neuroimaging studies. However, site-specific variability in multi-site fMRI datasets caused by scanner and imaging protocol differences introduces non-biological variability, necessitating harmonization for reproducible and generalizable cross-cohort studies. Despite existing efforts, previous methods typically overlook some critical properties during harmonization, such as local functional, longitudinal, and population-affinity relation, limiting the reliability and interpretability of downstream analyses. Therefore, we propose Relation-Preserving Functional Connectivity Representation Harmonization (RP-FCRH), a novel framework that removes site effects while preserving biologically meaningful variability in FCR. For site effect removal, RP-FCRH is built upon a Cycle-Consistent Adversarial Autoencoder (CAA), which enforces site-invariance in the latent space via a discriminator and utilizes cycle consistency to generate realistic predictions. To preserve biological variability, we introduce three relation-preserving constraints based on CAA: (1) Local Functional Stability: RP-FCRH maintains the spatial organization of local functional connectivity patterns by preserving local gradient structures, ensuring fine-grained functional relationships remain intact. (2) Longitudinal Trend Consistency: RP-FCRH preserves individual-specific developmental trajectories by minimizing deviations in longitudinal trajectories before and after harmonization. (3) Population-Level Similarity: RP-FCRH maintains similarity relationships among individuals within a cohort by constraining inter-subject distances, preventing artificial alterations in within-group characteristics. Extensive experiments on 4 fMRI datasets (1,206 scans) highlight the superiority of RP-FCRH in reducing site-specific variability while preserving critical functional connectivity relationships, demonstrating its potential in enabling more robust and generalizable cross-cohort fMRI studies.