Within- and between-subject reproducibility and variability in multi-modal, longitudinal brain networks

Abstract

Network analysis provides new and important insights into the function of complex systems such as the brain by examining structural and functional networks constructed from diffusion Magnetic Resonance Imaging (dMRI), functional MRI (fMRI) and Electro/Magnetoencephalography (E/MEG) data. Although network models can shed light on cognition and pathology, questions remain regarding the importance of these findings, due in part to the reproducibility of the core measurements and subsequent modeling strategies. In order to ensure that results are reproducible, we need a better understanding of within- and between-subject variability over long periods of time. Here, we analyze a longitudinal, 8 session, multi-modal (dMRI, and simultaneous EEG-fMRI), and multiple task imaging data set. We first investigate the reproducibility of individual brain connections and network measures and find that across all modalities, within-subject reproducibility is higher than between-subject reproducibility, reaffirming the ability to detect individual differences in network structure in both structural and functional human brain networks. We see high variability in the reproducibility of pairwise connections between brain regions, but observe that in EEG-derived networks, during both rest and task, alpha-band connectivity is consistently more reproducible than networks derived from other frequency bands. Further, reproducible connections correspond to strong connections. Structural networks show a higher reliability in network statistics than functional networks, and certain measures such as synchronizability and eigenvector centrality are consistently less reliable than other network measures across all modalities. Finally, we find that structural dMRI networks outperform functional networks in their ability to identify individuals using a fingerprinting analysis. Our results highlight that functional networks likely reflect state-dependent variability not present in structural networks, and that the analysis of either structural or functional networks to study individual differences should depend on whether or not one wants to take into account state dependencies of the observed networks.