Resting-state fMRI correlations: from link-wise unreliability to whole brain stability

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze both the within- and between-subject variability as well as the test-retest reliability of resting-state functional connectivity (FC) estimates in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. To this aim we adopted a statistical framework enabling us to disentangle the contribution of different sources of variability and their dependence on scan duration, and showed that the low reliability of single links can be largely improved using multiple scans per subject. Moreover, we show that practically all observed inter-region variability (at the link-level) is not significant and due to the statistical uncertainty of the estimator itself rather than to genuine variability among areas. Finally, we use the proposed statistical framework to demonstrate that, despite the poor consistency of single links, the information carried by the whole-brain spontaneous correlation structure is indeed robust, and can in fact be used as a functional fingerprint.