Effects of phase encoding direction on test-retest reliability of human functional connectome

Abstract

The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction. However, whether and how phase encoding direction would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of phase encoding direction on global and nodal connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by phase encoding direction were consistently mapped to the cingulate cortex and temporal lobe, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Further, we demonstrated that the observed reliability differences between phase encoding directions may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could slightly, but overall have limited value to boost the ICCs. These results were largely replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that phase encoding direction has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention.