The quest for the best: The impact of different EPI sequences on the sensitivity of random effect fMRI group analyses

We compared the sensitivity of standard single-shot 2D echo planar imaging (EPI) to three advanced EPI sequences, i.e., 2D multi-echo EPI, 3D high resolution EPI and 3D dual-echo fast EPI in fixed effect and random effect group level fMRI analyses at 3T. The study focused on how well the variance reduction in fixed effect analyses achieved by advanced EPI sequences translates into increased sensitivity in the random effect group level analysis. The sensitivity was estimated in a functional MRI experiment of an emotional learning and a reward based learning task in a group of 24 volunteers. Each experiment was acquired with the four different sequences. The task-related response amplitude, contrast level and respective t-value were proxies for the functional sensitivity across the brain. All three advanced EPI methods increased the sensitivity in the fixed effect analyses, but standard single-shot 2D EPI provided a comparable performance in random effect group analysis when whole brain coverage and moderate resolution are required. In this experiment inter-subject variability determined the sensitivity of the random effect analysis for most brain regions, making the impact of EPI pulse sequence improvements less relevant or even negligible for random effect analyses. An exception concerns the optimization of EPI reducing susceptibility-related signal loss that translates into an enhanced sensitivity e.g. in the orbitofrontal cortex for multi-echo EPI. Thus, future optimization strategies may best aim at reducing inter-subject variability for higher sensitivity in standard fMRI group studies at moderate spatial resolution.