Data-analytical stability in second-level fMRI inference

We investigate the impact of decisions in the second-level (i.e. over subjects) inferential process in functional Magnetic Resonance Imaging (fMRI) on 1) the balance between false positives and false negatives and on 2) the data-analytical stability (Qiu et al., 2006; Roels et al., 2015), both proxies for the reproducibility of results. Second-level analysis based on a mass univariate approach typically consists of 3 phases. First, one proceeds via a general linear model for a test image that consists of pooled information from different subjects (Beckmann et al., 2003). We evaluate models that take into account first-level (within-subjects) variability and models that do not take into account this variability. Second, one proceeds via permutation-based inference or via inference based on parametrical assumptions (Holmes et al., 1996). Third, we evaluate 3 commonly used procedures to address the multiple testing problem: family-wise error rate correction, false discovery rate correction and a two-step procedure with minimal cluster size (Lieberman and Cunningham, 2009; Bennett et al., 2009). Based on a simulation study and on real data we find that the two-step procedure with minimal cluster-size results in most stable results, followed by the family- wise error rate correction. The false discovery rate results in most variable results, both for permutation-based inference and parametrical inference. Modeling the subject-specific variability yields a better balance between false positives and false negatives when using parametric inference.

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