Pooling FMRI data: meta-analysis, mega-analysis and multi-center studies

Abstract

The quantitative analysis of pooled data from related functional magnetic resonance imaging (fMRI) experiments has the potential to significantly accelerate progress in brain mapping. Such data-pooling can be achieved through meta-analysis (the pooled analysis of published results), mega-analysis (the pooled analysis of raw data) or multi-site studies, which can be seen as designed mega-analyses. Current limitations in function-location brain mapping and how data-pooling can be used to remediate them are reviewed, with particular attention to power aggregation and mitigation of false positive results. Some recently developed analysis tools for meta- and mega-analysis are also presented, and recommendations for the conduct of valid fMRI data pooling are formulated.

Keywords: fMRI; false positive results; mega-analysis; meta-analysis; multi-center studies; power; random effects analysis; study design.

Figure 1

Parametric Voxel-based Meta-analysis. Step 1: the coordinates for each study are plotted in standard space brain (MNI). Step 2: After smoothing with a uniform kernel of size r, each study map is transformed into an indicator map, where voxels with 1 values (red) indicate the presence of at least one activation within distance r. Step 3: all study-level indicator maps are summed and then divided by the number of studies n, to obtain a summary map reflecting the proportion of studies reporting an activation within distance r of each voxel. Step 4: the p value of the observed proportion is computed, under the null hypothesis that the activations are generated at random spatial locations. The final thresholded map reflects the areas where the proportion of studies reporting activation is too high to have been generated by such null random process alone. In this example of a meta-analysis of language production in healthy subjects, Broca's area and anterior cingulate are revealed as areas of significant activation (Costafreda et al., 2009a).

Figure 2

Bootstrap 95% confidence intervals for the mean locations of peak activations in a meta-analysis of phonological and semantic verbal fluency activations in the left inferior frontal gyrus. Updated version of the analysis in Costafreda et al. (2006): the systematic literature search has been updated to September 2008 with a total of 25 studies included, and the bootstrap method has been modified to take into account the clustered nature (activations within studies) of the data. The conclusions are the same as the ones in the published paper. Left lateral view of a rendered image of the brain (MNI template). The confidence intervals (CI) for the mean location of peak BOLD responses associated with semantic verbal fluency (red) were significantly more ventral (z-axis) than for those for phonological verbal fluency (blue) at α = 0.05. Areas of intersections of the CI (phonological semantic) are shown in mauve.