ROI and phobias: The effect of ROI approach on an ALE meta-analysis of specific phobias.

About 90% of fMRI findings on specific phobias (SP) include analysis of region of interest (ROI). This approach characterized by higher sensitivity may produce inflated results, particularly when findings are aggregated in meta-analytic maps. Here, we conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on SP, testing the impact of the inclusion of ROI-based studies. ALE meta-analyses were carried out either including ROI-based results or focusing on whole-brain voxelwise studies exclusively. To assess the risk of bias in the neuroimaging field, we modified the Newcastle-Ottawa Scale (NOS) and measured the reliability of fMRI findings. Of the 31 selected investigations (564 patients and 485 controls) one-third did not motivate ROI selection: five studies did not report an explicit rationale, whereas four did not cite any specific reference in this regard. Analyses including ROI-based studies revealed differences between phobics and healthy subjects in several regions of the limbic circuit. However, when focusing on whole-brain analysis, only the anterior midcingulate cortex differentiated SP from controls. Notably, 13 studies were labeled with low risk of bias according to the adapted NOS. The inclusion of ROI-based results artificially inflates group differences in fMRI meta-analyses. Moreover, a priori, well-motivated selection of ROIs is desirable to improve quality and reproducibility in SP neuroimaging studies. Lastly, the use of modified NOS may represent a valuable way to assess and evaluate biases in fMRI studies: "low risk" of bias was reported for less than half of the included studies, indicating the need for better practices in fMRI.