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

Abstract

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.