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.

Exploring the neural basis of fear produced by mental imagery: imaginal exposure in individuals fearful of spiders

“…laboratory-acquired fear), where imaginal and in vivo extinction appear to involve overlapping neural circuity [23], and partly extend such findings to naturally occurring phobic fear. Our results of increased activity in insula and cingulate cortex during phobic imagery are consistent with studies of specific phobia [18,20], scriptdriven-imagery studies of PTSD (e.g. [21]), and also neural activity observed in healthy individuals during mental imagery of emotional pictures [42].…”

“…Metaanalyses of these studies report consistent activations in fear processing areas, such as the amygdala, the insular cortex, the anterior cingulate cortex (ACC) and the anterior midcingulate cortex (MCC) [18,20]. Compared with healthy participants, phobic individuals show hyperactivation of the thalamus, cerebellum and the inferior frontal gyrus during perception of phobic stimuli [18,20]. In addition, some brain-imaging studies of PTSD have used script-driven mental imagery of trauma as symptom provocation.…”

Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies

“…Emotional responses were associated with activations of the amygdalae 50,51 , while effective emotional regulation strategies reduce amygdala reactivity 52,53 . Furthermore, anxiety disorders and mood disorders 23,[54][55][56][57][58] are characterized by amygdala hyperreactivity, normalized by effective pharmacological and psychological treatments 59,60 . Thus, our results support the role of amygdala dysfunction as a transdiagnostic mechanism, present in BPD, similarly to other disorders.…”

The case for preregistering all region of interest (ROI) analyses in neuroimaging research

“…Furthermore, theoretical grounding of the a priori ROI selection may be problematic. For instance, in a meta-analysis on specific phobias, we showed that only 19 out of 31 studies explicitly justified the choice of ROI based on previous literature (Gentili et al, 2019). Frequently, the rationale supporting ROI selection is based on vague statements or on citing previous findings without motivating how these suggest an association between a well-defined brain area and a specific mental process.…”

“…This method is ubiquitous in the fMRI literature (Poldrack, 2007). For instance, in an Activation Likelihood Meta-Analysis on specific phobia, we found that 28 out of 31 papers employed ROI approaches (Gentili, Messerotti Benvenuti, Lettieri, Costa, & Cecchetti, 2019). In principle, ROI analysis can be statistically appropriate and useful when the target brain region is defined a priori.…”