Region-of-interest (ROI)-based temporal mediation analysis results.

<p>We conducted a region-of-interest (ROI)-based approach to complement the results of the whole-brain temporal mediation analysis results. For a detailed description of the ROI-based temporal mediation analysis, please refer to the Materials and methods. <b>(A)</b> Based on prior literature [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref013" target="_blank">13</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref016" target="_blank">16</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref066" target="_blank">66</a>], we selected 17 a priori ROIs known for their roles in pain processing. These include areas involved in nociceptive pain processing [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref066" target="_blank">66</a>] (e.g., left and right thalamus, right second somatosensory area, and left and right dorsal-posterior insula cortex), regions associated with self-regulatory strategies in response to pain [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref016" target="_blank">16</a>] (e.g., ventromedial prefrontal cortex and nucleus accumbens), and areas linked to social information processing related to pain [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002910#pbio.3002910.ref013" target="_blank">13</a>] (e.g., pregenual anterior cingulate cortex, orbitofrontal cortex, left and right ventrolateral prefrontal cortex, left supramarginal gyrus, medial frontal gyrus, intraparietal sulcus, and right dorsolateral prefrontal cortex). <b>(B, C)</b> River plots illustrate the ROI-based temporal mediation analysis results. The results were categorized by brain mediation timing—“early” and “late.” In addition, the regions with significance in more than 2 domains were categorized as “multiple.” The plots show the temporal domains significant at a false discovery rate (FDR) <i>q</i> < 0.05, alongside adjacent time domains pruned using 2 more liberal thresholds (<i>p</i> < 0.005 and <i>p</i> < 0.01) to contextualize the results. FDR, false discovery rate; vmPFC, ventromedial prefrontal cortex; pgACC, pregenual anterior cingulate cortex; NAc, nucleus accumbens; dpINS, dorsal-posterior insular; S2, second somatosensory area; OFC, orbitofrontal cortex; vlPFC, ventrolateral prefrontal cortex; SMG, supramarginal gyrus; MFG, medial frontal gyrus; IPS, intraparietal sulcus; dlPFC, dorsolateral prefrontal cortex.</p> <p>(DOCX)</p>