Supplementary Material for: Disrupted Prefrontal Regulation of Social Rejection in Irritable Bowel Syndrome

Introduction: Psychosocial stress plays a critical role in symptom exacerbation in irritable bowel syndrome (IBS), yet neural mechanisms linking social rejection to visceral pain remain poorly understood. This study examined the behavioral and neural responses to social rejection in patients with IBS, focusing on prefrontal regulation.
Methods: Using functional magnetic resonance imaging (fMRI) and a validated social exclusion paradigm, we compared the behavioral and neural responses of 35 patients with IBS (Rome IV criteria, without comorbid depression or anxiety disorders) and 36 matched healthy controls (HCs). Participants experienced phases of inclusion, exclusion, and re-inclusion while reporting emotional distress and abdominal pain severity.
Results: Compared to HCs, patients with IBS reported a greater increase in abdominal pain during exclusion and showed a pattern suggesting prolonged emotional distress upon re-inclusion. At the neural level, patients with IBS exhibited reduced activation in the dorsomedial prefrontal cortex (dmPFC) during exclusion and in the left inferior frontal gyrus (LIFG) during re-inclusion. Functional connectivity analyses further revealed altered interactions within prefrontal regions (LIFG-dmPFC) and between prefrontal and limbic areas (dmPFC-amygdala) in IBS. Moreover, greater dmPFC-amygdala coupling was associated with heightened emotional distress during social exclusion and was related to greater abdominal pain even at one-year follow-up.
Conclusions: These findings indicate altered engagement and coordination of prefrontal regulatory networks during social rejection in IBS, offering insights into neural mechanisms linking psychosocial stress to pain chronicity in IBS.