Enhanced interhemispheric functional connectivity in patients with functional anorectal pain

Functional anorectal pain (FAP) is a chronic condition with unclear pathophysiological mechanisms that is often linked to psychological distress. This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated aberrant interhemispheric connections in 30 FAP patients versus 21 matched healthy controls (HC) via seed-based functional connectivity (FC) and voxel-mirrored homotopic connectivity (VMHC). Compared with HC, FAP patients presented enhanced FC between the left middle frontal gyrus (MFG.L) and regions such as the right MFG (MFG.R) and left superior temporal gyrus (STG.L). VMHC analysis revealed increased patterns in the MFG.L and left superior medial frontal gyrus (SFGmed.L) in FAP patients. Moreover, the strength of FC between the MFG.L and MFG.R was negatively correlated with age, indicating that this heightened connection may diminish with age. These findings indicate that FAP involves aberrant interhemispheric hyperconnectivity, which may play crucial roles in pain perception and emotional processing. The age-dependent decline in FC highlights the eroding of neuroplasticity in aging patients. These neural alterations could serve as diagnostic biomarkers and provide targets for therapeutic interventions. Our work positions FAP within a brain-gut axis dysregulation framework and suggests circuit-specific therapeutics to restore neural homeostasis.