Longitudinal Change in Perceptual and Brain Activation Response to Visceral Stimuli in Irritable Bowel Syndrome Patients

Background & Aims: Symptom-related fears and associated hypervigilance toward visceral stimuli may play a role in central pain amplification and irritable bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to decreased salience of threat and reduction of hypervigilance. We sought to evaluate hypervigilance in IBS visceral hypersensitivity and associated brain activity. Methods: Twenty IBS patients (14 female; moderate to severe symptoms) and 14 healthy controls participated in symptom and rectal distention assessments 6 times over 12 months. In a subset of 12 IBS patients, H₂¹⁵O-positron emission tomography images were obtained during baseline, rectal distentions, and anticipation of an aversive distention during the first and last session. Statistical parametric mapping (SPM99) was used to identify areas and networks activated during each session as well as those with differential activation across the 2 sessions. Results: Perceptual ratings of the rectal inflations normalized over 12 months, whereas IBS symptom severity did not. There were no sex-related differences in these response patterns. Stable activation of the central pain matrix was observed over 12 months, and activity in limbic, paralimbic, and pontine regions decreased. During the anticipation condition, there were significant decreases in amygdala, dorsal anterior cingulate cortex, and dorsal brainstem activation at 12 months. Covariance analysis supported the hypothesis of changes in an arousal network including limbic, pontine, and cortical areas underlying the decreased perception seen over the multiple stimulations. Conclusions: In IBS patients, repeated exposure to experimental aversive visceral stimuli results in the habituation of visceral perception and central arousal, despite stable activation of networks processing visceral pain and its anticipation.

Abbreviations used in this paper:  ACC, anterior cingulate cortex , dACC, dorsal anterior cingulate cortex , dmPFC, dorsomedial prefrontal cortex , EMS, emotional motor system , iACC, infragenual portion of anterior cingulate cortex , LCC, locus coeruleus complex , MCC, midcingulate cortex , PAG, periaqueductal gray , PET, positron emission tomography , rCBF, regional cerebral blood flow , ROI, region-of-interest , sACC, supragenual portion of anterior cingulate cortex , SSR, stress symptom rating , SVC, small volume correction , vmPFC, ventromedial prefrontal cortex