Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome

Abstract

Background & aims: Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences.

Methods: We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest.

Results: The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls.

Conclusions: Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

Figure 1

The graph shows rectal distension sensitivity thresholds of hyper- and normosensitive IBS patients and HCs, obtained by the ascending method of limits before the imaging experiment, sorted by sensory level. Mean values and SD are shown. Differences are calculated with a non-paired t-test.

Figure 2

a: Ratings of present intensity of gastrointestinal (GI) symptoms during the experiment. A scale ranging from 0 to 10 was used to determine (A) intensity of present GI symptoms with lowest score indicating faint intensity and highest score indicating extremely intense symptoms. Mean values and SD shown. Differences between groups are calculated with a non-paired t-test. b: Ratings of the last low and high distension of the imaging experiment. Subjects rated on a 4 point scale as no sensation (=0); some sensation (=1); urgency (=2); maximum tolerable pressure (=3). Mean and SD are shown. Differences are calculated with a non-paired t-test.

Figure 3

BOLD response (<0.01) within the ROIs in HCs (n=18), normosensitive IBS (n=18) and hypersensitive IBS (n=15) during (a) high rectal distension (45 mmHg). (b) the expectation of high rectal distension (45 mmHg) Red = increased BOLD signal, blue = decreased BOLD signal. HYP = hypersensitive IBS, NORM= normosensitive IBS, HC = HCs