Gastroenterology

Gastroenterology

Volume 140, Issue 1, January 2011, Pages 91-100
Gastroenterology

Clinical—Alimentary Tract
Quantitative Meta-analysis Identifies Brain Regions Activated During Rectal Distension in Irritable Bowel Syndrome

https://doi.org/10.1053/j.gastro.2010.07.053Get rights and content

Background and Aims

The responsiveness of the central nervous system is altered in patients with irritable bowel syndrome (IBS). However, because of variations in experimental paradigms, analytic techniques, and reporting practices, little consensus exists on brain responses to visceral stimulation. We aimed to identify brain regions consistently activated by supraliminal rectal stimulation in IBS patients and healthy subjects (controls) by performing a quantitative meta-analysis of published studies.

Methods

Significant foci from within-group statistical parametric maps were extracted from published neuroimaging studies that employed rectal distension. Voxel-based activation likelihood estimation was applied, pooling the results and comparing them across groups.

Results

Across studies, there was consistent activation in regions associated with visceral afferent processing (ie, thalamus, insula, anterior midcingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in that there were more consistent activations in regions associated with emotional arousal (pregenual anterior cingulate cortex, amygdala) and activation of a midbrain cluster, a region playing a role in endogenous pain modulation. Controls showed more consistent activation of the medial and lateral prefrontal cortex.

Conclusions

Patients with IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation, but similar activation of regions involved in processing of visceral afferent information. Controls have greater engagement of cognitive modulatory regions. These results support a role for central nervous system dysregulation in IBS. These findings provide specific targets for guiding development of future neuroimaging protocols to more clearly define altered brain−gut interactions in IBS.

Section snippets

Inclusionary/Exclusionary Criteria

Studies were included in the meta-analysis if the experimental design included supraliminal rectal balloon distension in male and/or female IBS subjects or controls. Supraliminal rectal distension in this setting includes both painful and nonpainful stimuli. The analysis included both functional magnetic resonance imaging and positron emission tomography studies. Foci were extracted from the results of within-group analyses. Only activated foci were considered for analysis because deactivations

Studies Meeting Inclusionary Criteria

Eighteen studies4, 7, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 yielded tabulated coordinates for 13 inflation contrasts in IBS subjects and 12 inflation contrasts for control subjects (detailed in Table 1). The ALE analysis of IBS subjects incorporated 161 foci and the control subject analysis used 147 foci.

Brain Regions Associated With Lower Gastrointestinal Stimulation in Healthy Control Subjects

The within-group analysis for control subjects is presented in Table 2 and Figure 1. Regions consistently activated in response to supraliminal lower gastrointestinal

Discussion

The current ALE meta-analysis of supraliminal rectal inflation confirms the involvement of brain regions involved in visceral sensation, emotion arousal, and attentional processes in both controls and IBS. Furthermore, the use of ALE techniques has allowed extension of these within-group analyses to an IBS vs controls comparison showing group differences, particularly that IBS patients reliably engage known emotional arousal circuitry (amygdala, pACC), but healthy control subjects did not … The

Limitations

This meta-analysis was limited by the availability of within-group activation analyses from several previously published studies of lower gastrointestinal stimulation. However, it remains the only analysis of its kind in lower gastrointestinal distension and this quantitative meta-analytic approach significantly improves on the previously published systematic reviews. The individual studies analyzed included a variety of different stimulation paradigms and protocols, so by its nature this

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    Conflicts of interest The authors disclose no conflicts.

    Funding Grant support: NIH K23 DK073451 (K.T.); NIH K08 DK 071626 (J.S.L.); NIH R24 AT 00268; NIH DK 48351, NIH P50 DK 64530 (E.A.M.).

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