Quantitative Meta-analysis Identifies Brain Regions Activated During Rectal Distension in Irritable Bowel Syndrome

Abstract

Background and Aims The responsiveness of the central nervous system (CNS) is altered in patients with irritable bowel syndrome (IBS). However, due 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 with-in 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 (thalamus, insula, anterior mid-cingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in: 1) More consistent activations in regions associated with emotional arousal [pregenual anterior cingulate cortex (pACC), amygdala]; 2) 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 CNS 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.

Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging

“…Most of the activated regions are considered to be parts of "visceral pain neuro-matrix" involved in visceral sensory processing and their activation has been consistently observed in previous visceral pain studies. 12,14,18,20,26,27,39 Among these regions, insula is the interoceptive cortex where all information about the internal state of the organism is processed. 40 It has been reported to be activated during noxious somato-sensory stimulation and suggested to play an important role in pain processing integrating visceral sensory and emotional information.…”

Symptoms and the body: Taking the inferential leap

“…Importantly, high NA appears to be a vulnerability factor for MUS when it interacts with increased self-focused attention (Gendolla et al, 2005), with previous experiences of somatic events and/or with somatic concerns (Bogaerts et al, 2014;Van den Bergh et al, 1997). As trait anxiety is associated with elevated sensitivity to threat (Hariri, 2009;Yiend, 2010) and compromised inhibitory systems for counter-regulating unpleasantness, it is likely that these mechanisms are involved in the association between high trait NA persons and MUS (Bishop, 2009;Montoya et al, 2005;Tillisch et al, 2011;Van Oudenhove and Aziz, 2013). Recently, the concept of central sensitization has been advanced to capture the idea of hyper-responsivity to various somatosensory stimuli in patients with functional somatic syndromes, characterized by elevated threat and salience detection, and a reduced capacity to down-regulate emotional responses (Bourke et al, 2015;Nijs et al, 2012 for reviews).…”

Mechanisms of Stress-induced Visceral Pain

“…[63][64][65][66] In particular, the amygdala has been found to consistently demonstrate altered activation to visceral stimulation in IBS patients. 67 The amygdala is a brain nucleus that is important for the integration of the body's neurophysiologic responses to stress, as well as modulating the perception of anxiety, which is increased in IBS. 68 The amygdala, and more specifically the central nucleus of the amygdala (CeA), is a key brain nucleus involved in the facilitation of the stress response.…”