Aberrant brain structural large‐scale connectome in Crohn’s disease

Abstract

Background Disturbed brain‐gut interactions and a bidirectional relationship between inflammation and psychiatric symptoms such as anxiety and depression are being discussed in patients with inflammatory bowel diseases (IBD). Alterations of brain structure and function in IBD have been reported with heterogeneous results. Whether these changes reflect independent localized deficits or rather a systematic disruption in the anatomical organization of large‐scale brain networks remains unclear. The present study investigated the gray matter structural connectome in patients with Crohn's disease (CD). Methods Sixty participants (30 with quiescent CD and 30 matched healthy controls [HC]) underwent high‐resolution brain MRI at 3 Tesla. Well‐established graph theoretical metrics were analyzed at the global and regional network level and compared between groups. Key Results The networks in both groups followed a small‐world organization, that is, an architecture that is simultaneously highly segregated and integrated. However, transitivity, a measure of global network segregation, was significantly reduced in patients (P = 0.003). Regionally, patients showed a reduction of nodal betweenness centrality in the right insula and cuneus and the left superior frontal cortex and reduced nodal degree within the left‐hemispheric cingulate and the left lateral and right medial orbitofrontal cortex. Conclusion and Inferences These findings lend support to the hypothesis that CD is accompanied by alterations in both global network organization and regional connectivity. A deeper understanding of neural central networks in IBD may facilitate the development of complementary strategies in the treatment of “extraintestinal” comorbid conditions such as depression or anxiety.

Altered structural covariance and functional connectivity of the insula in patients with Crohn’s disease

“…Meanwhile, the PI is considered to receive emotional inputs from the thalamus, limbic, and brainstem structures, and to help with recognizing internal changes within the body (31). A reduced local connectivity in this region could be a marker of disturbed abdominal sensory perception and of altered emotional evaluation of these stimuli in CD patients (15). Therefore, the decreased GMV in the subregions of the insula might be associated with brain dysfunctions of sensory transmission and emotional processing in CD patients.…”

“…Moreover, compared to female HCs, female CD patients have been shown to have increased functional connectivity (FC) between the left anterior insula and all 4 frontoparietal network nodes, with a reciprocal FC between the right posterior parietal cortex and the left anterior insula (14). As for topology networks, CD patients showed a reduction of nodal betweenness centrality in the right insula and cuneus (15). Moreover, Rubio et al found that CD patients had significantly stronger activations in the cingulate cortex, insula, amygdala, and thalamus than did controls in the context of uncertainty concerning upcoming experimentally induced rectal discomfort (11,12).…”

Multidimensional Assessment of Interoceptive Abilities, Emotion Processing and the Role of Early Life Stress in Inflammatory Bowel Diseases

“…While the impact of the environment on the development of IBD is substantial, the role of specific factors is still poorly defined, one candidate being early life stress ( 3 – 5 ). Newer studies in IBD have suggested alterations in the brain-body communication, directly influencing the sensory and immune functions of the gastrointestinal tract ( 6 – 8 ). In line, gastrointestinal pathologies have been recently linked to altered interoceptive processes ( 9 ).…”

Exploring joint patterns of brain structure and function in inflammatory bowel diseases using multimodal data fusion

“…Patients with inflammatory bowel diseases (IBDs) like Crohn's disease (CD) and ulcerative colitis (UC) suffer from an unpredictable disease course and relapsing symptoms of intestinal inflammation such as abdominal pain and diarrhea, but also extraintestinal manifestations (EIM), fatigue, and a high prevalence of coexistent mood disorders. Changes in brain structure and function have repeatedly been described in IBD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] with heterogeneous results.…”

“…8 In terms of brain function, reduced amygdala and thalamus activity was found in UC patients in response to positive emotional visual stimuli. 4 It is noteworthy that so far, all MRI brain imaging studies examined patients with either CD [1][2][3]5,7,[10][11][12][13]15 or UC, 4,8 or a mixed IBD group, 9,14 but none have addressed putative differences between the two disorders. Both disorders share some biological features such as immune-mediated gut inflammation and partly overlapping genetic predisposition, but there are still distinct differences like predilection sites, affected layers of the intestinal wall or typical clinical symptoms.…”