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      Role of brain imaging in disorders of brain–gut interaction: a Rome Working Team Report

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          Abstract

          Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain–gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.

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          Most cited references126

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          Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.

          During rest, multiple cortical brain regions are functionally linked forming resting-state networks. This high level of functional connectivity within resting-state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting-state functional magnetic resonance imaging time-series with diffusion tensor imaging scans. Nine consistently found functionally linked resting-state networks were retrieved from the resting-state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting-state networks. Our results show that well-known anatomical white matter tracts interconnect at least eight of the nine commonly found resting-state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal-frontal networks. Our results suggest that the functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.
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            Brain-gut microbiome interactions and functional bowel disorders.

            Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              The subjective experience of pain: where expectations become reality.

              Our subjective sensory experiences are thought to be heavily shaped by interactions between expectations and incoming sensory information. However, the neural mechanisms supporting these interactions remain poorly understood. By using combined psychophysical and functional MRI techniques, brain activation related to the intensity of expected pain and experienced pain was characterized. As the magnitude of expected pain increased, activation increased in the thalamus, insula, prefrontal cortex, anterior cingulate cortex (ACC) and other brain regions. Pain-intensity-related brain activation was identified in a widely distributed set of brain regions but overlapped partially with expectation-related activation in regions, including the anterior insula and ACC. When expected pain was manipulated, expectations of decreased pain powerfully reduced both the subjective experience of pain and activation of pain-related brain regions, such as the primary somatosensory cortex, insular cortex, and ACC. These results confirm that a mental representation of an impending sensory event can significantly shape neural processes that underlie the formulation of the actual sensory experience and provide insight as to how positive expectations diminish the severity of chronic disease states.

                Author and article information

                Journal
                2985108R
                3923
                Gut
                Gut
                Gut
                0017-5749
                1468-3288
                14 August 2019
                07 June 2019
                September 2019
                04 February 2020
                : 68
                : 9
                : 1701-1715
                Affiliations
                [1 ]G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicine at UCLA Los Angeles, California, USA
                [2 ]Neurogastroenterology Group, Queen Mary University of London, London, UK
                [3 ]Departments of Anaesthetics and Clinical Neurology, Pembroke College, Oxford, UK
                [4 ]Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg, Duisburg, Germany
                [5 ]Division of Biomedical Sciences, McGill University, Canada
                [6 ]Translational Research in Gastrointestinal Disorders, KU Leuven Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium
                [7 ]Center for Pain and the Brain, Boston Children’s, Massachusetts General and McLean Hospitals, Harvard Medical School Boston, Massachusetts, USA
                Author notes

                Contributors: EAM: study design, writing of Individual sections and overall manuscript generation.JL: neuroimaging analysis. QA: planning of study; critical review of manuscript. IT: neurobiology of treatment effects. LK: sex differences. SE: Gaps in knowledge. PS: non-pharmacological interventions. LvO: PET imaging. DB: neurobiology of treatment effects. All coauthors: critical review of the entire manuscript.

                Correspondence to Dr Emeran A Mayer; emayer@ 123456ucla.edu , EMayer@ 123456mednet.ucla.edu
                Article
                NIHMS1043705
                10.1136/gutjnl-2019-318308
                6999847
                31175206
                f64207d7-4685-4d39-97d6-5f58204fbeef

                Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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                Gastroenterology & Hepatology
                Gastroenterology & Hepatology

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