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      Multimodal Brain MRI of Deep Gray Matter Changes Associated With Inflammatory Bowel Disease

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          Abstract

          Background

          Behavioral symptoms, including mood disorders, substantially impact the quality of life of patients with inflammatory bowel disease (IBD), even when clinical remission is achieved. Here, we used multimodal magnetic resonance imaging (MRI) to determine if IBD is associated with changes in the structure and function of deep gray matter brain regions that regulate and integrate emotional, cognitive, and stress responses.

          Methods

          Thirty-five patients with ulcerative colitis (UC) or Crohn’s disease (CD) and 32 healthy controls underwent 3 Tesla MRIs to assess volume, neural activity, functional connection strength (connectivity), inflammation, and neurodegeneration of key deep gray matter brain regions (thalamus, caudate, pallidum, putamen, amygdala, hippocampus, and hypothalamus) involved in emotional, cognitive and stress processing. Associations with sex, presence of pain, disease activity, and C-reactive protein (CRP) concentration were examined.

          Results

          Significantly increased activity and functional connectivity were observed in cognitive and emotional processing brain regions, including parts of the limbic system, basal ganglia, and hypothalamus of IBD patients compared with healthy controls. Inflammatory bowel disease patients exhibited significantly increased volumes of the amygdala and hypothalamus, as well as evidence of neurodegeneration in the putamen and pallidum. Hippocampal neural activity was increased in IBD patients with active disease. The volume of the thalamus was positively correlated with CRP concentration and was increased in females experiencing pain.

          Conclusions

          Patients with IBD exhibit functional and structural changes in the limbic and striatal systems. These changes may be targets for assessing or predicting the response to therapeutic interventions aimed at improving comorbid emotional and cognitive symptoms.

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          Most cited references58

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          Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks.

          Resting state functional connectivity reveals intrinsic, spontaneous networks that elucidate the functional architecture of the human brain. However, valid statistical analysis used to identify such networks must address sources of noise in order to avoid possible confounds such as spurious correlations based on non-neuronal sources. We have developed a functional connectivity toolbox Conn ( www.nitrc.org/projects/conn ) that implements the component-based noise correction method (CompCor) strategy for physiological and other noise source reduction, additional removal of movement, and temporal covariates, temporal filtering and windowing of the residual blood oxygen level-dependent (BOLD) contrast signal, first-level estimation of multiple standard functional connectivity magnetic resonance imaging (fcMRI) measures, and second-level random-effect analysis for resting state as well as task-related data. Compared to methods that rely on global signal regression, the CompCor noise reduction method allows for interpretation of anticorrelations as there is no regression of the global signal. The toolbox implements fcMRI measures, such as estimation of seed-to-voxel and region of interest (ROI)-to-ROI functional correlations, as well as semipartial correlation and bivariate/multivariate regression analysis for multiple ROI sources, graph theoretical analysis, and novel voxel-to-voxel analysis of functional connectivity. We describe the methods implemented in the Conn toolbox for the analysis of fcMRI data, together with examples of use and interscan reliability estimates of all the implemented fcMRI measures. The results indicate that the CompCor method increases the sensitivity and selectivity of fcMRI analysis, and show a high degree of interscan reliability for many fcMRI measures.
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            Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

            In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.
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              Inflammatory bowel disease: clinical aspects and established and evolving therapies.

              Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies--including biological therapies--directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways. Finally, we summarise the practical aspects of standard therapies including dosing, precautions, and side-effects.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Inflammatory Bowel Diseases
                Oxford University Press (OUP)
                1078-0998
                1536-4844
                May 19 2022
                May 19 2022
                Affiliations
                [1 ]Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
                [2 ]Department of Radiology, University of Calgary, Calgary, Alberta, Canada
                [3 ]Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
                [4 ]The Seaman Family MR Research Centre, University of Calgary, Calgary, Alberta, Canada
                [5 ]The Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
                [6 ]Department of Medicine, University of Calgary, Calgary, Alberta, Canada
                [7 ]The Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
                [8 ]From the *Department of Medicine, University of Calgary, Calgary, Alberta, Canada
                [9 ]Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada
                [10 ]The Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
                Article
                10.1093/ibd/izac089
                35590449
                77c35675-223f-49c7-85ae-0f853064d604
                © 2022

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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