Abstract

Abstract Background Crohn’s disease (CD) and its comorbidities may be associated with a specific intrinsic neural phenotype that can be measured using resting state functional connectivity (RSFC). RSFC alterations have been reported in CD in remission but have not been investigated in the active phase of the disease. Here, the primary aim was to study the effects of active CD on resting state networks (RSNs), hence identifying RSFC alterations specific to active CD status. A second aim was to investigate associations between disease duration and abdominal pain with RSFC in active CD. Methods 25 active CD patients and 25 age-, BMI- and gender-matched healthy controls (HC) were recruited. Active disease was defined as CRP > 5 mg/dl, or faecal calprotectin (FCP) >250 μg/g or through ileocolonoscopy or MRE. RsfMRI datasets were acquired on a 3T Philips Achieva scanner, with data corrected for physiological noise and motion. ICA analysis was carried out using MELODIC (FSL software). A multi-session temporal concatenation was used to generate 30 independent component (IC) maps of RSNs. A dual regression analysis with variance normalization, using group IC maps from HC group as the network template, was performed. Differences in RSN between HCs and CD patients and associations with covariates of interest were assessed. Results RSNs comprising the visual, cerebellar, frontal parietal and frontal RSN, default mode network (DMN), salience, temporal and dorsal attention RSN were identified. Enhancement of activity and increase connectivity in the medial visual RSN (orbital frontal cortex), in the frontal parietal network (occipital fusiform gyrus, thalamus, caudate, posterior cingulate cortex, postcentral gyrus) were observed in CD relative to HC. Further, decreased activity was seen in the salience network (cerebellum, postcentral gyrus), cerebellar network (occipital fusiform gyrus, cerebellum) and the DMN (parahippocampal gyrus, cerebellum) in CD relative to HC. Greater abdominal pain scores were associated with lower connectivity in the precuneus in the medial visual RSN, in the parietal operculum in the salience RSN, as well as reduced connectivity in the cerebellum in the frontal RSN. Finally, greater disease duration was associated with greater connectivity in the visual RSN in the middle temporal gyrus and planum temporale. Conclusion Alterations in RSFC between active CD and HC in RSNs implicated in cognition, attention, emotion and pain may reflect neuroplasticity in response to chronic systemic inflammation, abdominal pain, disease duration and severity. Identification of a neural phenotype specific to active CD status, may help guide intervention constituting a neurobehavioural precision medicine approach to treatment.

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