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Title: Altered brain structure and functional connectivity and its relation to pain perception in girls with irritable bowel syndrome

item BHATT, RAVI - University Of California (UCLA)
item GUPTA, ARPANA - University Of California (UCLA)
item LABUS, JENNIFER - University Of California (UCLA)
item ZELTZER, LONNIE - University Of California (UCLA)
item TSAO, JENNIE - University Of California (UCLA)
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item TILLISCH, KIRSTEN - University Of California (UCLA)

Submitted to: Psychosomatic Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2019
Publication Date: 2/1/2019
Citation: Bhatt, R.R., Gupta, A., Labus, J.S., Zeltzer, L.K., Tsao, J.C., Shulman, R.J., Tillisch, K. 2019. Altered brain structure and functional connectivity and its relation to pain perception in girls with irritable bowel syndrome. Psychosomatic Medicine. 81(2):146-154.

Interpretive Summary: Approximately 15% of children and adults worldwide suffer from pain associated with functional gastrointestinal disorders such as irritable bowel syndrome. There is growing appreciation that there may be differences in brain function between those with/without irritable bowel. In this study we carried out functional magnetic resonance imaging (fMRI) studies in a group of girls with and without irritable bowel syndrome. We found that there were differences in brain volume in different regions of the brain between the two groups. In addition, the connectedness between brain regions differed. These findings are similar to those in adults. This means that these structural changes in the brain occur early in development. These results are important and highlight that girls may experience various levels of pain associated with irritable bowel and different strategies, including dietary approaches, are needed.

Technical Abstract: Imaging studies in adults with irritable bowel syndrome (IBS) have shown both morphological and resting state (RS) functional connectivity (FC) alterations related to cortical modulation of sensory processing. Because analogous differences have not been adequately investigated in children, this study compared gray matter volume (GMV) and RS-FC between girls with IBS and healthy controls (HC) and tested the correlation between brain metrics and laboratory-based pain thresholds (Pth). Girls with Rome III criteria IBS (n = 32) and matched HCs (n = 26) were recruited. In a subset of patients, Pth were determined using a thermode to the forearm. Structural and RS scans were acquired. A voxel-based general linear model, adjusting for age, was applied to compare differences between groups. Seeds were selected from regions with group GMV differences for a seed-to-voxel whole brain RS-FC analysis. Significance for analyses was considered at p < .05 after controlling for false discovery rate. Significant group differences were correlated with Pth. Girls with IBS had lower GMV in the thalamus, caudate nucleus, nucleus accumbens, anterior midcingulate (aMCC), and dorsolateral prefrontal cortex. They also exhibited lower RS-FC between the aMCC and the precuneus, but greater connectivity between the caudate nucleus and precentral gyrus. Girls with IBS had higher Pth with a moderate effect size (t(22.81) = 1.63, p = .12, d = 0.64) and lower thalamic GMV bilaterally was correlated with higher Pth (left: r = -.62, p(FDR) = .008; right: r = -.51, p(FDR) = .08). Girls with IBS had lower GMV in the PFC, basal ganglia, and aMCC, as well as altered FC between multiple brain networks, suggesting that structural changes related to IBS occur early in brain development. Girls with IBS also showed altered relationships between pain sensitivity and brain structure.