Abdominal Pain, the Adolescent and Altered Brain Structure and Function

<div><p>Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal.</p></div

Summary of Group Differences in Cortical Thickness.

<p>Summary of Group Differences in Cortical Thickness.</p

Brain Areas Showing Significant Associations between Cortical Thickness and Impact of GI-specific Symptoms on Health-related Quality of Life.

<p>Brain areas showing changes in cortical thickness that were associated with Total Symptoms scores from the PedsQL GI Symptoms Module rendered onto an inflated averaged study-specific brain for the left (lateral and medial views) and right hemisphere (medial view only) with corresponding scatter plots for selected significant clusters. For the PedsQL GI Symptoms Module (Total Symptom scores), greater reported HRQOL and lower GI-specific symptoms were associated with cortical thinning in the right (R) posterior cingulate cortex (PCC), left (L) anterior insula (aINS), L superior temporal sulcus (STS), and L fusiform gyrus.</p

Cortical Thickness and Disease Duration in Pediatric IBS Patients.

<p>Brain areas showing a significant relationship between cortical thickness and disease duration rendered onto an inflated averaged study-specific brain for the left (L) and right (R) hemispheres (lateral and medial views) with corresponding scatter plots for selected clusters. Top panel: Longer disease durations (yrs) were correlated with cortical thickening (warm colors) in the L and R DLPFC, and L supramarginal gyrus. In contrast, cortical thinning (cool colors) in the R lingual gyrus was correlated with disease durations in IBS patients. Bottom panel: Scatter plots illustrating positive and negative correlations between cortical thickness values (mm) for significant clusters and duration of IBS symptoms.</p

Individual Patient Characteristics.

<p>Individual Patient Characteristics.</p

Group Effects for Cortical Thickness.

<p>Brain areas showing group differences in cortical thickness rendered onto the right hemisphere (medial and lateral view) of a semi-inflated averaged brain. Pediatric patients with IBS, compared to healthy cohorts, showed cortical thickening in the right posterior cingulate cortex (PCC) and cortical thinning in the right posterior parietal cortex (PPC), dorsomedial (DMPFC) and dorsolateral (DLPFC) prefrontal cortices.</p

Descriptives for Psychometric and Clinical Measures in IBS Patients.

<p>Descriptives for Psychometric and Clinical Measures in IBS Patients.</p

Summary of Significant Clusters for Brain Areas Showing a Relationship between Cortical Thickness, Disease Duration and Pain Intensity.

<p>Summary of Significant Clusters for Brain Areas Showing a Relationship between Cortical Thickness, Disease Duration and Pain Intensity.</p

Group Effects for the Seed-based Functional Connectivity Analysis for the Posterior Cingulate Cortex.

<p>Seed-to-voxel whole-brain resting-state functional connectivity (RS-FC) results in pediatric IBS patients versus healthy controls for the left posterior cingulate cortex (PCC) seed rendered onto a semi-inflated brain showing cluster-corrected voxels (left panel) and the same cluster displayed in volume space rendered onto a semi-inflated glass brain (right panel) for the (A) dorsolateral prefrontal cortex (DLPFC) and the (B) parietal operculum. Statistical T maps showing results for RS-FC analysis for the PCC seed rendered onto the averaged study-specific brain (C). Hot voxels represent areas showing increased functional connectivity in patients relative to controls (Patients > Controls) for the PCC-DLPFC, whereas cool voxels represent decreased functional connectivity in patients versus controls for the PCC-Parietal Operculum (Controls > Patients).</p

Summary of Group Effects for Seed-based Functional Connectivity Analysis.

<p>Summary of Group Effects for Seed-based Functional Connectivity Analysis.</p