Structural Imaging Changes and Behavioral Correlates in Patients with Crohn's Disease in Remission

Abstract

Background: Crohn's disease (CD) is a subtype of inflammatory bowel disease caused by immune-mediated inflammation in the gastrointestinal tract. The extent of morphologic brain alterations and their associated cognitive and affective impairments remain poorly characterized. Aims: We used magnetic resonance imaging to identify structural brain differences between patients with Crohn's disease in remission compared to age-matched healthy controls and evaluated for structural-behavioral correlates. Methods: Nineteen patients and 20 healthy, age-matched controls were recruited in the study. Group differences in brain morphometric measures and correlations between brain measures and performance on a cognitive task, the verbal fluency (VF) task, were examined. Correlations between brain measures and cognitive measures as well as self-reported measures of depression, personality, and affective scales were examined. Results: Patients showed significant cortical thickening in the left superior frontal region compared to controls. Significant group differences were observed in sub-cortical volume measures in both hemispheres. Investigation of brain-behavior correlations revealed significant group differences in the correlation between cortical surface area and VF performance, although behavioral performance was equivalent between the two groups. The left middle temporal surface area was a significant predictor of VF performance with controls showing a significant positive correlation between these measures, and patients showing the opposite effect. Conclusion: Our results indicate key differences in structural brain measures in patients with CD compared to controls. Additionally, correlation between brain measures and behavioral responses suggest there may be a neural basis to the alterations in patients' cognitive and affective responses.

Keywords: Crohn’s disease; cortical thickness; gut-brain axis; neuroimaging.

FIGURE 1

Increase in cortical thickness (warm colors) in the left hemisphere (A – medial and lateral surfaces) and right hemisphere (B – lateral and medial surfaces) in patients compared to healthy controls. All vertices with threshold between 0.01 < p < 0.0001, uncorrected, shown for display purposes. (C) Inset shows the cluster in the left hemisphere superior frontal region that survived correction for multiple comparisons, p < 0.05. Blue–cyan represents cortical thinning; red represents cortical thickening.

FIGURE 2

Increase in cortical surface area (warm colors) in the left hemisphere (A – medial and lateral surfaces) and right hemisphere (B – lateral and medial surfaces) in patients compared to healthy controls. All vertices with threshold between 0.01 < p < 0.0001, uncorrected, shown for display purposes.

FIGURE 3

(A) Regional cortical surface areas showing significant group differences in the correlation between the left cortical surface area and normed verbal fluency scores. Left precentral (p = 0.008) and middle temporal regions (p = 0.002) showed significant effects (corrected for multiple comparisons). Blue-cyan represents negative association; red represents positive association. (B) Graphs showing correlation between cortical surface area (mm²) for the left middle temporal region and verbal fluency performance for controls (left) and patients (right). Dotted lines represent 95% confidence interval (CI) for the mean. The left middle temporal surface area was the most significant predictor of performance with standardized coefficient β = 0.90, p = 0.005; left precentral area only showed a trend toward significance with β = -0.496, p = 0.09 and is therefore not shown here.