242 Brain Processing of Rectal Sensation in Children With Chronic Functional Constipation

Abstract

Background and Objective: The pathophysiology underlying pediatric chronic functional constipation (FC) is poorly understood. These children often report loss of sensation of urge to defecate. Functional magnetic resonance imaging (fMRI) studies have been used to unravel brain processing of visceral sensation in adults with functional gastrointestinal disorders. However, brain-imaging data are lacking in both adults and children with constipation. The aim is to investigate the cerebral activity in response to rectal distension in children with FC and in healthy controls (HCs). Methods: 15 patients with FC (8M/7F; mean age 14.3 yrs, range 12-18 yrs) and 15 HCs (6M/9F; mean age 20.1 yrs, range 18-21 yrs) participated. Rectal barostat was performed prior to the fMRI scan. A stepwise pressure-controlled distension protocol was used to determine the pressure threshold for urge sensation. Subjects received 2 sessions of 5 stimulations consisting of repetitions of 30 sec of rectal stimulation with previous defined pressure threshold, followed by 30 sec of rest during acquisition blood oxygenation level-dependent (BOLD) fMRI. Images were acquired on a 3Tesla MRI scanner with an 8-channel SENSE head receive coil. A T2*-weighted echo planar imaging sequence was acquired with: TR/TE=3000/30 ms, slice thickness=3.0 mm, voxel size=1.72 x 1.72 x 3 mm, with 40 axial slices, in ascending mode covering the whole brain. fMRI signal differences were analyzed using SPM8 in Matlab, thresholded at p<0.001. Cerebral activation was defined as BOLD increase during rectal distension and cerebral deactivation as BOLD decrease during rectal distension. Results: FC patients had higher thresholds for urgency than HCs (p<0.001). FC patients needed a mean pressure of 18.2 mmHg above MDP to provoke urge sensation, compared to a mean pressure of 8.6 mmHg above MDP in HCs. The groups were differentiated by both activated and deactivated regions in response to rectal distension. FC patients showed activation in the dorsolateral prefrontal cortex and deactivation in the median somatosensory cortex, insula and amygdala. HCs showed deactivation in the same areas, but in contrast, no regions showed significant activation in response to rectal distension. Conclusion: This is the first study evaluating cerebral processing of rectal sensation in constipated patients. FC patients and HCs had a different pattern of cerebral activation and deactivation during rectal distension, suggesting different neural processing of rectal urge sensation in brain regions previously implicated in adult studies using visceral pain stimuli.