Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes - An fMRI study

BACKGROUND: To evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD). METHODS: Thirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI. RESULTS: During intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (P = 0.008 and P = 0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (P = 0.008) and peak time (P < 0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion. CONCLUSIONS: The four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.