Interaction of psychological, physiological and neuronal processes in functional dyspepsia

Abstract

Functional dyspepsia is characterized by postprandial fullness, early satiation, epigastric pain, bloating, and nausea symptoms in the absence of structural changes in the gastrointestinal tract. Numerous works have been performed to identify the peripheral characteristics of functional dyspepsia and its association with dyspeptic symptoms, including changes of gastric motility, visceral sensitivity, secretion of hormones, functions of immune system. However, the pathophysiological mechanisms involved and standard treatment strategies are still lacking. The role of the dysfunction of the brain-gut axis and the effect of the food ingestion in the gastrointestinal symptoms of functional dyspepsia patients have therefore been attracting more interest in recent years. How the food is processed differently in the peripheral and in the central nervous system in functional dyspepsia has, however, received little attention in comparison to other functional gastrointestinal disorders. In this thesis, we used various approaches to examine the physiological and neuronal mechanisms in functional dyspepsia patients. We commenced by summarizing previous functional neuroimaging studies to establish their limitations. To bridge the resulting research gap, we investigated physiological and attentional responses to visual food cues, and measured the altered brain activity before and after the food ingestion in functional dyspepsia patients. In the paper I, we reviewed the current status of brain research related to functional dyspepsia and were able to clearly show a knowledge gap regarding neural mechanisms of food-related factors in functional dyspepsia patients. In paper II, we introduced how to design the neuroimaging study and interpret the results of it to clinicians. In paper III, we report findings of an eyetracking and behavioral study on functional dyspepsia patients. The patients showed 1) greater dyspeptic symptoms even after ingestion of a lower calorie and food intake from standard breakfast; 2) decreased pleasantness ratings to food images; and 3) reduced visual attention to food images in comparison to healthy controls. In paper IV, we report findings of a functional magnetic resonance imaging study during meal ingestion (yoghurt with different fat content and label info) in functional dyspepsia patients. The patients showed 1) greater abdominal pain, burning, and discomfort after high fat labeled yogurt ingestion than after low fat labeled yogurt ingestion irrespective of fat content, 2) increased activity in occipital areas before and after ingestion irrespective of fat content and label and increased activity in the middle frontal gyrus before ingestion, 3) increased functional connectivity between the insula and the precuneus after ingestion of yogurt with low fat label, and 4) greater nausea-related increased functional connectivity between the insula and the occipital gyrus after ingestion of high fat yogurt than of low fat yogurt. Furthermore, bidirectional influences between quality of life and depression, as mediated by dyspeptic symptoms and the impact of food craving on the amplitude of brain activity in the middle frontal gyrus, as mediated by depression in functional dyspepsia patients were recorded. In conclusion, the abnormal dietary behavior, reduced positive emotional response and visual attention to food images, and the role of cognitive perception of fat on the aggravation of dyspeptic symptoms should be considered in clinics and in research for functional dyspepsia.