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Functional gastrointestinal disorders (FGIDs) affect an extensive population and bring along high costs. Various alterations in perception of visceral stimuli have been reported in these patients, and previous research has recently demonstrated the ability of fear learning to alter perception of exteroceptive stimuli. The aim of this study was to learn more about the effect of associative fear learning on perception of visceral stimuli in general and visceral discrimination in particular. As literature on the just-noticeable difference thresholds for visceral sensations is lacking, a pilot was performed to identify variations in just-noticeable difference. Next, in the actual experiment, changes in discrimination acuity were assessed after differential interoceptive fear conditioning. We adopted a set of 2 hardly discriminable esophageal balloon stimuli as conditioned stimuli (CSs). During a conditioning phase, one of these was always followed by a noxious electrical stimulus (unconditioned stimulus (US)), while the other one was never followed by the US. A 3 alternative-forced choice ask was used to investigate how well participants discriminated between both CSs before and after conditioning. Galvanic skin responses and subjective ratings suggest no differential fear learning occurred. Taken together, the results indicate that our manipulation did not succeed and therefore the relation between fear conditioning and visceral discrimination remains unclear. Recommendations for future research addressing this topic will be given.

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Background: Chronic fatigue syndrome (CFS) is characterized by persistent fatigue that does not improve with rest. Previous studies showed an association between reduced heart rate variability (HRV) and CFS symptoms, but the link between HRV during a cognitive task and self-reported symptoms in CFS patients compared to healthy controls (HC) has not intensively been investigated yet. Next, it is unknown whether symptoms reported by CFS patients during laboratory (lab) assessments reflect their everyday experiences. Objectives: We compared symptom experience between CFS patients and HC in their daily lives and in a lab setting, and determined to which extent lab-based assessments of CFS symptoms reflect the real-life experiences of individuals. We explored the link between HRV during the Paced Auditory Serial Attention Task (PASAT) and self-reported symptoms, we studied whether there is a difference between HRV at rest and during the PASAT across all participants, and we compared HRV at rest and during the PASAT between CFS patients and HC. Methods: Five CFS patients, who fulfilled the 1994 Fukuda criteria, and seven HC were included. All participants reported symptoms using the Experienced Sampling Methodology, underwent a HRV recording at rest and during the PASAT and performed the Maastricht Acute Stress Test, the PASAT, and the cycling task in the lab. Subjective stress in the lab was measured via a Visual Analogue Scale and feelings of both mental and physical fatigue in the lab were collected via the Fatigue and Energy Scale. Nonparametric analyses compared CFS symptoms between CFS patients and HC in their daily lives and in the lab, as well as the HRV at rest and during the PASAT between both groups, and between HRV at rest and during the PASAT across all participants. Correlation analyses evaluated if lab-based assessments reflect the real-life experiences of CFS symptoms, and assessed the link between HRV and symptom severity. Results: CFS patients differed significantly from HC in their experiences of physical and mental fatigue/exhaustion, and cognitive problems in their daily lives and in the lab. While the experience of energy loss was only significantly different between both groups in the lab, the experience of brain fog and stress differed significantly between both groups in their daily lives. Correlation analyses did not reveal any significant effects on the experience of CFS symptoms in participants' daily life versus in the lab. CFS patients and HC differed significantly in HRV during the PASAT.   The correlation analyses demonstrated a significant inverse relationship between resting HRV as well as during the PASAT and mental fatigue/exhaustion and cognitive problems. However, brain fog was only substantially negatively associated with HRV during the PASAT. Conclusion: CFS symptoms are significantly more pronounced in CFS patients compared to HC, both in their daily lives as in the lab. There are no significant differences between both groups in how they responded to a physical, cognitive or stressful task. Our results suggest that daily life symptoms may not be fully captured by lab-based assessments. No significant difference was found between HRV at rest and HRV during the PASAT. CFS patients had significantly lower HRV during the PASAT than HC, and we observed a significant inverse correlation between HRV and symptom severity across all participants. Further research is needed to confirm or deny our observations.

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Introduction: Irritable bowel syndrome (IBS) is an impairing and highly prevalent gut brain axis disorder. The etiology isn’t fully understood, but dysfunction of the stress response system has been proposed as pathophysiological mechanism. However, previous studies investigating the IBS stress response obtained conflicting results. The high comorbidity rate in IBS could explain this ambiguity, as alterations in the stress response have also been seen in anxiety, depression, fibromyalgia and chronic fatigue syndrome (CFS), four of the most common comorbidities in IBS. Objective: The aim of this study is to investigate the differences in neuroendocrine stress response between IBS and comorbid IBS, by looking at the hypothalamic–pituitary–adrenal (HPA) axis cortisol level and neural (de)activations in response to a psychosocial stressor. Methods: Participants had to fulfill the ROME IV-criteria to participate and were categorized in the IBS-comorbid group if criteria were met for current depression, anxiety disorder, fibromyalgia and/or CFS. Nineteen participants (nIBS-alone= 9, nIBS-comorbid= 10) performed the Maastricht Acute Stress Test (MAST). Saliva samples were collected and further analyzed by performing an enzyme-linked immunosorbent assay (ELISA). Thirteen participants (nIBS-alone= 6, nIBS-comorbid= 7) performed the Montreal Imaging Stress Task (MIST) in an MRI scanner. Subjective stress was measured by using Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS) in respectively the MAST and the MIST. A whole brain general linear model was used to analyze the MIST fMRI data, more specifically a one sample t-test on the “stress vs. control” contrast (voxel level= puncorrected<0.001, cluster level= qFDR-corr<0.05 (50 voxels)) and a two sample t-test on the contrast “stress vs. control in IBS-alone vs. IBS-comorbid” (voxel level= puncorrected< 0.005, cluster level= qFDR-corr< 0.05 (50 voxels)). A marginal mixed model was used to analyze subjective stress and ELISA cortisol data (p<0.05). Results: Findings of the subjective stress analyses demonstrated statistical significance of the contrast “stress vs. no stress”, implicating effectiveness of the MAST and MIST at eliciting subjective stress. However, no significant difference was found in the contrast “stress vs. no stress in IBS-alone vs. IBS-comorbid”. The MIST fMRI results of the whole study population revealed significant activation of the right supramarginal gyrus, thalamus, right anterior insula (rAI), cerebellum, cingulate gyrus, right superior frontal gyrus in the contrast “stress>control”. Further, significantly greater activation in the rAI in the IBS-alone group compared to the IBS-comorbid group was seen (contrast= “stress vs. control in IBS-alone vs. IBS-comorbid”). The interaction effect “time x group” from the cortisol data analysis revealed no significant difference in cortisol response between IBS and comorbid IBS. Conclusion: We found a significant greater rAI activation in the contrast “stress vs. control in IBS-alone vs. IBS-comorbid” in response to the MIST. However, no significant difference in cortisol response was seen between the two groups in response to the MAST. To our knowledge is this the first study investigating this difference. Further research is needed to gain more insight in the mechanism underlying IBS-comorbidities, in order to improve the diagnosis, disease management and treatment options of IBS.

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Background: Low calorie sweeteners (LCS) are hypothesized to lower energy intake and might therefore be useful to help control obesity. However, the beneficial impact of these LCS on body weight remains controversial. Results from recent studies suggest that erythritol might be a good candidate substitute for sugar, as it may reduce energy intake without compensatory overeating or early return of hunger. However, its rewarding properties remain unknown. Aim: In this master thesis, we aimed to investigate erythritol’s sweet taste-related reward system responses in light of the newly discovered satiating effects. Hypothesis: We hypothesized that sucrose would elicit stronger reward system responses than sucralose, but did not formulate a specific hypothesis on erythritol given the lack of existing data. Methods: Thirty healthy males were scanned using functional magnetic resonance imaging (fMRI). Prior to scanning, we individually matched the concentrations of erythritol and sucralose to the perceived sweetness of a 10% sucrose solution. A triangle test was used to determine whether subjects were able to distinguish the solutions. On the day of the scan, participants first rated their hunger using a visual analogue scale (VAS) and the intensity of each solution using the General Intensity Scale (GIS). During the scan, participants received small sips of erythritol, sucrose, sucralose and water (negative control) in pseudorandomized order. After each delivery, they rated sweetness liking using the general hedonic liking scale (GHIS). Behavioral data were analyzed using linear mixed models. For the fMRI data, we performed a group-level univariate general linear model to test whether there were significant differences in brain responses between conditions within a mask of regions of interest. Results: Results from the triangle test indicated that people were able to distinguish at least one taste pair above the chance level. Sweetness intensity ratings for erythritol were significantly lower compared to sucrose (p = 0.0182) and sucralose (p <0.0001). Additionally, liking ratings for erythritol were significantly lower than those for sucrose and sucralose (p = 0.0041 respectively). When adjusting for the covariates hunger and sweetness intensity, the difference in liking ratings between erythritol and sucrose (p = 0.0037), and erythritol and sucralose (p = 0.0037) remained significant. Only intensity had a significant influence on the liking ratings (p = 0.0108), hunger did not (p = 0.9164). Analysis of the fMRI data did not reveal any significant differences in activation between the different sweetener conditions, but also not when comparing them with water. Conclusion: Erythritol, despite its sweet taste and satiating properties, evokes lower liking responses than sucrose and sucralose. We did not find any differences in brain responses between the different sweeteners, nor when comparing them with water.