Learned Fear of Gastrointestinal Sensations in Healthy Adults

Background & Aims Gastrointestinal symptom-specific fear and anxiety are important determinants of gastrointestinal symptom perception. We studied learning of fear toward innocuous gastrointestinal sensations as a putative mechanism in the development of gastrointestinal symptom-specific fear and anxiety. Methods Fifty-two healthy subjects (26 women) received 2 types of esophageal balloon distention at a perceptible but nonpainful intensity (conditioned stimulus [CS], the innocuous sensation) and at a painful intensity (unconditioned stimulus [US]). Subjects were assigned randomly to 1 of 2 groups. During the learning phase, the innocuous CS preceded the painful US in the experimental group (n = 26). In the control group (n = 26), on the contrary, the US never followed the CS directly. During a subsequent extinction phase, both groups received only CS distention—the painful US was no longer administered. Indexes of fear learning toward the innocuous CS distention included the skin conductance response, fear-potentiated startle (measured by the eye-blink electromyogram), and self-reported expectancy of the US. Results During the learning phase, only the experimental group learned to fear the innocuous gastrointestinal CS, based on the increase in US expectancy (compared with the control group, P = .04), increased skin conductance response (compared with the control group, P = .03), and potentiated startle reflex (compared with the control group, P = .001) in response to the CS. The differences between the experimental and control groups in US expectancy and skin conductance, but not fear-potentiated startle, disappeared during the extinction phase. Conclusions Fear toward innocuous gastrointestinal sensations can be established through associative learning in healthy human beings. This may be an important mechanism in the development of fear of gastrointestinal symptoms, implicated in the pathophysiology of functional gastrointestinal disorders

Brain-gut interactions in the regulation of visceral pain perception and food intake

The importance of bidirectional brain-gut communication in the regulation and dysregulation of many vital functions in both health and disease is increasingly being recognized. This so-called brain-gut axis constitutes the core neurobiological substrate regulating normal digestive processes in health, including appetite and food intake, and in integrating these processes with the overall physical and emotional state of the body. Dysfunction at any level of the brain-gut axis may result in aberrant processing and, thus, perception of physiological as well as noxious interoceptive signals and is therefore believed to play a major role in the generation of chronic unexplained gastrointestinal symptoms such as visceral pain and disorders of food intake including obesity. Despite intense scrutiny, the pathophysiology of these disorders remains incompletely understood, and even in health there is still much ambiguity. This is mostly due to the fact that research on both visceral pain and food intake regulation is still hampered by dualism, with some authors focusing on the brain and others on the periphery. The present doctoral project aimed to gain more insight into the mechanisms underlying processing and modulation of gut-brain signals in health as well as disorders of food intake. More specifically, we took an integrative approach to the study of visceral pain and food intake, combining several neurophysiological, psychological/behavioral and biochemical methods to investigate the interaction between central and peripheral mechanisms.nrpages: 102status: publishe

Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion

Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology ('comfort foods') and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression.status: publishe

Effect of acute Delta 9-tetrahydrocannabinol administration on subjective and metabolic hormone responses to food stimuli and food intake in healthy humans: a randomized, placebo-controlled study

BACKGROUND: The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans. OBJECTIVE: We aimed to investigate the effect of oral Δ9-tetrahydrocannabinol (THC) on subjective and metabolic hormone responses to visual food stimuli and food intake. METHODS: Seventeen healthy subjects participated in a single-blinded, placebo-controlled, 2 × 2 crossover trial. In each of the 4 visits, subjective "liking" and "wanting" ratings of high- and low-calorie food images were acquired after oral THC or placebo administration. The effect on food intake was quantified in 2 ways: via ad libitum oral intake (half of the visits) and intragastric infusion (other half) of chocolate milkshake. Appetite-related sensations and metabolic hormones were measured at set time points throughout each visit. RESULTS: THC increased "liking" (P = 0.031) and "wanting" ratings (P = 0.0096) of the high-calorie, but not the low-calorie images, compared with placebo. Participants consumed significantly more milkshake after THC than after placebo during oral intake (P = 0.0005), but not intragastric infusion, of milkshake. Prospective food consumption ratings during the food image paradigm were higher after THC than after placebo (P = 0.0039). THC also increased plasma motilin (P = 0.0021) and decreased octanoylated ghrelin (P = 0.023) concentrations before milkshake consumption (i.e., in both oral intake and intragastric infusion test sessions), whereas glucagon-like peptide 1 responses to milkshake intake were attenuated by THC during both oral (P = 0.0002) and intragastric (P = 0.0055) administration. CONCLUSIONS: These findings suggest that the ECS drives food intake by interfering with anticipatory, cephalic phase, and metabolic hormone responses. This trial was registered at clinicaltrials.gov as NCT02310347.status: publishe

The gut-brain axis in health neuroscience: implications for functional gastrointestinal disorders and appetite regulation

Over the past few years, scientific interest in the gut-brain axis (i.e., the bidirectional communication system between the gastrointestinal tract and the brain) has exploded, mostly due to the identification of the gut microbiota as a novel key player in this communication. However, important progress has also been made in other aspects of gut-brain axis research, which has been relatively underemphasized in the review literature. Therefore, in this review, we provide a comprehensive, although not exhaustive, overview of recent research on the functional neuroanatomy of the gut-brain axis and its relevance toward the multidisciplinary field of health neuroscience, excluding studies on the role of the gut microbiota. More specifically, we first focus on irritable bowel syndrome, after which we outline recent findings on the role of the gut-brain axis in appetite and feeding regulation, primarily focusing on the impact of subliminal nutrient-related gut-brain signals. We conclude by providing future perspectives to facilitate translation of the findings from gut-brain axis neuroscientific research to clinical applications in these domains.status: publishe