Elsevier

NeuroImage

Volume 39, Issue 4, 15 February 2008, Pages 1824-1831
NeuroImage

Gastric distention activates satiety circuitry in the human brain

https://doi.org/10.1016/j.neuroimage.2007.11.008Get rights and content

Abstract

Gastric distention during meal ingestion activates vagal afferents, which send signals from the stomach to the brain and result in the perception of fullness and satiety. Distention is one of the mechanisms that modulates food intake. We measured regional brain activation during dynamic gastric balloon distention in 18 health subjects using functional magnetic resonance imaging and the blood oxygenation level-dependent (BOLD) responses. The BOLD signal was significantly changed by both inflow and outflow changes in the balloon's volume. For lower balloon volumes, water inflow was associated with activation of sensorimotor cortices and right insula. The larger volume condition additionally activated left posterior amygdala, left posterior insula and the left precuneus. The response in the left amygdala and insula was negatively associated with changes in self-reports of fullness and positively with changes in plasma ghrelin concentration, whereas those in the right amygdala and insula were negatively associated with the subject's body mass index. The widespread activation induced by gastric distention corroborates the influence of vagal afferents on cortical and subcortical brain activity. These findings provide evidence that the left amygdala and insula process interoceptive signals of fullness produced by gastric distention involved in the controls of food intake.

Introduction

Multiple internal feedback signals influence food intake including gut-secreted peptides that provide information to the brain to inhibit feeding and terminate meal consumption (Blundell and Gillett, 2001, Cummings et al., 2002). Many of these signals are conveyed to the brainstem and hypothalamus via the vagus nerve (Hellstrom et al., 2004, Schwartz and Moran, 1996). Reduced neuronal sensitivity to these signals could result in unrestrained eating and obesity (Powley, 2000).

One of the key satiation mechanisms is gastric distention during food intake. Positron emission tomography (PET) with [O-15]water (Ladabaum et al., 2001, Stephan et al., 2003, Vandenbergh et al., 2005) or functional magnetic resonance imaging (fMRI) with blood oxygenation level-dependent (BOLD) contrast (Ladabaum et al., 2007, Lu et al., 2004) method have been used to examine brain activation during gastric distention. In these studies, a balloon was orally placed in the stomach and its volume was suddenly enlarged to a feeling of fullness that elicited pain (however, during normal food intake gastric distension is gradual and not painful), activating several brain regions, including the anterior insula and somatosensory cortices, but not the amygdala.

The amygdala might have an important role in feeding behavior. Amygdala lesions in animals (Rollins and King, 2000) or humans (King, 2006) lead to hyperphagia and excessive weight gain, and neuroimaging studies have demonstrated that food-related stimuli, tastes and odors activate the amygdala (Del Parigi et al., 2002, O'Doherty et al., 2002, Gottfried et al., 2003, Small et al., 2005, Smeets et al., 2006).

Here we aimed to study the brain response during the gradual gastric distention produced by moderate food intake in order to better understand the mechanisms underlying normal and abnormal eating behavior. We used the gastric balloon distention procedure developed by Geliebter (1988), which has been used to assess changes in fullness and to test meal intake as well as to measure human gastric capacity in subjects with bulimia nervosa and binge eating disorders (Geliebter and Hashim, 2001, Geliebter et al., 1992, Geliebter et al., 2004). In this procedure, the balloon is filled with water warmed to normal body temperature (37 °C). This method mimics better the gastric distention during food intake more closely than methods used in prior fMRI studies (Ladabaum et al., 2007, Lu et al., 2004). Furthermore, while previous fMRI studies used sudden volume changes to assess fullness and pain sensations, we changed the balloon volume slowly to study the brain response to a slow stomach distension that mimics normal food intake. We hypothesized that the involvement of the amygdala in feelings of fullness could be demonstrated using fMRI and this gradual and not painful gastric distension paradigm that mimics normal food intake.

Section snippets

Subjects

Three female and 15 male healthy subjects (32.0 ± 6.6 years of age, range 22–47 years old) all with body mass index (BMI) lower than 30 (kg/m2) participated in the study. All subjects gave written informed consent after the experimental procedure was explained and after they had read the Consent form approved by the Institutional Review Boards at Brookhaven National Laboratory and State University of New York-Stony Brook. The exclusion criteria of the study were urine positive for psychoactive

Rating scores of self-report questionnaire

The range of body mass index (BMI) for these 18 subjects was 20–29 (mean: 24.4 ± 3.0). The rating score data sets of 3 subjects were lost due to data acquisition problems. During the gastric distention paradigm (Fig. 1), we obtained self-reported ratings of fullness, discomfort, hunger and desire for food during the empty (0 ml) and full (500 ml) balloon conditions for the remaining 15 subjects. Each of the ratings was averaged across the fMRI runs. Fullness sensation was significantly higher

Discussion

Here we show that non-painful proximal gastric distension activated the posterior insula, left posterior amygdala and sensorimotor cortices. The activation in these regions is compatible with those reported by studies on gastric sensation (Stephan et al., 2003) and is therefore likely to reflect the sensation of the stomach in response to the dynamic volume changes of the balloon.

Acknowledgments

This research was carried out at Brookhaven National Laboratory (BNL) under support by the U.S. Department of Energy OBER (DE-ACO2-76CH00016), the National Institute on Drug Abuse (DA7092, DA00280 and DK072011), the National Institute of Diabetes and Digestive and Kidney Diseases (DK072011), the National Institute on Alcohol Abuse and Alcoholism (AA9481 and Y1AA3009) and by the GCRC at University Hospital Stony Brook (NIH MO1RR 10710). We thank B. Hubbard, H.-D. Lee and M. Jayne for patient

References (49)

  • U. Ladabaum et al.

    Gastric distention correlates with activation of multiple cortical and subcortical regions

    Gastroenterology

    (2001)
  • U. Ladabaum et al.

    Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: a functional magnetic resonance imaging study

    NeuroImage

    (2007)
  • J.P. O'Doherty et al.

    Neural responses during anticipation of a primary taste reward

    Neuron

    (2002)
  • C. Owyang

    Negative feedback control of exocrine pancreatic secretion: role of cholecystokinin and cholinergic pathway

    J. Nutr.

    (1994)
  • G.J. Schwartz et al.

    Sub-diaphragmatic vagal afferent integration of meal-related gastrointestinal signals

    Neurosci. Biobehav. Rev.

    (1996)
  • D.M. Small et al.

    Differential neural responses evoked by orthonasal versus retronasal odorant perception in humans

    Neuron

    (2005)
  • P.A. Smeets et al.

    Effect of satiety on brain activation during chocolate tasting in men and women

    Am. J. Clin. Nutr.

    (2006)
  • A. Solomon et al.

    The nucleus tractus solitari (NTS) participates in peripheral ghrelin glucostatic hunger signalling mediated by insulin

    Neuropeptides

    (2006)
  • E. Stephan et al.

    Functional neuroimaging of gastric distention

    J. Gastrointest. Surg.

    (2003)
  • D. Tomasi et al.

    fMRI-acoustic noise alters brain activation during working memory tasks

    NeuroImage

    (2005)
  • J. Vandenbergh et al.

    Regional brain activation during proximal stomach distention in humans: a positron emission tomography study

    Gastroenterology

    (2005)
  • T. Zhang et al.

    Neural regulation of peptide YY secretion

    Regul. Pept.

    (1993)
  • T.W. Bailey et al.

    Cranial visceral afferent pathways through the nucleus of the solitary tract to caudal ventrolateral medulla or paraventricular hypothalamus: target-specific synaptic reliability and convergence patterns

    J. Neurosci.

    (2006)
  • K. Bielefeldt et al.

    Basic and clinical aspects of visceral sensation: transmission in the CNS

    Neurogastroenterol. Motil.

    (2005)
  • Cited by (0)

    View full text