title: Differential brain responses to gradual intragastric nutrient infusion and gastric balloon distension: A role for gut peptides?
abstract: Rapid gastric balloon distension to discomfort threshold activates the "pain neuromatrix" and deactivates exteroceptive sensory and "default mode network" regions. However, little is known about brain mechanisms underlying tolerance of meal-induced gastric distension. We aimed to directly compare brain responses to gradual balloon distension and intragastric nutrient infusion and to explore the role of differential gut peptide release in these responses.
  
  
  
  Brain responses to balloon- and nutrient-induced distension (to individually titrated pain or maximal satiation threshold) were measured in 15 healthy volunteers using H215O-PET on 2 separate days in counterbalanced order. The effects of increasing gastric distension and plasma levels of ghrelin and peptide YY3-36(PYY3-36) on neural activity were assessed.
  
  
  
  Balloon distension progressively activated pain-responsive regions and deactivated exteroceptive sensory and "default mode network" areas. During nutrient infusion, "pain neuromatrix" regions and the orbitofrontal cortex were progressively deactivated, while the midbrain was activated. Plasma levels of PYY3-36and ghrelin increased and decreased, respectively, during nutrient infusion only; decreasing ghrelin levels correlated with increasing midbrain activity.
  
  
  
  Different brain responses to gastric balloon distension and intragastric nutrient infusion are associated with nutrient-induced gut-brain signals, particularly to the midbrain, where these signals may interfere with both descending pain modulatory and mesolimbic reward processes. Deactivation of the "pain neuromatrix" during nutrient infusion may constitute the neurophysiological mechanism underlying the tolerance of normal meal volumes in health without induction of (painful) symptoms. Nutrient-induced deactivation of the orbitofrontal cortex may represent a key interoceptive meal termination signal.
authors.affiliation: Laboratory for Brain-Gut Axis Studies (LABGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium. Electronic address: huynhgiao.ly@med.kuleuven.be.
authors.forename: Huynh Giao
authors.initials: HG
authors.lastname: Ly
authors.affiliation: Laboratory for Cognitive Neurology, Division of Experimental Neurology, Department of Neurosciences, University of Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Laboratory for Brain-Gut Axis Studies (LABGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Depoortere
authors.affiliation: Laboratory for Brain-Gut Axis Studies (LABGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Laboratory for Brain-Gut Axis Studies (LABGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium; Consultation-Liaison Psychiatry, University Psychiatric Centre KU Leuven, Campus Gasthuisberg, University of Leuven, Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D005260:Female; D015905:Gastric Balloon; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D065812:Interoception / Q000502:physiology*; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000502:physiology*; D058748:Pain Perception / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood*; D019894:Peptide YY / Q000097:blood*; D049268:Positron-Emission Tomography / Q000379:methods*; D012527:Satiation / Q000502:physiology; D013270:Stomach / Q000502:physiology*; D055815:Young Adult
chemical_list: D054439:Ghrelin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)
keywords: Ghrelin; Gut-brain axis; Midbrain; Nutrient tolerance; Pain neuromatrix