Huynh Giao Ly1, Patrick Dupont2, Koen Van Laere3, Inge Depoortere4, Jan Tack4, Lukas Van Oudenhove5. 1. 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. 2. Laboratory for Cognitive Neurology, Division of Experimental Neurology, Department of Neurosciences, University of Leuven, Leuven, Belgium. 3. Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium. 4. 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. 5. 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.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 PYY3-36 and ghrelin increased and decreased, respectively, during nutrient infusion only; decreasing ghrelin levels correlated with increasing midbrain activity. CONCLUSION: 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.
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 PYY3-36 and ghrelin increased and decreased, respectively, during nutrient infusion only; decreasing ghrelin levels correlated with increasing midbrain activity. CONCLUSION: 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: Karen Van den Houte; Premysl Bercik; Magnus Simren; Jan Tack; Stephen Vanner Journal: Am J Gastroenterol Date: 2022-05-04 Impact factor: 12.045