TY - JOUR T1 - Neural indicators of human gut feelings JF - bioRxiv DO - 10.1101/2021.02.11.430867 SP - 2021.02.11.430867 AU - Ahmad Mayeli AU - Obada Al Zoubi AU - Evan J. White AU - Sheridan Chappelle AU - Rayus Kuplicki AU - Ryan Smith AU - Justin S. Feinstein AU - Jerzy Bodurka AU - Martin P. Paulus AU - Sahib S. Khalsa Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/13/2021.02.11.430867.abstract N2 - Understanding the neural processes that govern the human gut-brain connection has been challenging due to the inaccessibility of the body’s interior. In this study, we aimed to identify neural responses to gastrointestinal sensation (i.e., the neural basis of ‘gut feelings’) in healthy humans using a minimally invasive mechanosensory probe. Combining electroencephalography and electrogastrography with signal detection theory measures, we quantified brain, stomach, and perceptual (button-press) responses following the ingestion of a vibrating capsule. The relationship between vibration strength and perceptual sensitivity was evaluated using two stimulation conditions (normal and enhanced). Most individuals successfully perceived capsule stimulation in both conditions, as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster reaction time and reduced reaction time variability. Stomach stimulation induced responses in a cluster of parieto-occipital leads near the midline via a late positive potential emerging 300-600 milliseconds after stimulation onset. Moreover, these ‘gastric evoked potentials’ showed dose-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our findings are consistent with recent neurogastric and optogenetic studies demonstrating a role for posteromedial cortices in gastrointestinal interoception and body dissociation and highlight a unique form of enterically-focused sensory monitoring within the human brain. Overall, these results show that this minimally invasive approach could serve as a useful tool for understanding gut-brain interactions in healthy and clinical populations.Significance Statement The human brain continuously receives input from the stomach and intestines. These sensations are intuitively incorporated as ‘gut feelings’ into decision-making during daily life, yet we still know very little about how the brain processes gut signals. Here, we developed a minimally invasive approach to studying human gut feelings. In healthy individuals we found that an ingestible vibrating capsule produced reliable changes in both stomach sensation and gastric-evoked brain activity. These changes were significantly associated, in a dose-dependent fashion. We propose that this approach provides an opportunity to better understand the role of gut-related symptoms in human pathological conditions and might yield fundamental insights into how gut feelings are communicated to the human brain.Competing Interest StatementThe authors have declared no competing interest.(CPM)Cycles per minute,(EEG)Electroencephalogram,(EGG)Electrogastrogram,(ERP)Evoked response potential,(FP)False positive,(HR)Hit rate,(LPP)Late positive potential,(M)Mean,(μV)Microvolts,(STAI)Spielberger State Trait Anxiety Inventory,(STD)Standard deviation ER -