Non-invasive assessment and modulation of brain-gut interoception in humans

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PROJECT SUMMARY/ABSTRACT Interoception refers to the representation of the internal states of an organism, and includes the processes by which it senses, interprets, integrates, and regulates signals from within itself. Interoception is increasingly viewed as a bidirectional process between the brain and body, in which multiple feedback and feedforward loops lead to an internal representation of the body. The vagus nerve is intimately involved in autonomic control of the upper gastrointestinal (GI) tract, with afferent projections to medullary brainstem nuclei. In turn, interoceptive pathways can also be directly targeted for clinically beneficial neuromodulation and non-invasive neuromodulatory techniques that interact with brainstem vagal circuitry, including transcutaneous auricular vagal nerve stimulation (taVNS), have been reported to modulate efferent visceral vagal pathways via the engagement of nucleus tractus solitarii (NTS). However, broader understanding of taVNS effects on gastric function and brain response to gastric interoceptive signaling is needed, and requires tools to directly probe the gut-brain axis in humans. In our study, we will combine a fully non-invasive experimental framework including sequential gastric and brain Magnetic Resonance Imaging (MRI) with calibrated meal ingestion and MRI- compatible taVNS to evaluate the modulation of visceral interoception along the brain-gut axis. Aim 1 will evaluate gastric function and brain response to gastric interoceptive signaling following calibrated meal ingestion. In Aim 2, we will then investigate taVNS modulation of gastric function and brain response to gastric interoceptive signaling. The proposed study will contribute new insights into the bidirectional gut-brain interaction underlying gastric interoception, and its modulation via non-invasive neuromodulatory techniques that specifically target interoceptive pathways (i.e. taVNS).