# Developing a novel stimulus paradigm and interface of vagal nerve stimulation (VNS) to treat obesity

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Rationale: By 2018, 31 states had an obesity rate ≥30% and none <20%. Costs due to obesity are estimated
at $190B/yr. 72% of Veterans are overweight (45%) or obese (27%), of which 66% have hypertension and
31% have diabetes. Researchers use vagal nerve stimulation (VNS) to treat a number of conditions, including
obesity. Sensory afferents in the vagus nerves innervate the stomach and relay information about the state of
the stomach, particularly the degree of stomach wall stretch associated with increased stomach volume.
However, VNS parameters vary widely and it is unknown how changes in stimulus parameters alter outcomes.
Until the parameter-to-outcome relationship is mapped, developing optimal stimulus waveforms is impossible.
Objective: The objectives of this study are to map the relationship between stimulus parameters and 1) nerve
recruitment, 2) brain activity in regions associated with satiety, and 3) food consumption. Further, a novel
stimulus waveform and interface for delivering more effective bilateral VNS will be evaluated. Numerous
hypotheses will be tested through a series of animal experiments over a period of 4 years.
Research Plan and Methodology: During Aim 1, the subdiaphragmatic vagus nerve will be implanted with a
nerve cuff electrode in rats. The rats will remain healthy or become obese depending on their diet. Once per
month, the animal will receive subdiaphragmatic VNS (sVNS) while an fMRI image of brain activity is acquired.
The effects of VNS intensity, VNS waveform, diet type, and time on activation of the brain in key regions
responsible for satiety and reward will be determined. During Aim 2, the subdiaphragmatic vagus nerve will be
implanted with a nerve cuff electrode in rats. The rats will have simultaneous access to three diet types. Each
week VNS will be provided for multiple days. The amount and type of food consumed as well as the overall
activity of the rat during days of stimulation will be compared to days without stimulation. The effects of VNS
intensity and waveform on food consumption and activity will be determined. During Aim 3, a novel cuff that
wraps around the esophagus and delivers bilateral VNS will be implanted. As with Aim 2, the rats will have
simultaneous access to three diet types and both food consumption and activity during days of stimulation will
be compared to days without stimulation. The effects of VNS intensity on food consumption and activity will be
determined and compared to those found in Aim 2. Esophageal resistance to distension and histology will be
used to assess if the implant remains safe after 6 months. Additionally, the map between VNS stimulus
intensity and axon recruitment within the vagus nerve will be mapped.
Expected Outcomes: This study provides the necessary data to facilitate understanding how sVNS effects the
system at three levels by generating a map that links sVNS parameters to: 1) axon recruitment within
the vagus nerves; 2) brain activation; and 3) short-term...

## Key facts

- **NIH application ID:** 10425537
- **Project number:** 1I01RX003967-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** MATTHEW Anthony SCHIEFER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425537

## Citation

> US National Institutes of Health, RePORTER application 10425537, Developing a novel stimulus paradigm and interface of vagal nerve stimulation (VNS) to treat obesity (1I01RX003967-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425537. Licensed CC0.

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