# Design and Application of Custom Waveforms to Restore and Control Satiety

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Rationale: By 2014, 22 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, the two most common comorbidities associated with obesity. Researchers use vagal
nerve stimulation (VNS) to treat a number of conditions, including obesity. The vagal nerve is the
parasympathetic branch of stomach innervation whereas the lesser-studied splanchnic nerve provides
sympathetic innervation. Splanchnic nerve stimulation (SpNS) has also been used to treat obesity. Sensory
afferents in these nerves relay information about the state of the stomach. How and why VNS and SpNS work
remain unknown. Stimulus parameters vary widely and are often accompanied by side-effects. The limited
success and undesired side effects are hypothesized to be due to the stimulus waveform. This grant seeks to
understand the neural population code associated with stomach distension. It also assesses the effect of novel
VNS and SpNS waveforms designed to mimic the neural population code and reduce side-effects on body
weight in obese rats.
Objective: The objectives of this study are to 1) elucidate the neural mechanisms underlying obesity and 2)
develop and assess the effects of novel stimuli on eating behavior in obese rats. Numerous hypotheses will be
tested through a series of animal experiments over a 4 year time period.
Research Plan and Methodology: During Aim 1, in a series of non-survival experiments, the vagal and
splanchnic nerves will be implanted with electrodes in rats. The rats will be healthy or made overweight or
obese using a moderate or high-fat diet. The animal’s stomach will be distended with an intragastric balloon to
mimic food consumption. Intragastric pressure will be recorded. Nerve recordings will provide insight to the
neural response in the two nerves to stomach filling. The effect of diet and body mass index (BMI) on
discharge pattern will be assessed. During Aim 2, in a series of survival experiments, nerve cuff electrodes will
be implanted around the vagal and splanchnic nerves of rats. The rats will be either a healthy weight or obese.
After healing, the rats will receive VNS, SpNS, or both using either standard time-invariant or novel time-variant
waveforms. A time-variant waveform will be developed from recorded neural patterns and histology obtained in
Aim 1 using 3D finite element models. Effects of stimulus location and waveform type on weight and activity
will be determined over a 20-week period. Histology will be conducted to assess the effects of stimulus on
nerve health.
Immediate and Long-Term Career Goals: The immediate career goal is to become immersed within the field
of obesity research and expand scientific understanding of how electrical stimulation applied to autonomic
nerves can be used to reduce body weight. The long-term career goal is to become an independent clinical
researcher with a lab at...

## Key facts

- **NIH application ID:** 10390275
- **Project number:** 5IK2RX001817-05
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** MATTHEW Anthony SCHIEFER
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390275

## Citation

> US National Institutes of Health, RePORTER application 10390275, Design and Application of Custom Waveforms to Restore and Control Satiety (5IK2RX001817-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10390275. Licensed CC0.

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