Obesity: a centimeter-sized device provides the feeling of fullness by stimulating the endings of the vagus nerve with light


Gastric bypass surgery is sometimes the last resort for those who struggle with obesity or have serious health-related issues due to their weight.

Since this procedure involves making a small stomach pouch and rerouting the digestive tract, it is very invasive and prolongs the recovery period for patients.

In a new study, researchers at Texas A&M University have described a medical device that might help with weight loss and requires a simpler operative procedure for implantation.

Researchers said their centimeter-sized device provides the feeling of fullness by stimulating the endings of the vagus nerve with light. Unlike other devices that require a power cord, their device is wireless and can be controlled externally from a remote radio frequency source.

“We wanted to create a device that not only requires minimal surgery for implantation but also allows us to stimulate specific nerve endings in the stomach,” said Dr. Sung II Park, assistant professor in the Department of Electrical and Computer Engineering.

“Our device has the potential to do both of these things in the harsh gastric conditions, which, in the future, can be hugely beneficial to people needing dramatic weight-loss surgeries.”

Further details about their device are published in the January issue of Nature Communications.

Obesity is a global epidemic. Furthermore, its associated health problems have a significant economic impact on the U.S. health care system, costing $147 billion a year.

Additionally, obesity puts people at risk for chronic diseases such as diabetes, heart disease and even some cancers. For those with a body mass index greater than 35 or who have at least two obesity-related conditions, surgery offers a path for patients to not only lose the excess weight but maintain their weight over the long term.

In recent years, the vagus nerve has received much attention as a target for treating obesity since it provides sensory information about fullness from the stomach lining to the brain.

Although there are medical devices that can stimulate the vagus nerve endings and consequently help in curbing hunger, these devices are similar in design to a pacemaker, that is, wires connected to a current source provide electrical jolts to activate the tips of the nerve.

Tiny wireless device sheds light on combating obesity
Dr. Sung II Park’s paddle-shaped device consists of a harvestor that contains microchips for wireless communication. The harvestor also produces currents to power LEDs inserted near the end of the shaft. Credit: Texas A&M University College of Engineering

However, Park said wireless technology, as well as the application of advanced genetic and optical tools, have the potential to make nerve stimulation devices less cumbersome and more comfortable for the patient.

“Despite the clinical benefit of having a wireless system, no device, as of yet, has the capability to do chronic and durable cell-type specific manipulation of neuron activity inside of any other organ other than the brain,” he said.

To address this gap, Park and his team first used genetic tools to express genes that respond to light into specific vagus nerve endings in vivo. Then, they designed a tiny, paddle-shaped device and inserted micro LEDs near the tip of its flexible shaft, which was fastened to the stomach.

In the head of the device, called the harvester, they housed microchips needed for the device to wirelessly communicate with an external radio frequency source. The harvester was also equipped to produce tiny currents to power the LEDs. When the radio frequency source was switched on, the researchers showed that the light from the LEDs was effective at suppressing hunger.

The researchers said they were surprised to uncover that the biological machinery coordinating hunger suppression in their experiments was different from conventional wisdom.

In other words, it is widely accepted that when the stomach is full, it expands and the information about stretch is conveyed to the brain by mechanoreceptors on the vagus nerve.

“Our findings suggest that stimulating the non-stretch receptors, the ones that respond to chemicals in the food, could also give the feeling of satiety even when the stomach was not distended,” said Park.

Looking ahead, he said that the current device could also be used to manipulate nerve endings throughout the gastrointestinal tract and other organs, like the intestine, with little or no modifications.

“Wireless optogenetics and identifying peripheral neural pathways that control appetite and other behaviors are all of great interest to researchers in both the applied and basic fields of study in electronics, material science and neuroscience,” said Park.

“Our novel tool now enables interrogation of neuronal function in the peripheral nervous systems in a way that was impossible with existing approaches.”

In life, pursuing rewards often comes at a cost which is epitomized in the idiom that there is no free lunch. Imagine the cafeteria at work serves decent food, but there is also a stellar restaurant offering your favorite dish as an affordable lunch special. Although the prospective benefits are different, we may go for the cafeteria instead of the restaurant because it is close by.

In such cases, we are confronted with the challenge to integrate the costs of action such as the effort of walking a distance with its anticipated benefits, such as eating a better meal. According to economic theories, an optimal decision-maker discounts prospective benefits by the costs of actions incurred1.

Alternatively, idioms in German and English suggest a second route: you may go with your gut in deciding which option to pick and how much effort to put in2. To date, these two decision-making strategies have often been portrayed as (more or less) independent processes and, specifically, the role of the gut has been commonly dismissed as primarily figurative2.

However, there is emerging evidence from preclinical studies pointing to a vital role of gut-derived signals in the regulation of motivation via dopaminergic circuits3,4. Although these results challenge the assumption that the gut plays only a figurative role in human motivation, a conclusive experimental demonstration of such a modulation in humans is lacking to date.

To ensure body homeostasis, it is pivotal to regulate motivation and energy metabolism in concert. This process is called allostasis5. As an important part of the autonomic nervous system, the vagus nerve is involved in allostatic regulation through its afferent and efferent pathways6.

To control food intake, vagal afferents primarily provide negative feedback signals7, routed via the nucleus tractus solitarii (NTS). These vagal afferent projections are sufficient as decerebrated rats still terminate meal intake8. In line with this idea, chronic vagus nerve stimulation (VNS) has been consistently shown to reduce body weight in animals and humans.

Preclinical studies indicate that this is primarily due to reduced food intake7,9. Likewise, two recent studies have shown that acute taVNS reduces gastric myoelectric frequency of the stomach10. At the same time, acute VNS has reinforcing properties leading to sustained self-stimulation and conditioning preferences for flavors or places via a dopaminergic mechanism3,11.

Furthermore, activation of vagal afferents regulates learning and memory in rats and humans suggesting a role in reward seeking12,13. Therefore, chronic reductions in food intake could be linked to acute increases in motivational drive by a combination of afferent and efferent effects.

Within the feeding circuit, the NTS serves as a hub relaying metabolic information to the midbrain and forebrain8,14 including to dopaminergic neurons in the substantia nigra3. Vagal afferent activation can thereby indirectly modulate key brain circuits involved in reward15 and energy homeostasis8, because the presence of nutrients in the gut evokes dopamine release in the dorsal striatum tracking caloric load4,16.

Notably, the dorsal striatum is known to play a critical role in the allocation of response vigor17,18, and the invigoration (or energization) of behavior via dopamine signaling19,20, pointing to a link between energy metabolism and goal-directed action.

In addition, noradrenergic signaling has also been shown to facilitate invigoration in monkeys21. Such an invigorating mechanism may help to explain why VNS has elicited antidepressive effects, even in patients who were treated for epilepsy and did not show improvement of epileptic symptoms6.

Taken together, the vagal afferent projections to the NTS are a promising candidate for modulatory input onto brain circuits encoding motivation.

Despite the growing evidence for vagal regulation of goal-directed behavior, it is still unclear whether preclinical findings using predominantly food as reward and invasive stimulation will extend to humans and secondary reinforcers such as money. Moreover, it is not known whether there is a lateralization of vagal afferent signals in humans, as observed in rodents3.

Until recently, research on vagal input in humans was limited due to the invasive nature of implanted VNS devices. Today, non-invasive transcutaneous auricular VNS (taVNS) has become a promising avenue for research and, potentially, treatment of various disorders.

Commonly, taVNS is applied via the ear targeting the auricular branch of the vagus nerve, where the stimulation elicits far-field potentials22. Successful activation of the NTS has been demonstrated in animals after taVNS23. Likewise, human neuroimaging studies using fMRI have shown enhanced activity in the NTS and other brain regions related to motivation including the dopaminergic midbrain and striatum after concurrent taVNS24–26.

Compared to implanted VNS, similar therapeutic effects have been reported after taVNS27–29. In line with the hypothesized potential of VNS to alter motivational processes, we recently found that taVNS affects value-based learning in a go/no-go reinforcement learning task13. Thus, non-invasive taVNS may provide an effective means to study the endogenous regulation of motivation according to homeostatic needs.

Taken together, the vagus nerve may provide an important interface connecting metabolic signals from the periphery with central nervous circuits involved in goal-directed, allostatic behavior. Here, we tested whether non-invasive taVNS—applied to emulate interoceptive feedback signals—would modulate effort if different rewards are at stake (food or money).

To better understand potential changes in motivation, we focus on the motivational phases of invigoration versus effort maintenance. In our task, invigoration relates to how quickly a participant energizes effortful behavior, whereas maintenance relates to how durably effort is kept up18.

Due to the modulatory effects of taVNS on the brain and on behavior, we hypothesized that taVNS would enhance the invigoration of effort by altering the perceived benefit of effortful behavior, which has been linked to dopamine tone before30,31. Similarly, taVNS-induced increases in noradrenaline would also lead to an enhanced invigoration of effort21.

We also assess whether taVNS alters effort maintenance by reducing the costs of actions, which may point to a serotonergic mechanism instead32,33. Moreover, we test whether taVNS applied to the right versus the left ear would generalize beyond the regulation of food reward as suggested by Han et al.3.

We find that taVNS increases invigoration, but not maintenance of effort or rated wanting, and that the side of the stimulation affects generalization beyond food reward.

reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366927/

More information: Woo Seok Kim et al, Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways, Nature Communications (2021). DOI: 10.1038/s41467-020-20421-8


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