The Vagus Nerve. Stimulating the pathway connecting body and brain can change patients’ lives – Zoe Fisher and Andrew H Kemp.

Practicing mindfulness meditation improves the functional connectivity of the default mode network which lowers a biomarker for inflammation (Interleukin-6) while improving executive control and stress resilience.

Health and wellbeing is something of a buzz phrase these days. It’s become almost an ideal state: if one takes care of their health and wellbeing, then they will be “healthy”.

But what exactly is health and wellbeing?

The World Health Organization defines health as complete physical, mental and social wellbeing. “Wellbeing” is defined in dictionaries as anything from the physical state of being comfortable, to health and happiness. However, these definitions suggest that patients with chronic diseases or lifelong injuries cannot be healthy and/or happy.

By contrast, some have argued that people with cancer might be considered healthy if they have the following attributes: optimism, sense of control, purpose and meaning, positive social ties, and a nurturing family.

We also think that wellbeing in patients with chronic conditions can be improved, it just takes a different approach. At Swansea University’s award winning health and wellbeing academy we have been providing a unique service for brain injury patients, happiness groups.

Despite the name, this strategy is not just limited to making people “happy” again. Over eight weeks, the participants cover a variety of topics, such as positive health, positive emotions, and building meaning and purpose in life. We help them identify and focus on their strengths rather than their weaknesses, and to develop positive social relationships with other group members. In addition, we encourage patients to take part in different activities, such as technology projects and other outdoor skill building programmes, through which clinicians weave neurorehabilitation and psychological therapies.

Our aim is to treat both physical health conditions and improve mental wellbeing by stimulating the pathway that connects both body and mind: The Vagus Nerve.

What patients need

Brain injury is a condition that leads to a change in one’s identity for which little help is available. Patients usually have psychological treatments such as cognitive behavioural therapy as well as education and reassurance. While doctors typically focus on reducing impairment, we have found that this is not what what patients say they need. They want opportunities to use their strengths, to contribute and feel valued.

As researchers, we are especially interested in the functioning of the Vagus nerve and its role in social interactions and longevity. The vagus nerve is associated with our capacity to regulate emotion, to engage and connect with others, and may even predict whether or not we survive the next decade.

Studies have shown that the increases in positive emotion which come from meditation, for example, are dependent on baseline vagal function. However, this research also shows that increases in positive emotion can lead to increased perceptions of social connectedness, which drive further increases in vagal function in an upward spiral relationship.

These findings are especially interesting when one considers other evidence that demonstrates positive social connections have greater effects on longevity than physical activity. And that they have a roughly equivalent effect to stopping smoking 15 cigarettes a day.

Friendship is now considered to be a critical factor impacting on health and wellbeing. Loneliness, meanwhile, significantly increases the risk of premature death. It is entirely possible that the vagus nerve mediates these outcomes, which is why we are taking such a different approach with our groups.

A new approach

To further explain what we are doing, we have recently developed a “GENIAL” model, which highlights the effects that connecting with others has on vagal nerve function and what augmenting vagal function might do to our social relationships and health and wellbeing.

In English, the word “genial” means “friendly”, so this acronym helps to emphasise the important role of positive social relationships in health. We also use GENIAL as an acronym to refer to the fact that there is more than one way to achieve health and wellbeing. For example, it encompasses the ways that different genes interact with environmental stimuli, which in turn influences the vagal nerve function that underpins social interactions, and the downstream physiological cascade leading to longevity or premature mortality.

The model also helps to facilitate our group activities. Participants learn, for instance, that vagal function can be enhanced through a variety of positive health behaviours such as physical activity, diet, as well as techniques used in positive psychology such as meditation.

Over the last decade, there has been much new knowledge generated by researchers on how to improve health and wellbeing. But while public health advocates remain focused on behaviours such as exercise, diet and alcohol consumption, the miss other opportunities.

Our model and group strategy, on the other hand, take a different approach. They were inspired by patient feedback and scientific evidence including developments in positive psychology. But this is not just about personal health and wellbeing. Ideas like ours have the potential to revolutionise the health service and communities, too.

The vagus nerve wanders everywhere between your brain and gut as part of a feedback loop and the “gutbrain axis.”

Mindfulness Meditation and the Vagus Nerve Share Many Powers

Christopher Bergland

Mindfulness and vagus nerve stimulation can optimize the default mode network.

This morning, I noticed an exciting correlation between two new studies which separately identified that optimizing the functional brain connectivity of the default mode network (DMN) can have significant psychological and physical health benefits.

The first study found that stimulating the vagus nerve dramatically reduces the severity of depression.

The second study found that mindfulness meditation also optimized functional connectivity of the default mode network which lowered inflammation and improved the brain’s ability to manage stress and anxiety.

After reading dozens of new scientific studies over coffee this morning, I had an ‘aha’ moment when I realized that these two studies, both published in the current issue of Biological Psychiatry, are using similar language to describe very different research.

Both of these studies offer holistic ways to optimize the functional connectivity of the default mode network using non pharmacological interventions that have the power to improve psychological and physical wellbeing.

Non-Invasive Vagus Nerve Stimulation Can Significantly Reduce Depression

The first study used a new noninvasive vagus nerve stimulator (tVNS) to improve functional connectivity of the default mode network which reduced symptoms of major depressive disorder (MDD).

The February 2016 study, “Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder,” was published in Biological Psychiatry This research was a collaboration between the China Academy of Chinese Medical Sciences and Harvard Medical School.

Patients with major depressive disorder who volunteered to participate in this study either received the new transcutaneous VNS or a ‘sham’ VNS, which served as a placebo. Then, they underwent a functional neuroimaging (fMRl) scan both before and after one month of treatment. When the researchers compared patients who received real or sham VNS, they found that the patients who received real VNS showed significant improvement of their depressive symptoms.

The real breakthrough of this new vagus nerve stimulator is that it’s inexpensive and completely non-invasive. The device sits in the ear like a pair of headphones. Traditional VNS is a neurostimulation technique that has been used to alleviate treatment resistant symptoms of depression. Typically, VNS is costly and requires potentially risky neurosurgery to implant the device.

In a press release, lead author Peijing Rong concluded, “This non-invasive, safe and low cost method of depression treatment can significantly reduce the severity of depression in patients and shows promise for future use.”

Mindfulness Meditation Alters Default Mode Network Brain Connectivity

The second study identified that practicing mindfulness meditation improves the functional connectivity of the default mode network which lowers a biomarker for inflammation (Interleukin-6) while improving executive control and stress resilience.

The Carnegie Mellon University (CMU), researchers identified how mindfulness meditation optimizes brain connectivity and lowers stress. The fMRl brain scans from this study showed that mindfulness meditation training increased the functional connectivity of the participants’ resting default mode network in areas directly linked to attention and executive control.

The February 2016 study, “Alterations in Resting State Functional Connectivity Link Mindfulness Meditation with Reduced Interleukin-6: A Randomized Controlled Trial,” was published in Biological Psychiatry.

For this randomized controlled trial, 35 jobseeking adults, who were experiencing the stress of unemployment, were enrolled in an intensive three day mindfulness meditation retreat program or a well matched relaxation retreat program that did not have a mindfulness component.

The participants who completed the mindfulness meditation program showed changes in brain functional connectivity and reduced Interleukin-6 which accounted for the lower inflammation levels. Participants who relaxed, but didn’t practice mindfulness meditation, did not show similar outcomes.

In a press release, David Creswell, lead author and associate professor of author and associate professor of psychology in the Dietrich College of Humanities and Social Sciences at CMU, said,

“We’ve now seen that mindfulness meditation training can reduce inflammatory biomarkers in several initial studies, and this new work sheds light into what mindfulness training is doing to the brain to produce these inflammatory health benefits.

We think that these brain changes provide a neurobiological marker for improved executive control and stress resilience, such that mindfulness meditation training improves your brain’s ability to help you manage stress, and these changes improve a broad range of stress related health outcomes, such as your inflammatory health.

Conclusion: Mindfulness Meditation and Vagus Nerve Stimulation As a Dynamic Duo

The most exciting aspect of these studies is the prospect of combining mindfulness meditation with the new non-invasive vagus nerve stimulator to create a double whammy that leads to a wide range of psychological and physical health of psychological and physical health benefits.

Currently, I listen to a playlist from iTunes when practicing my daily mindfulness meditation. I can easily see plugging in the new VNS headphone like device while meditating to reap all the benefits of both mindfulness meditation and vagus nerve stimulation simultaneously.

Both of these studies offer inexpensive and effective ways to improve people’s health without the use of pharmaceuticals or invasive surgeries. Stay tuned for more on the fascinating interconnections between the vagus nerve, mindfulness meditation, and the default mode network.


The Default Mode Network

The default mode network (sometimes called simply the default network) refers to an interconnected group of brain structures that are hypothesized to be part of a functional system. The default network is a relatively recent concept, and because of this there is not yet a complete consensus on which brain regions should be included in a definition of it.

Regardless, some structures that are generally included are the medial prefrontal cortex, posterior cingulate cortex, and the inferior parietal lobule. A few of the other structures that may be considered part of the network are the lateral temporal cortex, hippocampal formation, and the precuneus.

What is the default mode network and what does it do?

The concept of a default mode network was developed after researchers inadvertently noticed surprising levels of brain activity in experimental participants who were supposed to be “at rest”, in other words they were not engaged in a specific mental task, but just resting quietly (often with their eyes closed). Although the idea that the brain is constantly active (even when we aren’t engaged in a distinct mental activity) was clearly expressed by Hans Berger in the 1930s, it wasn’t until the 1970s that brain researcher David Ingvar began to accumulate data showing that cerebral blood flow (a general measurement of brain activity) during resting states varied according to specific patterns; for example, he observed high levels of activity in the frontal lobes of participants at rest.

As neuroimaging methods became more accurate, data continued to accumulate that suggested activity during resting states followed a certain order; this data was easy to come by because in many neuroimaging studies, asking participants to rest in a quiet state is considered the control condition. In the early 2000s, Raichle, Gusnard, and colleagues published a series of articles that attempted to more specifically define the areas of the brain that were most active during these rest states. It was in one of these publications that they used the term default mode to refer to this resting activity, phraseology which led to the brain areas that exhibited default mode activity being considered part of the default mode network.

Thus, the default mode network is a group of brain regions that seem to show lower levels of activity when we are engaged in a particular task like paying attention, but higher levels of activity when we are awake and not involved in any specific mental exercise. It is during these times that we might be daydreaming, recalling memories, envisioning the future, monitoring the environment, thinking about the intentions of others, and so on, all things that we often do when we find ourselves just “thinking” without any explicit goal of thinking in mind.

Additionally, recent research has begun to detect links between activity in the default mode network and mental disorders like depression, anxiety, and schizophrenia. Furthermore, therapies like meditation have received attention for influencing activity in the default mode network, suggesting this may be part of their mechanism for improving well-being.

The concept of a default mode network is not without controversy. There are some who argue that it is difficult to define resting wakefulness as constituting a unique state of activity, as energy consumption during this state is similar to energy consumption during other waking states. Others have asserted that it is unclear what the patterns of activity during these resting states mean, and thus what the functional importance of the connections between the regions in the default mode network really are.

These caveats are worth keeping in mind when you come across research on the default mode network, as, especially due to its relationship with meditation, it is becoming a frequently used term in popular neuroscience descriptions of brain activity. The idea of a default mode network, however, is not universally accepted; even those who endorse the idea concede there still is a lot of work left to do to figure out the network’s exact functions.

Regardless, at the very least the concept of a default mode network has sparked interest in understanding what the brain is doing when it is not involved in a specific task, and this line of research may help us to gain a more comprehensive understanding of brain function.

Buckner RL, Andrews-Hanna JR, & Schacter DL (2008). The brain’s default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1-38 PMID: 184009


Vagus Nerve Stimulation Helps Treatment Resistant Depression

Christopher Bergland

Treatment resistant depression responds to vagus nerve stimulation (VNS), study finds.

A landmark study has found that adjunctive vagus nerve stimulation (VNS) significantly improves treatment resistant depression outcomes over a 5-year period. These findings were published July1 in the American Journal of Psychiatry.

This study provides empirical evidence that VNS, which delivers mild electrical impulses to the vagus nerve via an implanted device, has robust antidepressant benefits when compared to a “treatment-as-usual” approach of medication, psychotherapy, and/or electroconvulsive therapy. Treatment resistant patients receiving adjunctive VNS experienced higher rates of depression remission and symptom improvement when compared to patients only receiving traditional care.

Why Does Vagus Nerve Stimulation Help Treatment Resistant Depression?

Vagus means “wandering” in Latin. The vagus nerve is known as the “wandering nerve” because it has multiple branches that diverge from the brainstem and wander to the lowest viscera of your intestines touching your heart and most major organs along the way.

As part of a gut-brain axis, the vagus nerve maintains a bi-directional feedback loop between your state of mind and what Claude Bernard would call your milieu intérieur (the environment within).

Your vagus nerve acts as a central command center for your parasympathetic nervous system (PNS) which regulates “restand-digest” or “tend-and-befriend” psychophysiological responses marked by positive emotions and feeling safe and sound. On the flip side, to maintain homeostasis, the sympathetic nervous system (SNS) drives the “fight-or-flight” mechanism and fuels stress responses marked by adrenaline and cortisol production in response to fear-based negative emotions, actual danger, catastrophizing, or a sense of uncertainty.

Based on today’s current events, it’s worth noting that the uptick of free-floating anxiety spawned by domestic political shenanigans and global uncertainty (triggered by such things as North Korea’s intercontinental ballistic missile testing) can easily cause your fight-or-flight response to become hyperactive and run wild. Even if you don’t suffer from clinical depression, making an effort to keep your vagus nerve engaged using holistic “vagal maneuvers” such as diaphragmatic breathing and tonic levels of daily physical activity, is more important than ever. (To read more on this topic, check out my nine-part Psychology Today series “A Vagus Nerve Survival Guide to Combat Fight-or-Flight Urges”).

In 1921, a Nobel Prize winning German physiologist, Otto A Loewi, made a happenstance discovery in his laboratory that would ultimately lead to the revelation that whenever someone takes a deep breath and exhales slowly his or her vagus nerve squirts out a powerful “Xanax-like” substance that immediately slows heart rate and inhibits fight-or-flight nervous system responses. (This is why slow abdominal breathing makes you feel calm.)

At the time, Loewi coined this vagus-produced tranquilizer vagusstuff (German for “vagus substance”). Vagusstuff proved to be the first neurotransmitter ever discovered and is called “acetylcholine” today. In the early 21st century, acetylcholine was identified as a key building block for a complex anti-inflammatory reflex that is enhanced by vagus nerve stimulation.

Higher vagal tone (VT) is linked to less inflammation, lower anxiety, better emotion behaviors. Conversely, lower vagal tone is associated with systemic inflammation, anxiety disorders, clinical depression, and a wide range of other maladies. Therefore, it makes sense that stimulating the vagus nerve has the power to create an upward spiral of psychological and physical wellbeing.

In 1997, Mark George, of the Medical University of South Carolina (MUSC) in Charleston, was one of the first doctors to implant a VNS device for the treatment of depression. Since then, he’s observed the long-term positive effects of VNS informally by staying in touch with dozens of patients. For example, he recently told Psychiatric News, “The patients by and large seem much more social and active than before. When you get questions such as, ‘Is it okay if I scuba dive with my VNS implant?’ it suggests the patient is doing well.”

In 2006, the US. Food and Drug Administration (FDA) approved VNS for the treatment of depression, but requested there be an ongoing surveillance study. This led to the creation of the “Treatment Resistant Depression Registry” which has continuously tracked the outcomes of patients using vagus nerve stimulation receiving traditional care for their depression.

As part of this registry, the recent 5-year study on the benefits of VNS was conducted across 61 different sites in the United States and included a total of 795 patients who were experiencing a major depressive episode (unipolar or bipolar depression) that had lasted continuously for at least two years; or patients who experienced three or more major depressive episodes (including the current episode) and hadn’t responded to four or more depression treatments (including electroconvulsive therapy).

Of the 705 study participants, 494 received a VNS implant in addition to their usual treatments, while 301 continued with treatment as usual-which included psychopharmaceuticals, psychotherapy, and/or ECT. In their latest paper, the authors describe the results of their ongoing study:

“The adjunctive VNS group had better clinical outcomes than the treatment as usual group, including a significantly higher 5-year cumulative response rate (67.6 percent compared with 40.9 percent) and a significantly higher remission rate (cumulative first-time remitters, 43.3 percent compared with 25.7 percent).”

Although this 5-year study identifies a correlation between VNS and significantly better treatment outcomes, the researchers are still unsure of causation.

The million-dollar question remains, “Why does vagus nerve stimulation help depression?”

One hypothesis is that clinical depression may be linked to chronic activation of the “fight-or-flight” mechanisms of the sympathetic nervous system which perpetuates a complex chain reaction fueled by systemic inflammation and makes it difficult for brain cells to repair and recover consistently. Although much more research is needed before drawing any conclusions about the correlation between systemic inflammation and clinical depression, it is worth noting that vagus nerve stimulation dramatically reduces inflammation.

In July 2016, an international team of researchers reported in the Proceedings of the National Academy of Sciences that vagus nerve stimulation reduced systemic inflammation and improved outcomes for patients with rheumatoid arthritis by inhibiting cytokine production. The neuroscientists and immunology experts involved in this study mapped the neural circuitry that regulates inflammation and found that action potentials transmitted in the vagus inhibited the production of pro inflammatory cytokines.

The researchers believe that VNS could provide a potent and highly effective drug free alternative for treating debilitating inflammation. Co-author of this study, Kevin J. Tracey, is president and CEO of the Feinstein Institute for Medical Research. He also discovered and coined the term “The Inflammatory Reflex.” In a statement, Tracey said:

“This is a real breakthrough in our ability to help people suffering from inflammatory diseases. While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself.”

The growing body of research on using vagus nerve stimulation to help those with treatment resistant depression and to downregulate the molecular expression of inflammatory cytokines offers tremendous promise. That said, more research and randomized, blinded, controlled clinical trials are needed before the general population should consider using various types of VNS implants as a routine part of depression management.

But there is good news: The results of ongoing studies that will provide more finely tuned best practices and other methods of VNS are on the horizon.

Stay tuned!

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