Michael VanElzakker Phd, is a neuroscientist affiliated at Massachusetts General Hospital, Harvard Medical School, and Tufts University. He has two primary research interests: PostTraumatic Stress Disorder, or PTSD, and Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). He recently published a paper describing a novel hypothesis for ME/CFS that centers on infection of the Vagus Nerve.
Note: This interview was transcribed from written notes and not an audio recording.
Hypothesis: a proposed explanation made on the basis of limited evidence as a starting point for further investigation.
The UK PACE Trial on ME/CFS: A highly criticized trial on ME/CFS. The Trial’s results don’t fit with what most ME/CFS patients experience in real life. Please read journalist David Tuller’s detailed critique of the trial.
Unrest: A 2017 Documentary about ME/CFS. Summary: “Jennifer Brea is about to marry the love of her life when she’s struck down by a fever that leaves her bedridden. When doctors tell her “it’s all in her head,” she turns her camera on herself and her community as she looks for answers and fights for a cure.”
Me: Hi Mike, thanks for taking the time to talk! How are you?
Mike: No problem. I’m good, actually working on setting up a second screening of “Unrest” here at the Martinos Center. We’ll show the documentary on a big screen in one of the conference rooms. Have you seen it?
Me: Yes, it’s very good. My story has a lot of parallels with Jen’s. It accurately portrays a lot of what I’ve dealt with for over 12 years. It’s very painful for me to watch. How do you feel about it?
Mike: It’s great. I’m glad they showed the story of Karina Hanson being taken away from her parents – that’s something only the ME/CFS community knew about for many years. It was sort of surreal to see the story presented on a big screen. It really adds to the film.
Me: Definitely. Also Mike, before I forget, can you clarify your different jobs? You work at both Harvard and Tufts?
Mike: The office I’m sitting in now is at the Martinos Center for Biomedical Imaging, which is part of Massachusetts General Hospital. Mass General is the teaching hospital for Harvard Medical School, so I get a semi-automatic Harvard Med affiliation with my position. But I’m almost never on the main Harvard campus.
Me: Cool, and you teach at Tufts?
Mike: Yes, I’m an adjunct instructor. This semester, I’m teaching a class on research methods that’s required for undergrad clinical psychology majors – the idea is that it will help them to better think critically about the scientific literature by being able to understand methods. I also teach “abnormal psychology” to clinical psychology majors. And next semester I’ll teach a seminar that focuses on the intersection of stress and memory.
Me: Interesting. I’m glad you’re teaching research methods so that your students might learn how to not set up a trial like the UK PACE Trial on ME/CFS.
Mike: I know. In these classes, I work in ME/CFS as a subject as often as I can. And I have used the PACE trial as an example in the research methods class. First to show the importance of choosing reliable/realistic study outcomes. Also though, I’ve pointed out how the PACE trial team went on a press tour with claims that went well beyond their data. I feel that the impact of PACE on patients would not have been so negative if the team had stuck to talking about what they actually found (in terms of results). But they decided to tell the popular press that they discovered how to make people with ME/CFS recover. Again, a claim that’s just way beyond their actual data, even setting aside critiques of how they arrived at those data. Also, in the abnormal psych class I talk about how in some cases psychosocial models for disease aren’t as strong as many people assume and that many conditions that were once thought to be psychosomatic are now understood to not be.
Me: Yeah, the metrics they set for “recovery” in the trial are pretty ridiculous.
Mike: Yes, not to mention that they sent out a biasing flyer in the middle of the trial to all participants, a trial based in subjective measures. Quotes from selected patients saying things like “I feel good” or “This is helping me.”
Me: That’s crazy, I didn’t know that. What an incredible form of bias (once subjects read what other subjects say it can influence how they might rate their own experience).
Mike: Yes it sometimes looks like the PACE team so strongly believe their hypothesis that they can’t see perfectly plausible alternate interpretations of their data. And the ME/CFS UK atmosphere seems to be particularly politically charged, more so than here.
Me: The whole thing is very frustrating. I get particularly annoyed because I’ve now found doctors, friends etc. who take my ME/CFS really seriously. So in my own case, I’m not forced to deal with the “psychosomatic” mindset anymore. Which has freed me up to spend more time learning/reading about actual biological dysfunction in ME/CFS. I wish it could be that way for everyone.
Mike: Yes, it’s frustrating for me in that sense too. When joining the ME/CFS research community I had to make a decision: to put my head down and just do science, or to also really make an effort to interact with and advocate for patients. I decided to advocate for patients, and in order to do that I’ve had to spend hours reading about PACE and digging into related critiques (because that’s what patients are dealing with day-to-day). But that’s time I could spend researching the biology. Also the 5 million that went to PACE: I could do a lot of really relevant/important ME/CFS research with that money.
In terms of doctors, ME/CFS patients have to do a lot of work to find a doctor. Few doctors are familiar with the condition. Sometimes I’m asked “Who’s a good ME/CFS doctor in Boston”, and I don’t know someone to recommend. I know well-intentioned physicians, but they haven’t necessarily kept up with the ME/CFS literature. Also, I think doctors find it harder to accept ME/CFS patients because it takes more time per patient to figure out what might be going on. As we know, its certainly not a situation where they can just prescribe an ME/CFS pill. So right now there isn’t much of a place for the condition to “sit” in the medical world – should it be in infections disease? or neurology? – and we’ll likely see ME/CFS shift and change between specialists for a while.
For example, right now I’m collaborating with a pulmonologist to run exercise tests on ME/CFS patients. It’s a collaborative study where we’ll do patient brain scans before and then after exercise testing (with a focus on tracking changes in the autonomic nervous system). But even this great pulmonologist doesn’t exactly specialize in treating ME/CFS patients, specifically.
Also medical textbooks need to be updated to describe ME/CFS more accurately. In my abnormal psychology class I’ve made a point of showing my students how our own textbook poorly describes the illness. The textbook description isn’t terrible, but it could be way better. There’s mention of ME/CFS in the section of the book that gets into somatoform disorder (a mental disorder that manifests as physical symptoms). Somatoform disorders are a real phenomenon, but is probably vastly over-diagnosed. So I’ll tell students, “Somatoform disorders are real but they ought not to be the first place doctors look!…and should not form the default thinking on any disease. Also it’s not OK to resort to assuming someone has a somatoform disorder because the blood tests you’re running don’t show clear results.” The influential psychiatrist Allen Frances, the primary author of the previous DSM (the manual of psychiatric diagnoses), recently stated that somatoform disorder should not be the default diagnosis for unexplained physical symptoms, and I agree.
Returning to the textbook we use in class, I actually met the textbook author at a conference. We got a drink. In a very collegial way I pointed out how the book’s description of ME/CFS could be updated. For example the XMRV controversy that the book mentions is behind us in my opinion. I’m not sure how seriously the textbook author took my feedback but he sounded sincere and said thank you.
You know what has also been frustrating lately? It seems like each new press release about ME/CFS research states, “Our findings put to rest the idea that ME/CFS is a psychosomatic illness” But IMO, research has existed for decades showing ME/CFS is a biological disease. So by mentioning the psychosomatic theory for ME/CFS we are actually giving it credit. I think we should act like it’s not even worth referencing.
Yes. I’ve realized I need to change my own approach. In the past I’ve been using the standard ME/CFS intro sentence when writing about it: Something like “Chronic Fatigue Syndrome is a poorly understood, crazy complicated disorder/mystery that has everyone completely baffled.” But over the last months I’ve realized that description is just untrue. Of course not everyone agrees on what triggers the illness, but in some cases we kinda do. Many patients (if you ask them!) can tell you how their symptoms started (I got Mono, I got sick when traveling in Colombia and never got better, etc.). It’s hardly like we’re dealing with a complete black box of information. Also, there’s “mystery” surrounding almost every human chronic disease. For example in cancer, we don’t understand why cancer cells can’t stop replicating. But we don’t describe cancer as a hopeless mystery. So I’m going to stop using that kind of language. I feel like it intimidates clinicians/researchers and adds to an aura of debate (“is this psychosomatic or not?”) that’s not justified. It also gives clinicians an excuse to throw up their hands up and say, “It’s just too hard to treat patients with ME/CFS.”
Me: That’s great. I hope other research teams follow your lead. Also, considering this climate, what made you willing to research ME/CFS?
Mike: I have a friend with serious ME/CFS. I was a late user of the internet but when I got on Facebook I reconnected with people I hadn’t talked to for years. I messaged a high school friend of mine, “What have you been up to?” It turned out she had been forced to drop out of law school because of ME/CFS. She was sick as hell. And before having to drop out she was so talented that she was set to graduate early. She’s an engaging person and I could feel her frustration about being sick. Also anger at dealing with being told she had the “yuppie flu” and other misconceptions. This is a bright, motivated person and I could see her devastated by the illness.
At the time I was a University of Colorado undergraduate student. My research focused on stress/memory in PTSD (still my second life!). But I had friends doing neuroimmunology research. I would go to those friends’ presentations and talk to them about neuroimmunology. I also found myself brainstorming about my sick friend. I formed the basis of my Vagus Nerve hypothesis for ME/CFS. Then I chatted with Linda Watkins, a professor in the Department of Psychology and Neuroscience. She’s an esteemed researcher who’s done great work on the intersection of the immune system and the nervous system. She even won the Spanish version of the Nobel Prize. I spoke with her and asked, “What would happen if a neurotrophic virus got right into the Vagus Nerve? Could that look like ME/CFS?” She’s not a hyperbolic person but she seemed really stunned and told me, “Oh my God, all it took was for someone to put it together.” That moment has carried me through a lot of frustration and disappointment as I tried to get people to listen to the idea and follow up.
Me: I love how you listen to your friend and to other patients and use their feedback to help inform your research
Mike: Yes, there’s an obnoxious strain of elitism that often impacts ME/CFS patients. It centers on the idea that patients are fooled by their own silly brains. I feel the opposite way. For example, I have great appreciation for my friend with ME/CFS. I constantly ask her very personal questions about her body/symptoms, and she’s totally willing to give me feedback. To act this way your have to be willing to step outside typical institutional roles in which people like me are the real experts. You have to be willing to think, “This patient is more than likely just as smart as I am. I’m going to interact with this person as a thoughtful, critical human who has real insight into their condition.”
Me: Yes! Before we go on, could you explain the ME/CFS hypothesis you’ve published? It centers on infection of the Vagus Nerve…
Mike: Sure. So when an otherwise healthy person gets sick with pretty much anything, many of the symptoms they experience will be similar no matter what specifically is making them sick. For example, people with both Strep and the flu feel extra tired, achey, and have problems with lack of concentration, loss of appetite, reduced sex drive, etc. This is true despite the fact that the flu is a virus and Strep is a bacterial infection. These similar symptoms occur as part of the body’s general “sickness response:” a response driven by the innate immune system (the more ancient branch of the immune system that first recognizes and combats infection).
These “sickness response” symptoms overlap with important primary symptoms of diseases like ME/CFS. This suggests that a sustained and exaggerated, “sickness response” may be a core component of ME/CFS. How might this come to pass? When the innate immune system detects pathogens (microbes causing disease), it generates cytokines (signaling proteins) in an effort to target and draw attention to the infection. These cytokines are created locally at the site of infection (they don’t always make it into the general bloodstream). Still, the brain is able to perceive and respond to this cytokine activation. So how does this work?
Cytokines are relatively large lipophobic polypeptide molecules, so they don’t easily cross the blood/brain barrier. Instead the brain senses changes in cytokine activation via a nerve that conducts signals from the body to the brain, the Vagus Nerve. The Vagus Nerve is an extremely important conduit between the nervous system and the immune system (especially because it densely innervates parts of body in contact with outside world like the lungs and stomach).
A number of key pathogens such as the herpes viruses and the bacterial species Borrelia burgdorferi (Lyme disease) particularly like infecting nerve tissue (they are neurotropic). The hypothesis I put forward in my paper posits that, in ME/CFS, a number of different possible pathogen(s) may directly infect the Vagus Nerve. Resulting cytokine signals relayed to the brain then cause a sharp rise in “sickness response” symptoms. Because the signaling is directly on this sensitive nerve, the brain “overreacts” to these signals and sort of perceives that the entire body (and not just the Vagus Nerve) is infected with pathogens. If this is the case, these “sickness response” symptoms will be exaggerated. In addition, the signaling may not stop correctly, and could induce a snowball effect “feed forward” loop that sustains chronic symptoms. This would be similar to the way a war veteran might still sense pain in an amputated toe (inflammation has triggered a cascade reaction that can sustain itself).
If I were to update the hypothesis today, I would clarify that the Vagus Nerve also plays a large role in relaying information about the human microbiome to the brain, and adapts signaling based on microbiome composition/activity. I would also add rat/mouse studies showing that a pathogen doesn’t have to be fully “active” for nerve and glial tissue to sense its presence. Many viruses persist in latent, chronic forms that aren’t detected well on blood tests but could still be contributing to symptoms.
Me: I love the emphasis on infection of nerve tissue. I’m not sure many people realize how easily nerves can become infected. But question: is it possible that, in ME/CFS the Vagus Nerve is infected, but other chronic pathogens are also infecting other areas of the body (immune cells in the blood, etc.). In that case, the inflammation that triggers “sickness response” by the brain via the Vagus Nerve might not be exaggerated, but actually correct?
Mike: That’s totally possible and something we should also be considering. In order to test that possibility we could look for glial cell activation in the periphery (areas farther away from the central nervous system). Maybe we could add LPS (molecules that trigger a response towards infection) into the periphery and see how Vagus Nerve signaling is impacted. But those are early ideas, and we’d have to sit down more seriously to really tease things apart.
Me: Aren’t most microbes in the body technically “latent” in that microbiome populations are acquired in the womb and often persist with us throughout our lives?
Mike: I was talking more about acquired pathogens. But I agree that the microbiota count as organisms that survive for long periods in the body. And if components of the microbiota begin causing inflammation then the nervous system will likely detect it, relay it to brain, and trigger “sickness behavior” and other related responses.
Me: I see. What factors made you decide to formally publish your hypothesis?
I was a grad student at Tufts working studying PTSD when my advisor went to Korea for a few weeks with her family, so I had a little extra time. I thought, “Why don’t I just write this up?” – I had put a lot of text together from my previous life when I was working in rat labs. But at the time I didn’t intend to get into the ME/CFS field. I thought that if I wrote up my hypothesis, and better explained some info on how cytokines work etc., another research team might take the idea and run with it.
Me: I take it that didn’t happen?
Mike: No. A lesson I learned is that if you want something done you kinda have to do it yourself. Other people might become organically interested in your hypothesis but are unlikely to pursue it as doggedly as someone personally invested. Now I find ME/CFS very interesting to work on, but it’s very different than studying PTSD. In the PTSD research community there exist differences in opinion but most of us are pulling on the same rope. Of course there are controversies, but the atmosphere is not as politically charged as with ME/CFS, where there is broad, controversial argument about what the disease even is. And with ME/CFS I spend a lot of my energy doing patient advocacy work, communicating with patients, etc.
I actually think that part of what I’ve tried to contribute to ME/CFS is being able to talk about this condition while having fancy institutions (Mass General Hospital etc.) listed next to my name, which seems to help ME/CFS legitimacy. It’s a little crazy that thanks to the building I sit in, I can get people to listen to some of the things patients have been screaming for decades.
Me: I think it’s great you were willing to form a solid hypothesis about what causes ME/CFS. When I publish on ME/CFS I also tie my insight to a specific hypothesis. I think doing so makes what I put forward easier to follow, test and even discredit if necessary. But many research teams seem nervous about publishing hypotheses. Why do you think that is and should that mindset change?
Mike: Scientists generally ought to be at least trying to tie their data to a hypothesis. I do wish the field would put more effort into looking at how their data relate to existing hypotheses. Most papers are currently published as phenomenology (aka “this is happening in people’s bodies”), but many lack a framework that attempts to explain why things are happening. That makes it much harder to decide what direction to move in next. In ME/CFS we’ve known for years that metabolism, the immune response, the neurological system are off. It’s time to get more into the specifics of why this might be happening.
Me: Your specific hypothesis aside, I also like the way you wrote your recent ME/CFS paper. You use “simple” language that patients can understand, and went out of your way to define difficult terminology.
Mike: Yes, in the original draft I was writing largely for patients. I actually included way too much background and it got too long, so I dialed it back. But my writing was very much intended for people who didn’t already know the stuff. When I look at the ME/CFS research community almost everyone involved with the disease is personally impacted. So they didn’t set out to formally study ME/CFS from the get-go. This leads to situations where some orthopedic surgeon with a sick cousin decides to research ME/CFS. Such people may need more context for areas outside their training.
That being said, a lot of the simplified language in the paper is a result of the peer-review process. It was the most contentious review process I’ve ever had – some of it was really condescending and smug. The responses had “ou” spellings so I wondered if one of my reviewers was a UK-based psychiatrist. I had to lay stuff out so this reviewer would understand. For example, I created the “terms table” in the paper as a response to the reviewers seeming to not know some of the terms.
I also got a comment from a reviewer commenting on a perceived misuse of an anatomical term stating, “The author seems to have a lack of medical schooling.” And I had to respond, “The reviewer may be unfamiliar with the spinal cord literature” because I was using the term correctly. The reviewer even said they ended up reading an enormous amount of extra literature to follow what I was saying. I appreciate that they did that, but the whole thing took a lot of time.
Also, my original draft didn’t mention the PACE trial. But I got some feedback from a psychiatrist who convinced me to write a section about it. At the time I didn’t really appreciate the depths of the problems in that study, most of which are not visible from only reading the actual publication. I saw it was published in the Lancet (a very highly regarded journal) and assumed it had undergone a rigorous peer review. Now I regret that.
Me: In your paper you mention possible treatment options that fit your hypothesis. How has that been received?
I wanted to be careful talking about treatments because I know that desperate patients sometimes run out and try new things based on very scant evidence. I mentioned antivirals and I have seen some people improve by taking them. But treatment is probably going to require critical thinking and a personalized approach. I don’t think there will ever be an ME/CFS pill – instead we’ll have to think about mechanisms and what’s going on with individual patients. Looking at a patient’s history is important (for example one patient might have had bad chicken pox as a teen, another Mono, another may have gotten sick after traveling). It will probably have to be systems that we target. That can make clinical trials super messy, with some treatments hard to test in a standard randomized placebo controlled trial in which all patients receive the same exact intervention.
We may also need separate treatment interventions (or treatment cocktails): treatments that attempt to get rid of possible infectious agents and others that could help patients manage the putative excess inflammation itself. When it comes to therapies that target the Vagus Nerve, Transcutaneous Vagal Nerve Stimulation is promising. The treatment targets the branch of the Vagus Nerve that comes close to the outer ear and allows action potentials to be sent down the nerve. This stimulates the normal anti-inflammatory reflex of the Vagus. I know a handful of ME/CFS patients who’ve been playing around with this Vagal stimulation. Some have felt better, some have noticed no effect, and others have suffered from side effects. So there’s a spectrum of responses but it’s one arrow in the quiver to think about.
Me: I’m a big fan of how you share information on Twitter. In fact, you recently asked for brain scan donations in a Tweet. I think that’s awesome. It helps people donate money towards a specific goal with an outcome that’s easy to follow
Yes, so far my salary as a post doc has been paid by donors. These donations are sent to Mass General and are enormously helpful. I’m really appreciative. But it’s also so hard to start a research position from scratch. Normally as a post doc I would enter an already-established lab that’s already doing the kind of work I want to do. But I’m starting something totally new with my ME/CFS research. It’s a stupid amount of work:) For that particular project I want to run a handful of brain scans to get good pilot data. Just five scans would be enough, so that’s what I am trying to raise. And even if donations trickle in slowly, when I reach $5900 I can do the scan immediately. That’s opposed to applying a formal grant for millions of dollars and waiting long periods for a decision.
It’s a bit of a Catch-22 because it’s hard to apply for big money without data, and hard to get data without money. If I do the scans with private funding I can use my pilot data to hopefully get a larger government grant. I want to call the NIH’s bluff and see if they really are willing to fund research here. Francis Collins and the NIH seem earnestly invested in helping ME/CFS. So I’m gonna get good pilot data and say, “Here you go!” Now really fund this:)
Me: I’m changing the subject a little, but since you work with PTSD, what do you think about the use of psilocybin as a treatment? I’ve read several fascinating articles on early trials of psilocybin in cancer (it dramatically improved patients’ emotional health)
In the PTSD field, psilocybin research has not advanced as far as MDMA research (MDMA is also called ecstasy). For patients with PSTD, MDMA can certainly help them feel good and help them talk/open up. But it seems as though that’s not the only mechanism at play. It’s also been shown to enhance fear extinction learning in rodents. It’s very worth studying but it’s important the drug is administered in a safe context. Both psilocybin and MDMA are fascinating areas of research. It’s too bad the USA still has a strong drug war mentality that makes conducting studies with these drugs much harder to do.
Me: Can you test for prions in patients with ME/CFS? In my last blog post I wrote about their antimicrobial activity (a topic I find fascinating).
Mike: No unfortunately my lab isn’t set up to detect prions. But I’ve been chatting with some folks about prions, here and at MIT. The antimicrobial activity of both prions and amyloid beta is kinda a million dollar idea. I’ll also send you a recent study showing that bacteria themselves can create prions.
Me: Aw too bad you can’t test for prions but send me that study!
Me: I should probably let you go…you have lots of work to do! Thanks so much for taking the time to talk.
Mike: No problem. Take care:)
I saw what you did there, Amy. Planting the prion idea in the unsuspecting researcher’s mind. (Hope it doesn’t infect his Vagus nerve.)
Haha Claudia your comment made me laugh out loud. Do you know Mike works in the same building as Robert Moir, who did the main amyloid beta antimicrobial peptide study? I told him he should walk down the hall and they should talk!
Also I interviewed Robert Moir a few days ago and his interview is going up next. It’s truly exciting to see these topics discussed in more detail, and more openly.
Thanks for your comment!
Please Please pursue this. We need answers. I got sick with a flu in 1993. I never got better. I was very active prior. Working full time, going to the gym, biking, snow skiing in winter, water skiing in summer, running….Had 3 children, husband, large house, very active in my church and my children’s school. Then could hardly make it up stairs, no restorative sleep, fatigue so bad could hardly wash my hair, chronic swollen glands, pain incomprehensible, memory near non existent. Went from being an admin secretary working with #s and data processing to not even being able to add or subtract my checkbook. This disease stole my whole life and family. Please don’t give up on trying to find answers.
Thanks for your comment. I’m so sorry about your ME/CFS. I know exactly how badly this illness can take away your life – having lived through the devastation myself.
There is no way we will give up on trying to find answers. What’s great is there are more research teams than ever committed to ME/CFS. Also, there are many new technologies that can help research teams better understand what’s happening.
Hang in there and thanks for writing,
I’ve had CFS for just on 50 years. Atypically, I don’t recall it developing suddenly after an infection. It has inexorably worsened over time. For most of that time it was made very clear that I was mentally ill, and I believed it and swallowed antidepressants like sweets. I have spent many thousands of dollars on supplements, chelation infusions, various prescribed drugs, long-term antibiotics, acupuncture, exercise and so on in a vain effort to find anything that might help. Of course, nothing made any difference. I’ve gradually lost my job, my marriage and my friends who thought I was a lazy malingerer. Not to mention my doctors, some of whom could not disguise their disgust with such a neurotic woman. My reputation was so blackened that ten years ago I changed my name and started again and have kept to myself without telling a soul, including doctors, about my illness. It’s lonely and depressing at times but at last there’s light at the end of the tunnel. Every time I read about the next step forward I can barely contain my excitement or my tears. To everyone who is doing their best to solve this mystery, thank you from the bottom of my heart – and please hurry 🙂
Your response is not long-winded at all! I just forgot to click the “approve” button on the comment. Sorry!
Thank you for sharing your story, because it’s also my experience that so many patients with ME/CFS lose their entire support systems, family…friends. One of my friends was disowned by his Dad for having the illness. Because of course his Dad was told that the illness was “all in his head.”
I’m so sorry you’ve suffered horribly dealing with this over the years. But I’m glad you can continue to remain optimistic. I agree that there is definitely hope for better research and maybe treatments in the coming years.
Hang in there,
My previous long-winded post wasn’t published so, from a non-scientist, thank you to everyone involved. Your dedication is much appreciated.
I am excited about the focus turning to the Vagus Nerve. It could be an infection but I’d imagine it could also be physical damage to the cord, nerve or upper cervical area either from an accident, chemical exposure or misalignment in addition to the possibility of a direct infection. Either way I think it’s such an impt area so I’m so thankful for this research!
How can we continue to follow up on the study and any findings???
Sorry for the delay in responding. It is very important research! Michael posts fairly regular updates about his brain scans and research on his Twitter (@MBVanElzakker). Also I know his group will publish their results after collecting enough data. I’ll try to keep people on this site posted.
I have been exploring at the Vagus Nerve and I would like to stay in your loop. I am not a reporter or doctor. Recently, I left work with memory problems that seem to be much improved now… then I switched dentists to uncover the fact that I have infections when I never felt any pain… then I have always had issues on and off with anxiety and depression… but being a introvert… I think I have discovered something that might be causing a total of three troubling areas along the vagus nerve. Please allow me to mention the 3rd problem that was chronic constipation for most of my adult life up to 10 years ago after getting a clear report for the 2nd time from a colonoscopy. So from head that might have a bacteria that crossed the blood barrier… I would like to learn more about studies on the vagus nerve that could be damaged in the neck area from high school days playing football, to injured front teeth at the same time that got infected over and over .. and then to how long I can stay on magnesium caps as my solution to having regular and good bowel movements… for many years. Head, spinal cord, colon and trying to keep an active lifestyle with a partner in good health ten years my senior.. God Bless for the best of everyone here. Jim