Inflammation Nation: Science Informed Wellness
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ABOUT
Dr. Steven Noseworthy is an internationally known Functional Medicine doctor and seminar speaker. Since 2008, he has taught thousands of doctors, of all kinds and from around the world, how to use a science-informed, systems-based approach to optimal health.
This podcast is a consumer friendly version of many of the topics he teaches in his doctor-only Functional Medicine seminars.
Inflammation Nation: Science Informed Wellness
177 | Unlocking the Neuroimmune Connection: Exploring Immunoception, Brain Lateralization, and the Insular Cortex with Experts Drs. Peter Scire and Rob Melillo
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Why is the brain's role in immune regulation often overlooked compared to its control over the gut and hormones? Join us on Func Med Nation as we tackle this thought-provoking question with our esteemed experts Drs. Peter Scire and Rob Melillo. Together, we navigate the intriguing concept of immunosception and its vital influence on neuroimmune communication, drawing from the groundbreaking research of Kevin Tracey. As we explore the brain's impact on the immune system, we raise awareness about the critical role of neuroimmune interactions and the potential "immuno homunculus," a proposed map of these connections.
Our discussion extends into the fascinating realms of interoception and brain lateralization. We uncover how the brain perceives internal bodily states to maintain homeostasis, linking these perceptions to emotional and developmental experiences. Discover how right-brain development during early childhood can influence immune function and self-tolerance, with potential implications for understanding conditions like autism and autoimmune diseases. Peter and Rob share clinical insights, emphasizing the need for a holistic approach that values clinical presentations over standard lab tests in diagnosing immune-related issues.
The episode concludes with an exploration of the insular cortex and its role in neuroimmune interactions. We shed light on the challenges of interpreting immune responses through lab tests, especially for complex conditions. By examining real-life case studies and the intricacies of brain-immune communication, we aim to inspire Functional Medicine practitioners to deepen their understanding of this interconnected system. Join us for an enlightening conversation that bridges neuroscience and immunology, encouraging a more integrated approach to health and healing.
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Hey everyone, welcome to the Funkbed Nation podcast. I'm your host, dr Steve Noswery. The views and opinions expressed by my guests in this podcast are not necessarily consistent with my own views and opinions. However, I do my best to be respectful of their views and opinions as they express them, even if they differ from my own. Now let's get to the podcast, okay, so let's go ahead and dive into this. Honestly, I've been waiting for this conversation with bated breath ever since we said goodbye on the last call and, just to give anybody listening a little bit of grounding, we've already posted two pretty lengthy interviews that I've done with Peter and Rob, and my hope today, guys, is to have more of a clinical conversation. I have posted both of our two prior interviews, on both the Funk Med Nation podcast as well as the podcast the Inflammation Nation, which is the general public, and I'll probably do the same thing because I, though, I want today, to be more technical and more clinically oriented. I think it's important for the general public to hear your name, see your faces and know that there are doctors out there that are thinking and operating at the level that we're going to reveal and share today, and the topic is immunosception. And then, as I had mentioned to you guys before, I want to start with a quote from one of the papers from Kevin Tracy, who's one of the big names behind immunosception research, and the quote is it's from a 2018 paper in Annual Reviews in Immunology and it goes like this it says the nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The brain integrates neuroimmune communication and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. And like there's so much just in that quote. Right, there's just a ton of stuff right there, but I want to open it up with a question and pose it, not rhetorically.
Speaker 1I really would like your opinion and your answers. But why is it that we, as clinicians, so readily accept the brain's role in controlling visceral function, like the gut, the pancreas and so on, and even, to a certain extent, the hormones? Because we recognize, for example, the adrenal system is the hypothalamic, pituitary, adrenal axis, and that tends to get forgotten, but it's still there. Why is it we have such a hard time recognizing or even accepting the idea that the brain controls and regulates the immune system. I guess almost like we treat the immune system as something completely different, almost a foreign entity. Why is that? What do you think that is Um? Why? Why is that?
Speaker 2Why do you think that is? Well, I'm going to say first of all, I I don't think that, like you said, people are really thinking that much of the brain regulating the gut. I still think people, you know, aren't thinking that way. I just did a lecture down in the Dominican Republic and I had two other doctors One was a functional medicine pediatrician, Dominican Republic and I had two other doctors One was a functional medicine, pediatrician and pretty good, and the other one was a neurologist who was a neuroimmunologist and you know she did a whole presentation on autoimmune encephalopathies and, you know, really went through it in pretty good detail, although it was the more severe type things and things that could clearly be measured in the cerebral spinal fluid. But everything both of their perspectives were that there's a problem in the gut, that this leads to certain issues that lead to inflammation, inflammation comes up and affects the brain and the inflammation in the brain produces a bunch of symptoms. So it was purely from a standpoint of going up and that was the neuroimmune piece.
Speaker 2And one of the things I think that we like about Kevin Tracy's work is he's one of the first people to come out and talk about the brain coming down and actually regulating and being the initiator, and I think there's so much, like you said in that quote about that.
Speaker 2You know, in the periphery, in the peripheral sentry nerves, just like we pick up pain and inflammation, so we have inflammation in our body, in our joints, we feel it in our brain.
Speaker 2That also is. There's immune signals that travel similar pathways that get to the brain and then the brain is going to respond from a top down standpoint and have some regulation. And I think you know, peter and I have gone about through this because you know the immune system is incredibly complex and as we discuss it and you know there's some really good people and they really describe how everything is and it doesn't seem like anything's missing from that piece on the overall. And so I think that's the thing is that you know the immune and the immune communication within the immune system is pretty well documented, even though there are gaps that we've picked up on. And so I think it's easy to get lulled into the thinking that the immune system operates completely independent and that it may create inflammation in the body that affects the brain. But there isn't, I think, very many people that have the knowledge of the neurology to understand the downward influence and control that the brain has from the brainstem and from the brain itself, and I think that's where the gap is Peter.
Speaker 1what's your opinion on this and your feedback?
Speaker 3Yeah, well, one. You know. Keep in mind that the psychoneuroimmunology community has only been around, I think, maybe at best not even 30 to 40 years, okay, when they really started and Richard Adler and a couple of those people really started looking at this. And so, you know, for the longest time these super systems I mean they've referred to that in many papers like the immune system in the right hand and the nervous system in the left hand, were just separate of each other and there was. And now obviously, like Kevin Tracy points out, that we now know, and you know I remember Rob and I were sitting in his house a couple of months ago looking at that same quote and saying, okay, hey, we're getting the toll-like receptors talking to the brain, we got these cytokines talking to the brain, we got these chemokines. And you know, for a long part, you know, of classic education no one was really talking about. They were just saying, ok, these are these inflammation or these inflammation aspects of inflammation, or these ways that we're telling the immune system to do this. But, as Rob's pointed out, it's like who's the conductor, who's signaling to the immune system to do this?
Understanding Brain's Role in Immune Response
Speaker 3And I think that the biggest thing is I came across a new paper a couple days ago, where it's probably a 2019, 2020 paper, I think, that was now looking at the role of the brain in the innate immune system. Was now looking at the role of the brain in the innate immune system? Okay, and they're actually. We're studying frogs and looking at actually taking frogs and separating the brain to try to figure out, you know, what happens if they disconnect the brain to the immune system and they they put it, you know, a they were using E coli as the antigen to see what happens and what they found out that was, if the brain wasn't present, they wouldn't get macrophage differentiation. Ok, there was no way the macrophages would actually maybe split to an M1 position or M2 position, and so I mean, there it is, and the paper was talking about how we've studied, you know, a certain amount of the brain to the adaptive immune system, but we really haven't begun to really explore the role of the brain in the innate immune system, and I think that's where I think you know you talk about where the literature is going.
Speaker 3I think that in the immunosceptive world I think that's what we're trying to understand now is more of what's the brain's role on the immediate immune response to recognizing the different toll-like receptors recognize. How's that signaling to the natural killer cells? What's that telling the macrophages to do? But you know, trying to understand what particular anatomical areas and I think the major thing that we're going to be looking at over the next couple of years that gets lost in some of the translation is Kevin's Tracy whole idea of the immuno homunculus. Okay, and really getting to look at these definitive areas in the brain. I mean we've talked about a sensory homunculus, a motor homunculus, but now can we actually begin to fully put that together? I mean we've talked about a sensory homunculus, a motor homunculus, but now can we actually begin to fully put that together? I mean that's a hypothesis that he put together about 10 years ago and I think now you know we're trying to unravel that.
Speaker 1Yeah, let's hold on to that one because I think we need to work our way towards that. But you know, for clinicians that are listening, they'll remember back in their early training days they learned a little bit about sensory, homunculus and motor and how we have these maps of our body up in the brain so the brain can understand. You know how to connect to different pieces and parts. You use the word immunosception. I'm going to ask you in a second to back up, but I want to share with you.
Speaker 1I did a webinar for Vibrant Labs, probably three weeks ago, and the topic was an effective clinical model for complex disease, complex clinical cases, and I shared with Vibrant and all the people that were listening the clinical model that I use. And this is going back to what you were just saying about the brain is the top dog and everything is interconnected. And I started by quoting Tomi Otada, who was the guy who coined the phrase super system back in 1997. And so I put up a graphic that showed the brain, hormones and immune systems, started drawing these connections and even now, like going back and looking at that, it's very easy for me to draw out and to map out connections on the neuroendocrine side, right, it's easy for us to even kind of dissect the brain, so to speak, and look at the lobes and look at networks and how things interconnect. But the part of the diagram that represents the neuroimmune interactions is kind of sparse, right, and you know, I'm certainly no expert in this area.
Speaker 1I think I know a little bit more than the average clinician, but I'm no expert in this field and I'm struggling to put that to like to fill in that side of the graphic and I'd be happy to share that with you guys and get your feedback on it. I would love your feedback, actually, and maybe I'll put a link in the episode description that people can go to the web and look at that. But it's so, as clinicians, it's so helpful to have a roadmap, right? And what I'm hearing from you is that maybe this is where the research is going. It's just like we have a roadmap from the brain to the motor system, we have a roadmap from the brain to the visceral system and so on, that maybe we'll have a roadmap to the immune system, right. So, pausing that idea, and I'll toss this up for either one of you guys define interoception, contrast that to exteroception and explain to me to us why it's so important for the brain to understand and have an interface with both internal and external environments.
Interoception and Immune Regulation
Speaker 2Well, interoception is really the ability for the brain to perceive what's happening in the body, really from a homostasis standpoint, and this is really critically important because, from the time a child is born and we know that that right hemisphere is active, more active in the first three years. So, when the child is born, non-verbally, they need to be able to perceive and express to their parents or caregivers, you know, when they're in pain, when they're hungry, when they're thirsty, when they're cold, when they're hot, when they need to be changed, you know, or if they have gas or something going on in their stomach, when they're tired. And smell and taste are very much around this right. So we need to be able to feel those things or sense them right from the beginning for survival right To be able to know when something is wrong, when we need to eat, when we need to drink, when things are too hot, if I'm in pain. All of that really is registered in the right brain and all of it is registered primarily in the insula on both sides, but finally in the right insula and the right brain is online, you know, early on in that in reason, and we need to be able to do that because, obviously, again, as the brain is maturing and as we're building from the bottom up the, you know, whatever, whatever little seeds start in the brainstem as the precursors ultimately grow up and create different areas of the brain, so then the brain can come down and regulate everything, and that's the way you know it's supposed to work. That's the way this whole complex system works.
Speaker 2We need to have, you know, this kind of internal map of our body and proprioception the ability to know where our body is in space and feel our body and creating these sentry maps also starts in that insula area, so that all of this kind of is in that area there, and it's very important. And so you know it makes sense to us. We think about this but we don't think about, well, what does that look like? Meaning, what areas of the brain are registering this? As you said, what are the networks from the bottom up that transmit this information?
Speaker 2I think there's a lot of overlap with the neuroendocrine, the neuroautonomic system and the immune system, because if you hear what Kevin Tracy said, he said basically these efferent top-down pathways through the autonomic system, so through the balance of the sympathetic and parasympathetic.
Speaker 2That's what regulates the immune system and I think he's done a fairly good job of even talking about the input from the sympathetic and parasympathetic into the actual immune tissues and how it actually, you know, may start the process of what's going on in the lymphatic tissue to, you know, start this process. So we do have a fairly good map of this from both the afferent and afferent pathway both the afferent and afferent pathway. But interoception is really critical for that because also all of our right brain emotions and most of our emotions are built on top of that. So first we sense things and then we start to sense feelings that are superimposed on those and then we're able to read those same things on other people and that's the foundation of nonverbal communication and socialization and ultimately, emotional regulation and attachment, and then that leads to the desire for verbal communication. So this whole idea of being able to survive and be around other people and all really starts with interoception and what we see is that, I think, is the biggest piece missing in severe autism, in nonverbal autism.
Immunosensation and Autoimmunity
Speaker 1Peter, I think that you and I probably have the same mindset on this and in fact I was just in San Francisco last weekend teaching our brain chemistry course and I really made a big effort to try to change the framework, like the conceptual framework, of the docs that were there, and not just go through the standard material that we presented for 15 years, but do it, you know, kind of in light of some of the work that you guys are doing, and attach it to developmental, neurodevelopmental issues and so on. And so with this concept of interoception, which is immunoception is one component of that, like some very common clinical manifestations of interoception would be, you know, someone having their blood sugar drop and then triggering some kind of an anxiety event, right, and I don't know that. There are many clinicians that make the connection that it's actually the brain that's causing all of this. Right, they think, well, it's an adrenaline dump and that's why. But really still it's, you know it's driving in the brain. So we have all kinds of different types of interoception. Rob, you mentioned a whole bunch of them, like hunger and thirst and temperature and all these different things. But we also have these chemoreceptors that sense the constituents of the blood right, Glucose levels, hormone levels, all this kind of stuff.
Speaker 1And now? So let's focus in on this concept of immunoception, Peter, and I know that this is like your deal Of course you're a more well-rounded, you're not a one-dimensional clinician, but this seems to be like a passion project of yours is to really understand immunoseption and bring that into the world of functional neurology. So define it in maybe more discrete terms than what we've defined so far and what I'd like to get at. Rob, you mentioned that this happens. It's mediated through the sympathetics and the parasympathetics, and you also mentioned the insular cortex. So where does all of this stuff happen? Is it a discrete network? How highly organized is the system? How predictable and reproducible is it from one person to the next? That was for you, Rob. I'm sorry, Sorry, sorry, sorry, Peter.
Speaker 3Go ahead.
Speaker 3Well, I mean, I think, for starters, I think the challenge for me right now is trying to figure out, like, how do we measure some of this stuff right? How are we measuring the different relationships of the immune system? I mean, I think that's where you know I'm looking at. When I'm looking at a client, you can obviously see like sickness behaviors. Sickness behaviors you could begin to see how people are perceiving their reality, of their, you know, somebody with anxiety, or somebody with depression, or somebody comes down with a cold and you know they adopt these behaviors that, oh, I'm feeling sick today I'm going to go lay down, you know, I feel. You know, once we have these things where we say like, oh, I feel like I'm getting a head cold, OK, well, how do you feel that? Well, that's the whole idea of what interoception is, and this immunosception component of it is that I'm getting these, these signals that are coming from my body. Or, you know, I sprain my ankle. Ok, you know, can you? You know, sometimes you don't have to just look down and see that your ankle is swelling, but you actually can perceive that, hey, I'm hurting, I'm feeling pain, and so I think that you know, trying to get patients to understand that you know one, when we have, when our immune system turns on and begins to activate, it's going to go through these very stereotypical responses.
Speaker 3And I think that that's where some of the immunodeception research is going is that we have these very specific responses that the immune system makes, and makes it in a very stereotypical way, very much like our motor system does, Like we have our motor system that does these particular outputs that are somewhat reflexive, or we know that they're reflexive, and then over time we can build a complex motor task and that in itself becomes a very learned response.
Speaker 3So I think that that's what we're seeing in the immune system is that we're now seeing this choreography that happens within the innate immune system and the adaptive immune system, where, when we engage ourself in a certain type of response to maybe a pathogenic response or we're dealing with some damaged tissue and we're getting a damp response, that we're going to have this very specific response that the immune system is going to coordinate using a various amount of cells that are in the innate immune system or calling on the adaptive immune system. But then what happens is that then the immune system now makes this memory of it Okay, so that way, when it happens again, we now can mobilize much faster.
Speaker 3And this is not necessarily like talking about our adaptive immune system and our antibodies being made.
Speaker 3We're talking about the choreography of all the responses of the immune system that happen to that given moment of tissue damage or a pathogenic response. In that aspect, and I think that's what we're beginning to figure out about this whole concept of immunosception is the idea of how it's all choreographed, okay, and how you're seeing. You know what cells that are coming online at certain moments, and I think you know back to how we do things in movement. You know we know when we go to move our body in a certain way, we know it's going to involve our cerebellum and what parts of our cerebellum and our basal ganglia and our frontal lobe. So now you know, when we encounter a certain pathogen or a certain inflammatory response, we're going to get this very stereotypical choreography of the immune response and then the immune system is then going to in the insular cortex, going to have these kind of like files that they have now and they know that. Okay, we do this immunologically when we encounter this, and that's how I'm looking at explaining the concept of immunosuppression.
Speaker 1Right and you and I did just the two of us we did a couple of interviews on one of the podcasts and we talked about we use the word engram right on one of the podcasts and we talked about we use the word engram right, which is that brain's memory of some kind of a peripheral immune event, whether it's an injury or something like that no-transcript in the traditional way that memories are stored, or are they stored in the insular cortex. Is this a completely because it's immune-based memory. It's not like cognitive memory, it's something completely different but it's memory nonetheless. So is this interlinked with, or is this completely separate from our, let's say, our traditional memory systems?
Brain Lateralization and Immune Response
Speaker 2I think it's within our traditional memory systems. But remember, we have different memory systems between our left and right hemisphere. The right hemisphere has more of a subconscious, unconscious memory, where the hub of it is really around the amygdala, which is really more of an emotional type of memory or experiential memory. We remember what something feels like but we don't recall it as a memory, whereas factual memory, episodic memory, declarative memory, conscious memory, is really generated more through the left hemisphere hippocampal networks. So I think it's within those systems. But I think, like most right hemisphere memories, it's implicit, it's subconscious, it's not something that we consciously say oh, this is a memory. But our body responds to something as a memory, meaning we know that it's there, like we've been hurt once before. That's what happens in trauma. Trauma tends to live in that right brain. Happens in trauma Trauma tends to live in that right brain and even though people may not remember the memory of the traumatic event exactly, that, it can get triggered over and over and over and over again. Or if they have a memory, that's literally a flashback where they literally go back to that moment.
Speaker 2But you know, one of the things that I think is cool is again, with the interoception. You asked what was important about that. Well, again, that, and the insula and the anterior cingulate is where we become embodied, right, that's where we become an individual person. We become self-aware. One of the most unique features of human intelligence is self-awareness, right, meaning that homo sapien sapien, the wise man that knows he's wise. It means that level of self-awareness is what is unique to human intelligence. Right now we don't believe, ever believe, artificial intelligence will have that. But that's the fear that they may someday become self-aware, right, but without a body. The belief is you can't become self-aware.
Speaker 1Yeah, you can't be embodied if you don't have a body.
Speaker 2Exactly. And you can't be self-aware if you don't have a body and you become embodied in that insula and that's where you recognize yourself from other Around. Two years of age, your child suddenly recognizes themselves in a mirror. Now, if we look at autoimmunity, what's the concept of autoimmunity when you lose, when the immune system loses, the ability to recognize self?
Speaker 3from other.
Speaker 2So where would that and where would the memory of that or the concept of that be regulated? In the same area that we understand our self from other as a body, we also understand our immune system from self from other, and so you look at that and say if there's a dysfunction in one. When you have lack of interoception, you often see, you know this very high level of autoimmune reactions eczema, food sensitivities, pans or PANDAS reactions, you know autoimmune encephalitis and all of it is really related to that regulation of those things.
Speaker 1So, if I heard you correctly, the right brain and you've said this many times in your interviews that the right brain develops preferentially right in the first three years of life. It's not that the left brain doesn't develop, just the right brain develops more efficiently and faster. And the right insular cortex and, I would imagine, to a certain extent, the parietal lobe, because they would have to communicate together to have this sense of self. What I'm hearing you saying is that that has influence over what we would say from a functional immunology standpoint, the concept of self-tolerance, and when we lose self-tolerance we start to generate autoimmunity. So I guess what I'm trying to ask is how predictable are these relationships Like the right brain controls or generates tolerance, and when we lose that, we lose tolerance and we have the expression of autoimmunity.
Speaker 1Is that always a right brain or right hemisphere function? And if that's true, what is the left brain responsible for? And again back to a question I asked before how repeatable and reproducible is that from person to person? Is this part of our developmental blueprint, meaning that it's predetermined that those parts of the brain are going to control these aspects of the immune system, or is that much more experiential, like developmental from the standpoint of as I have lived and experienced these inputs into my system. My immune system and brain have developed this relationship and it might be different from somebody else's.
Speaker 2I mean, I think personally because the insula is online so early. These are all developmental. So even when we talk about the right brain and the left brain becoming the right brain and left brain, it's almost all experiential, it's almost all non-genetic. That's what makes the right brain the right brain and the left brain the left brain. The timing of it is what makes the difference right and I think it's very, very predictable. But what we often see is that when something alters that timing mechanism, it may alter how the brain is developing and regulating itself and that is what leads to these different developmental imbalances that we see. So I think it is very reproducible from a standpoint of that.
Speaker 2You know, we know that the right brain will in general, if it develops appropriately, will do things. It's more involved with bottom up. It's, you know it has a lot to do with, you know, proprioception and feeling our body. And there is an overlap, as you said, with the parietal lobe, because the insula parietal vestibular cortex, the border of the insula and the parietal lobe, is the primary vestibular cortex on the right side, which again helps us to develop a vestibular and sensory map as well as a somatic topic map. So it is reproducible and so it is predictable, and so, therefore, we can use this to actually change things. But when this is altered in some way, that's where we see a problem, and it's almost always from a developmental perspective that this is altered.
Speaker 1So I'm sorry, go ahead, peter.
Speaker 3Yeah, I think to Rob's point. You know, one of the things we've seen over his career and what we've seen over my career is when you look at these kids and you look at these developmental imbalances, there tends to be these almost like trademark symptoms that they have.
Speaker 2That you know, we look at autism, for example.
Speaker 3We always see for the majority of cases, if not all of them, you know, under development in their GI system, in their GI system, so many of them have upregulated atopic presentations of eczema or skin rashes or history of that, and then they tend to be a, they get an immune response and, you know, is it enough to knock down the infectious agent or it lingers more and they don't get a contraction of their immune response. And so I think that that's you know. And when you look at the laterality research, I mean the research goes back 30 years. Unfortunately, the major brain laterality research for the immune system passed away several years ago from cancer and unfortunately not many people picked up his work. But you know, the basis of it was that you know, the left brain tends to be more the activator of the immune response and the right brain tends to be more the inhibitor of that. And I think what we've seen over the years is that when you have a more dominant left cortical development, especially a progressively early onset of that left brain development, okay, you know, are we seeing these higher instances of autoimmune types of presentations with these young children? And our experience has taught us is, as we start to establish more right brain dominancy of the immune response. You know that we tend to bring that back in line Now. There's definitely some nuances that now to where we look at the T cell positions a little bit different than we did maybe 20 years ago, and the simplicity of the, the t-helper cell one and two and three and th17, you know now we know there's some subsets, so there's definitely got that has to be accounted for a little bit more in a way differently than we've done in the past. But I think that from a totality of what I've seen and what rob's seen, is that you know, a lot of these kids tend to be classically more Th2 dominant or classically Th17 dominant. They don't have a very, very strong Th1 response or a natural killer cell response and you know, and especially if their Th2 system is really revved up, they're going to have more autoimmune expression. And you know, one of the things that I've been teaching, now that you know Dr Yannick's been talking about for quite a while now, is the whole idea of, like, an increased Th22 expression, where you now you get, you know, high level of glycation of antibody expression so that they make the antibodies more stickier, and so then do we get a more activation of these antibodies, especially in the basal ganglia that we may see in the PANS presentation.
Speaker 3But I don't think the answer is just purely trying to promote a polarization shift. I think that's part of the answer. But the bigger thing is this top-down modulation of the immune response and trying to get that right brain to come online more so we do get a more developed gastrointestinal system, so that every child that we treat doesn't have to stay on, you know, glutamine and dry licorice and all these products for years and years and years to try to treat their gut. Because what is, you know, if you're looking at this from like Rob's point of view and saying, okay, you know, are we looking at this autonomic dysfunction and are we looking at really more a heightened sympathetic response and the fact that the parasympathetics tends to be seems to be more governed by the right side of the brain, Okay, so if we're shifting towards a left-sided early development, do we get increased sympathetic outflow and obviously we're seeing that decreased parasympathetic aspect.
Speaker 3So I think for us, you know, I think our database is much different than most people and I think that's why we can be probably very more convicted to say listen, you know, you fix the laterality, you address the laterality to say listen, you know, you fix the laterality, you address the laterality. You are going to address downstream neuroimmune consequences. And we do see children, you know, do better with gut function and do have better overall intestinal function. They don't seem to get intestinal inflammation quite as much, they don't seem to have to constantly be on guard for so much contamination to food responses because their system does finally calm down.
Speaker 1And is that the brain work that you're referencing there and the changes in gut health and function? Is that with or in the absence of, say, nutraceuticals that are designed to get rid of infections or support healing? Permeability issues?
Speaker 3I think you know from, my approach has always been you kind of using those as a modulating.
Speaker 3You're modulating the immune response, you're trying to modulate the T cell polarization and you're trying to maybe cut down on the gut inflammatory stuff. While you're trying to maybe cut down on the gut inflammatory stuff, while you're trying to build the brain, okay, and but as long as you cause, if you do nothing but just do that like most of the functional medicine world, we see it all the time their parents are walking in on supplement after supplement and they haven't changed that immune response or they haven't changed that gastrointestinal development because they haven't done the bottom up development of the brain and then getting that bottom up interference out of the way. So that way now you can get those higher cortical networks to finally come on and do their inhibition and maturation of certain areas. And so I think that's the biggest thing is that, yeah, you do those. We use these T cell supplements and way we're trying to modulate the immune response but to quote unquote get a more permanent effect, it's got to come down from the maturation of that right hemisphere.
Brainstem Influence on Gut Health
Speaker 2I think a good practical example, steve, is kind of jump on what Peter was saying before. You know, most of us know, like I mean, we've all experienced where we go. Oh my God, I feel like I'm getting sick. My throat starts to get a little thicker feeling and I'm just not feeling great Right. And that leads to what we call sickness behavior Any behavior for us to be able to perceive that it has to be happening in the brain.
Speaker 2Absolutely. We have to register that where somewhere we go oh, my throat doesn't feel good and I'm not, and I know I'm getting sick, and so the immune system and no one's ever really thought about that or really said, oh well, ok, so we must be perceiving it in the brain. So then the brain is going to react some way. That's what it does, right, it feels things and then it reacts. And that's what Tracy's work was really, I think, really on the forefront of.
Speaker 2But he still stayed kind of low down in the brainstem and the lower part of the brain didn't really completely bring in, you know, the upper part of the brain as much like the orbital frontal cortex, which plays a role in that and and other things that play a role in it. But you know, it's just for somebody to think about it like you know, okay, your stomach doesn't feel good, or you ever had a chance where you ate something and you just didn't feel right, and then you know a few hours later you're puking your brains out, but right, as soon as you ate it you didn't feel right. Right, you perceive that somewhere. We have to perceive it in our brain, and where we perceive it is in that insula and in the humunculus.
Speaker 1If we can localize it, it's in our humunculus, and then there's an efferent reaction to that and there are pretty well-known pathways that we know that do all of that, rob, I'll direct this to you because I made the point when I was teaching in San Francisco that there's so many cases and I'm not talking about kids on the spectrum right now, but just generally across functional medicine clientele that people come in and they have a leaky gut, they might have an altered circadian rhythm, and we do some supplements, we make some lifestyle adjustments and those things sort themselves out.
Speaker 1And I made the point that whenever you are doing what you think you know to be right from a nutraceutical, dietary, lifestyle standpoint and you get these resistant patterns like you get the leaky gut that either never goes away or always comes back resistant patterns Like you get the leaky gut that either never goes away or always comes back, or you get that abnormal circadian rhythm that just doesn't smooth itself out with the standard practices. I made the point like you've got to think about the brain in those circumstances. Would you agree? And how might you modify that sentiment?
Speaker 2Yeah, I think you know from the very beginning. You know, when I was down there in the DR and listening to these doctors, they both did a good job and it really started with there's this problem in the gut and there's a leaky gut and there's intestinal permeability and there's a breakdown and there's not the production of enzymes and acid. But my question is okay, well, why is there a leaky gut beyond a certain age and why aren't they producing these acids and the enzymes? There's a step and that's where I think it starts in the brainstem. The brainstem is not coming down from the beginning and the gut starts out leaky and open and the sympathetic nervous system is on full when we're born and the parasympathetic nervous system isn't. So that's how we start life.
Speaker 2And if somebody's still like that, where they still have a leaky gut, they still have a sympathetic dominance, they're not producing the parasympathetic then it most likely starts in the brainstem because that nuclei that would regulate those things, the nucleus ambiguous of the parasympathetic nervous system and the nucleus tractus solitarius, isn't developing to begin with, right. So it's not that that happens to the gut. The gut just isn't maturing because the brainstem is not maturing. So, right from the beginning. The idea that it starts from the gut and works up is false. It starts in the brainstem and it goes down.
Speaker 1Yeah, I'm sorry to interrupt. I just had two thoughts as you were going through that. We know that babies are born with a leaky gut and that goes away spontaneously as long as things develop. That's the key there, steve yeah exactly, and so I don't know the answer to this, but at what neurodevelopmental stage does that newborn leaky gut resolve, if you know?
Speaker 2When the nucleus ambiguous comes fully online, right, it's a parasympathetic response as we start to eat food and as we start to have a need to digest food and absorb it. Now we start the rest and digest system, which is the parasympathetic, which is the nucleus ambiguous. Before that we have the rostral ventral lateral medullary nucleus, which is the sympathetic nervous system, and we have the dorsal motor nucleus of the vagus, which is what starts it all. Right, but ultimately, the nucleus ambiguous is what causes the gut to close up. It's what produces or allows for the production of, by either inhibiting the sympathetic nervous system or activating the dorsal motor nucleus, where we're producing digestive enzymes and acid in the gut. So that's where it starts on the way down, and that doesn't happen if that isn't maturing, meaning a child still eating food.
Speaker 2But it's not just the eating of food that causes it to close up, because if that was the case, then no one who's eating solid food would have a leaky gut, right, because that's the point. So there's something other than that that isn't developing, even though now we're eating solid food, but yet we're not closing up that gut, we're not producing the enzymes, we're not producing the acid and we're not increasing the blood flow to the gut for absorption, and this is everything you see in kids with autism and this is everything you see in kids with autism and this is everything you see in most kids in the neurobehavioral spectrum, especially with the right hemisphere delays.
Speaker 3And I would add that you know the relationship of the orbital frontal system to all that. You know that one of the things that we constantly see is that they have suppressed the output of their orbital frontal function. And so, and as Rob was saying, this early development of that orbital anterior cingulate insular mechanisms that are happening in that first year, you know, first, 18 months of life, you know 36 months of life and so I think that's you know, when we look at kids with autism, they don't smell, most of them don't have any sense of smell. You hold up a canister and you ask them to blow sniff in. They don't sniff in. Parents will talk to you all the time they don't relate, the ones that are even verbal, they don't talk about smelling mom's cookies or come into the kitchen and say, hey, you know what's cooking today. You know that smells really good, okay.
Speaker 3And then you look at the orbital frontal relationship to self-regulation and being able to, you know again, modulate those internal visceral states of being Okay, internal visceral states of being okay. That you know again, you know we all get upset or we all can get anxious. We all can get, you know, a sense of I want to go towards something very aggressively, but you know what hemisphere really begins to regulate all that is the right hemisphere and more specifically, the right orbital frontal, and so, as Rob has been talking about this idea of embodiment, attachment and self-regulation, it's all coming from the right side, and so I think that we're going to continue to probably find out. Not only is the right insular cortex a major player in the immune modulation, but I think we're also going to probably uncover that the orbital frontal area has a lot to do with this immune modulation as well.
Speaker 2And we can map this out from the bottom up. I mean we can kind of go through that yeah let's do it, okay.
Speaker 2So again. So in the periphery, as Tracy talked about, we have these peripheral nerves that are in our tissue and sensing. We have an infection, we have inflammation, we have something going on and just like we perceive pain, we perceive that there's inflammation going on, we perceive that you know what's happening, we perceive the presence of these foreign invaders through the sentry neurons and all of that afferent input really comes through the vagus nerve. There was a recent paper recently that showed that the use of probiotics had a direct relationship on activating the vagus nerve right. So from there it goes up and it goes into the solitary nucleus in the medulla, in the brainstem, and from there then there is a regulation of, like I said, the rostral ventral lateral medullary nucleus, which is the sympathetic, the dorsal motor nucleus and the nucleus ambiguous right. So from the NTS it's going to go to those areas and it's going to feed information to either activate the sympathetic or parasympathetic there. But then from the NTS it goes into the parabrachial nucleus near the dorsal vagal complex. From the parabrachial nucleus that goes to the paraventricular nucleus of the hypothalamus and again, what they showed was, with probiotics, when it activates the vagus nerve, that goes to the paraventricular nucleus and can cause a release of oxytocin and vasopressin. But also that's the start of the HPA axis, which is an anti-inflammatory pathway. But then it goes up from there into the periaqueductal gray and then it goes to the amygdala and then it goes to the anterior cingulate and then it goes to the insula and the orbital frontal cortex and then from the orbital frontal cortex ultimately will come down and generate much of the efferent control along with the insula. So we go up and we see that, as we said, this is called the central autonomic network.
Speaker 2It's a network that's been mapped out, we know it exists and that's also that peribrachial nucleus is also where we initiate sickness behavior in the brainstem. That's where it starts, so getting a fever. You know we have some people, some kids, on the autism spectrum that when they get a fever they start speaking. I believe the reason why many kids don't speak is because the lack of that insula and interoception and proprioception and not having a map of their body and not having that drive to communicate and not having that drive to communicate.
Speaker 2But it would be interesting because when they get sick and they have inflammation it ultimately gets picked up through the parasympathetic nervous system in the vagus into the insula and the right insula, activating it, and now they feel their body better too and they speak, and then that initiates the HPA axis, which is generating anti-inflammatory and it's generating the corticosterone, which is our own most powerful anti-inflammatory system. So that's the way this network works, and the left hemisphere is more activating through the insula of the sympathetic nervous system and the inflammatory, pro-inflammatory cytokines and pathways, where the right hemisphere and the right insula is more through the anti-inflammatory pathways. And that is the way we see it working right now.
Brain's Influence on Immune Cells
Speaker 1Peter, on that last note, with pro and anti-inflammatory systems, do we have it? I remember back when I first heard about this brain immune connection, people were talking about lesional studies where, for example, the one that sticks out in my mind is if you damage the cerebellum, you lose your natural killer cell population, for example and I don't know if that's been borne out or if that was a theoretical model. But is it a circumstance where, going back to a very simplistic T helper cell model of TH1, th2, th3, for example, if the right brain, particularly right insular cortex, is anti-inflammatory and gives us tolerance, would we expect that part of the brain to have more control over TH2 systems, over regulatory T cells, for example, over TH2 systems over regulatory T cells, for example.
Speaker 3I think we're still trying to dissect that all out. Because, again, I think that when we look at, for example, we know that the TH2 system for a long time was considered like this anti-inflammatory system, but yet it's. But when it's overactive it can really be super inflammatory. Right, it can. It's driving more of these atopic presentations, it's driving more of these asthmatic aspects. Okay and so. And then in the presence of a real dominant th2 response, where you're pumping a lot of interleukin 4 out OK, and then you're also pumping out IL-5, IL-13. If you get intestinal inflammation, you can pump out, like TSLP and other interleukins that are going to even promote a greater shift of that TH2 system, that are going to even promote a greater shift of that TH2 system. And then from there, if in the presence of a bunch of IL-4 and TGF-beta do we shift over to a TH9 expression and that may drive more of a mucosal response, Okay. So I think that's where you know, where I'm at least trying to process through that a little bit, Okay, To kind of say, because the way I'm looking at it now is where you know, where I'm at least trying to process through that a little bit okay, to kind of say, because the way I'm looking at it now is that you know, a lot of these kids are coming in with more of a Th2 dominancy to begin with. Okay, so what's driving that Th2 dominancy that we see where we have the asthma, we have the atopic presentations, okay, we have the over responsiveness to seasonal allergens and stuff. So we tend to see that. And then you know, when you do have a, you know, a higher level of a TH2 system, you're going to kind of basically stop autophagy and mitophagy in its tracks and you're not even going to be able to promote as much of a TH1 response. So now you know, do you get a bit a bigger burden of of this bacterial situation in the gi system where now you're, you're, you're allowing that bacteria to go and you got more gut dysbiosis? Um, you know, maybe you're getting more viral load burdens. That are going on.
Speaker 3And and then you, the more aspects you get. Because the one thing that we're seeing with the T cells, it's not they, they can morph in and out. You know it's based on the cytokine presentation that they have that they can be dumping. If IL-4 is really present, it's going to, it's going to shift that naive T cell to to TH2. But if all of a sudden IL-6 comes floating along, IL-6 is going to shift it to a th17 system. So I I think that I don't want to be linear yet in that, in that construct I think that we still have to unravel that a little bit more. To try to see now with how you know how rapid and again the idea that it's not like your whole body is systematically Th2 dominant. You're having it in very localized areas.
Speaker 3You could be needing a Th2 response in your nasal pharynx, but in response to a fungi you need a Th17 response in your GI, system response in your GI system, okay, but I, but I think where we're looking at, at least, is the perspective of are we shifting to where those systems are too dominant, okay, too overexpressive?
Speaker 3Now the question is, how is the brain not regulating those two systems? I think that's the bigger question for us now is trying to figure that that we know that we can shift into a TH17 dominancy, we can shift into a TH2 dominancy. We can lose the integrity of our TH1 system. Okay, we may not have enough of that T regulatory, that TH3 that we used to call, but now we it's really dominantly called t regulatory system, but we lose some of that integrity of that system to modulate. But, um, I think for me it we're trying to figure out how to pull it back but then at the same time, probably really relying on that right brain to come down and calm down the th2 and the th17 systems yeah, I think that the way you describe that is that you know you can have, remember what.
Speaker 2How do we know what's happening in the blood?
Speaker 2We draw it out and we look at it outside the body.
Speaker 2So typically we test blood not in the presence of the nervous system and if we did would we get completely different responses but also, as Peter's saying, you know if you can have an infection or something happening in one area and then a different one in the other and you need different immune responses.
Speaker 2You know the immune system and the metabolic system usually isn't that specific, it's usually more of a globality. When you need specificity, you need the brain to regulate it. You need some sort of like somatotopic map in our brain, like a humunculus of our immune system that would say okay, I'm perceiving this in my right shoulder and I need to do this there to the immune system. And the immune system and the brain can regulate the release of these cytokines so that it promotes more of an inflammatory response here or maybe an anti-inflammatory response here, and that they're like neurotransmitters being released or being modulated by the brain modulating the release of those cytokines which is orchestrating what's happening in the T-cell polarization and what they're doing and where they're going and all of that. So I think the fact that it may be that specific just speaks to more and more that the brain has to be taking the main role in.
Speaker 1So is the primary role of the brain in the neuroimmune axis. Is it to assist in T-cell polarization, to shift the population of different types of cells, or is it to change the behavior of cells that are already there, to make them more active or less active?
Clinical Challenges in Immune Testing
Speaker 3I think that's a great question. I think it's probably both, to be honest, I think that you're trying to because, again, especially with these T cells now, I mean we're finding out they're not static, right, they can change on a dime. And then they can, let's say, you go from a naive T cell and you shift to a TH2 cell and that effector cell relationship, but these effector cells over here can then change on a dime to another T cell position, right, based on the climate of what's happening and and really you know, based on the signaling probably from the innate immune system, and how antigen presenting cells is happening and what is the co-activation that's happening there and what toll-like receptor is presenting that relationship that changes the morphology of that T cell. But again, I think that, as Rob has said, is that I think the elegancy is going to be here, the idea of how the brain is signaling down, and I think we're going to see some breakthroughs in how the brain is telling, because the innate immune system is giving the instructions to the adaptive immune system, right. And so we now, I think, are trying to look at what is the brain doing to the innate immune system, and I think Kevin Tracy was beginning to kind of and his team there were beginning to put some of the understanding to okay, what can happen with a certain macrophage or what can happen to a certain neutrophil, or this whole classification of innate lymphoid cells that you know have just been discovered over the last, say, 10 or 15 years, that we're barely beginning to understand what they do Like.
Speaker 3We have innate immune lymphoid cell one, two and three. One tends to be associated with a Th1 system. Innate lymphoid cell two tends to be associated with Th2. And Th3 tends to be the innate lymphoid cell three. So I mean that's a whole other scenario now. So again, I think that we're going to be starting to see where we're going to understand a little bit more of the way the brain is discreetly instructing the cells of the innate system to do what they need to do and then how they're going to go and then tell, ok, the T cell system to do what they have to do or the B cell population to do. I think we're going to have a much clearer picture on that over the next couple of years.
Speaker 2Yeah, what you just raised, Steve, was really our primary question around research. Right now We've come to the same point. We're like, wait a second, ok, and nobody that we're aware of yet has really answered that question that you just asked. And it's really great that you got there because, again, you only because you have a lot of knowledge. You're like, ok, yeah, so this and so we don't know the answer to that yet, but that's where we want our research to go.
Speaker 1And we think you know that4, cd8 populations for decades, right, and then in the last, say, five to seven years we've had labs offering expanded T cell or lymphocyte subsets. But these are still populations of different types of cells and they show us numbers, they don't show us function. And we have other labs that will show us cytokine levels. All of these are taken, as you said, rob, from a blood sample, separate and removed from the moment-to-moment influence of local environmental signals and descending regulation from brainstem and let's say, the orbital frontal cortex and the insular cortex. But on top of that they're an amalgamation of all the different compartments of the body right, and, for example, if you're working with, like an autistic kid with a gut problem, you would love to know what's happening immunologically in the gut, not just the cell populations but their activity levels. And if we're dealing with an adult, say with Hashimoto's, we're trying to understand the immune system. We pull a blood sample and it doesn't show kind of a classic Th1 dominance that we tend to expect. And it doesn't show kind of a classic TH1 dominance that we tend to expect, like we can't really make any conclusions about the thyroid and the Hashimoto's process from a sample of blood that shows the amalgamation of all the immune processes that we're able to measure Right, and so the more that I learn about immunology and now bringing the brain piece in, the less satisfied I am with those as clinical tools. Now, that's I was going to say.
Speaker 1That's my opinion. I'd love to hear yours.
Immune Response and Lab Testing
Speaker 3This has been a discussion that Robert and I have been having for, you know, three to four years now, as I really dug into this deeper, my frustration with standardized labs that allow us to look at, you know, flow cytometry and look at, because again, we look at IL-6, for example. Il-6 has to really be in the acute state to probably see it elevated if we draw it. I mean, I know it's become popular since COVID and so many funk med practitioners are going around. Oh, you know, run this through a standard lab corp request. But I can tell you, I mean, if you do, you're probably not going to see it. I think that you know the thing that I've seen more reliable has been number one, the clinical presentation of the case. Okay, and looking at what you know tends to seem to be, you know, are the patients more Th2 dominant in their symptom presentation? Again, are we seeing that the history of atopic type of presentation? Are we seeing asthma? Are we seeing, you know, sinusitis, you know rhinitis, kind of things, utis? You know those things that tend to be more of those classic Th2 dominancies. You know, periodically, you know, again, if you're in maybe an acute state, you'll probably see the eosinophils elevate or you'll see the basophils elevate, okay, and they'll start getting upwards of 4%, 5%. I mean right now the research out there on mast cell testing. I mean people talk about it, I know there's a couple companies out there. On mass cell testing, I mean people talk about it and I know there's a couple of companies out there that are saying, oh, you know, they can look at mass cell activation and pinpoint it. Maybe they can and maybe it's a useful test. But I just go, based off the symptoms of what I perceive to be more of a mass cell type of activation and start down regulating Again.
Speaker 3Sometimes you'll see where you know, in the Th17 shift there'll be really, you know, acute Th17. So you'll see a high CRP that can indicate a Th17 shift. Or you'll see an elevated neutrophil level that's gone up in the upper 60s. You know low 70s where you can begin to say, okay, is this patient in a TH17-mediated immune response? Do you get, you know, maybe, their fibrin level? That's elevated, you know. Do you see an elevated ferritin level? That's elevated? You know again, those classic acute phase reactants.
Speaker 3But in a chronic case you may not see all that completely elevated. So I think for me may not see all of that completely elevated. So I think for me it's coming back to trying and then trying to catch the interval of it too. I think that's. The other big thing I've learned over time is that with lab testing, especially like with antibody testing, I like what seems to be what Vibrant's trying to do and even cyrix is trying to do, but to me I think the problem with those two is that they're cost prohibitive to be able to try to catch the contraction and expansion of the antibodies.
Speaker 1Yeah, and it's like it's a it's a snapshot in time and, like you said, like um, you know, these are very dynamic environments, right, very responsive to shifts and changes in those local environments, and it's like-.
Speaker 3And just like you brought up with the autoimmune patient with the Hashimoto's okay, at least with TPO antibodies right, that's a pretty, you know you can get that through a conventional lab and get a fairly inexpensive number and you can serial it. You can look at that over a period of a two week, 30 day, 60 day window, whatever that window is, and be able to look at it more. And then again the question has become like, if we're looking at it now more from the antibody glycation standpoint, is that you might have a low antibody level and it's out of range, but it's low, but yet it's a very aggressive response, okay, as opposed to the person that has a high antibody level and maybe they not having a lot of symptoms. So again back to this, this shifting of the the other, the TH17 system, into a more advanced, you know, a TH21 shift. You're going to get that response to where, you know now the antibodies are more, you know, more glycated and they're more sticky, and so now they're they may be more, you know, attacking that particular target tissue, and so so I think, you know, I think with labs I get frustrated, because I do, you know, dr Rob, and I get asked all the time like will you use this lab, will you use that lab?
Speaker 3And I'm like I don't know yet I'm not convinced that those labs are going to give me the clinical picture that a good case history is going to give me. And especially when working with you know some of these children that you know coming in right off the bat that at two, three years old they already shifted to a Th2 dominance and we can see it pretty quickly. And so we start modulating that down with some of the supplements we're using. And then, you know, as we're treating the brain more and we can get around that pretty quickly.
Clinical Frustrations With Lab Testing
Speaker 1Yeah, rob, going back to the idea of neurodevelopment and progressive stages, would you go so far as to say that, as the right brain comes online first, that it has a preferential influence over innate immunity, like neutrophils and monocytes and natural killer cells, for example? Or are we still in that place of we just don't know, like we have suspicions, but nothing's truly mapped out with high detail yet?
Speaker 2I think the way it works, steve, is that you know, from a bottom up perspective, you know, all of the again, seeds of what will become areas of the brain start in the brainstem and then they make their way up right and, as the brain is developing, as the child is developing, make their way up right and as the brain is developing, as the child is developing, and they make their way up into the brain. And we know that bottom-up development mostly favors right brain development, right? So I mean that's pretty clear. And so you know, we mapped all of this out this way and you know, I think, that so initially the brainstem, just like the vestibular, spinal, the reticulospinal, you know, some of these descending autonomic pathways, start in the brainstem and make their way down, and I think at the lower level we tend to have a bias towards being more sympathetic on both right and left. But then as we get this up and then as it starts to come down, if we get that, that's when the brain becomes more in control and regulates it and we get more. And just as you're describing, as we're describing this, you know, peter, saying that the immune system is so responsive. There's no way it's going to be that responsive purely through metabolic reactions. It can only be directed by the brain. Only the brain is going to move with that much speed right.
Speaker 2So again, and that's why, looking at these things, when we're looking at it outside of the brain, I've always been frustrated by lab work. I mean, I started I drew blood on every patient when I was first in practice over 30 years ago and I, from the very beginning, the labs didn't always seem to jive. And then I did. I've done as much food sensitivity testing as almost anybody and again, it never seemed to, always, like Peter would say, sometimes a level one would be more aggressive than a level five. And then even with the you know, finger prick antibody tests, I think they're a good guideline but they've never really jived. For me there's something missing, and Peter has this term that he would talk about that I think you learned from Sam what was that term, peter? Where it was like kind of there's this certain response happening when it doesn't really fit the way you think it's going to fit.
Speaker 3I'm going to try to remember now what I termed it.
Speaker 2What I'm talking about. It's like you said, there was this, I don't know, some sort of it's like this anomalous effect, and now there's a name for it, right, when? Okay, when the blood work isn't looking the way we look and the response isn't the way we expect it to respond.
Speaker 2So it falls onto this this name um and I said to peter from the beginning, I think that gap, that we've made this name up, is actually the brain and the nervous system, that you're right.
Speaker 2When it doesn't work the way, you don't think, and it's the same thing in the brain, you know, when people argue about the whole, is there the right brain, left brain? Um, because we don't see it on a qeg that way or whatever, I don't. Same thing in most of the imaging that we do, even in highest level research, it doesn't have the sensitivity to pick up some of these subtle little differences in brain activity that actually translate into big differences in behavior. And that's why we have to look at the behavior of the individual. We have to look at it, knowing what research has told us about right and left brain, and then it fits. Same thing with the immune system. We have to look at the behavior, the sickness behavior or the lack of sickness behavior. Kids with autism they don't get sick and even when they are sick, even when they have raging infections, they don't act like they're sick.
Speaker 1How do you explain that? And then, like I said, when they do get know it.
Speaker 2They don't know it. Yeah, yeah, right, how do you explain that? And then, like I said, when they do get sick, they may actually speak better. So you know, you have to be able to explain all of that and I, and I think that the lab testing and even brain testing at this point is not at that sensitivity, but that just because we can't measure it doesn't mean it doesn't exist, that uh, yeah, and the rob's point too.
Speaker 3I you know, one of the things I think the frustration with labs too, is that are they making their labs even too sensitive, right To where you know that they are wanting you to use their services, so much that are they narrowing in their sensitivity a little bit more? So I think for me, I think we're trying to put together an immunological labs of what we can hold our hand on the most okay and say, all right, hey, this is, we feel very you know, we run a vitamin D.
Speaker 3Okay, we can, you know we can put a lot of stock in that okay, if we can run like a CRP number, I think there's, you know, some real stability in that Okay.
Speaker 3So I think, where you're trying to find stability markers, but you know, I've run, you know panels where I've done TNB, lymphocyte, natural killer cell panels through Quest or LabCorp and didn't come out to match the presentation that I thought was going to happen, and you know, and then you go over here and you might run, you know what Cyrix has developed with their cytokine panel and the same thing.
Exploring Insular Cortex Function and Cases
Speaker 3It just doesn't seem to match. So I think for me I'm always trying to look at the clinical picture of the case and the symptomatology and then do the best that I can with some labs that I think are not too overexpensive, that we can measure and then try to get a serial pattern of that relationship. And I think for me, and what I've taught in Robert's course over the last three to four years, is that you know, just just doing a simple CBC because it's so simple to reproduce, Okay, and kind of see the trends and you can, and you can see just the, the trends of the eosinophils, or you can see the trends of the neutrophils and and stuff, and then you know if you see a lymphocyte panel, that is a lymphocyte number that comes up, you know. All right, maybe I do need to run a TMB natural killer cell profile and see that. But I mean, I don't think we're trying to like tell families that they got to run all these sophisticated labs to get that.
Speaker 1I mean, that's not where we're at right now we're just unsatisfied, yeah, and I would agree, I would agree more often than not, like a lymphocyte subset panel doesn't match my understanding of the clinical problem, and maybe the problem is with my understanding. But I've also found an issue with you know. Okay, so I have this pattern of whatever dominance or deficiency, and you know, here's a set of recommended supplements to change that. And I have not, I have not often see that change within what I consider to be a reasonable period of time, even though I might see clinical progress. Right, and so that's for me. That's when I started to go okay, really, where does this, where does this fit in my bag of tricks? And so I de-emphasized all of those things.
Speaker 3And I think it's true. I think there's an element of you know, one I always look at, you know, one of the things I've talked to Rob about is that you know, sometimes, you know, using just only a couple products might be giving us a chance to go vertical and be able to push the physiology enough. And then at the other times, also the idea of you know how underdeveloped is the brain, and even in adults adults I mean adults obviously can have these dramatic hemispherical balances and and and again. If you feel confident that, hey, your clinical plan is, from a metabolic or neuro-emological level, solid on the emological side of things, then probably the other equation of it is the neuro side of it and we haven't dug deep enough into looking at retaining primitive reflexes on these adults under development of these systems, these early systems of the brain that still are impacting the way their psychoneuroimmunology is working and their endocrinology.
Speaker 1Do you guys have any time limits or do you want to keep going?
Speaker 2I got another call at 630 my time, so I only have about another 20 minutes.
Speaker 1So, as always, I have more questions. Yeah, I got a few more minutes, and then I got to run Okay.
Speaker 1So are you guys okay to go? Because here's what I would like to do. I'd like to dive into the insular cortex. I'd like to talk to you guys about its functional organization, its network connections, how you might assess it, how you access it to change its behavior and its function, and then maybe talk about some cases that you guys have done. And you know, obviously that's a much longer conversation than just 20 minutes. So are you guys okay with scheduling another one? Awesome yeah, that's awesome yeah.
Speaker 2That's awesome yeah.
Speaker 1So I appreciate it, you guys. You are both a wealth of knowledge and the whole point of Functional the Funk Med Nation is to share, learn, grow and be inspired, and you guys are fitting the bill, so I appreciate your time.