 This is the nicest stage I have ever been on. I'm a grad student, we don't get nice things. They actually have a mic on my face, I don't even know what that's about. Psychoneuroimmunologist is what he was trying to grab, but I'll forgive you Ashkan. So I'm here to talk about float and the immune system. I'll give you a little bit more about that soon, but you know when I first got into this project I was really curious about what the community thought of float and the immune system. And so I went to the place where you can find, you know, it's the most trusted resource of personal opinion, the internet. And so I went on the internet and I was like, okay, what are people saying about float and the immune system? You know, so on one hand it's the immune function is enhanced by floatation, okay, so it does something good, right? And then on the other hand, there's, by reducing chronic inflammation, floatation therapy helps patients live longer, healthier lives. So here we're talking about reducing inflammation, but then we've got through the use of floatation tanks a person can actually strengthen his or her immune system. So then we've got strengthen again, and then I've got my personal favorite, floatation provides a place for you and your inflammation to calm the heck down. So what gives, right? You know, we have all of these mixed attitudes about what float does for inflammation. And I think the bigger question is why does it matter? You know, many of us are familiar with the idea that inflammation is involved in illness, and we're also probably familiar with the idea that inflammation is involved with injury and recovery. But I'm here to talk about how inflammation is also involved with mental health. And so this creates this big, really interesting question of how can float play a role in these three things? And the interesting thing about this is that it's a very complicated issue, and understanding the interplay of the immune system and stress and relaxation is what I want to talk to you today about. And you might be asking, well, what does this guy know, right? He doesn't have a PhD yet. Why am I a good person to be telling you this? Let me tell you a bit about myself. Those are my space sunglasses. If you've met me so far, you've probably seen me wearing them. I have an undergraduate degree from Thomas Jefferson University in Philadelphia. My degree was in biotechnology with a focus on genetics and cellular and molecular biology as well as pharmacology. So I studied drugs and cells and people and how to put it all together in biotech. I have a master's degree from NYU in neuroscience where I studied the primate visual system. I worked with monkeys, and I learned how all the different neural circuits that go with how we see things kind of put together a big picture. And then currently, I'm at the University of Colorado at Boulder where I'm working on a dual PhD in neuroscience and clinical psychology. I have the privilege of getting to be a therapist while I also do research that really connects our understanding of mental health with the treatments that we're giving people. And so last summer, when I met Justin for the first time and got to float in his tank in Tulsa and really experience how transformative flotation can be, I realized that this was such a perfect merger of all of my interests and my background because I could look at how flotation can affect mental health, but I could also take a look inside the body and the mind to understand how that's actually being affected on a cellular and molecular level. And I want to talk to you about that today. So just to kind of give you an idea of where we're going, I'm going to start with a brief introduction to cell and molecular biology. Now, don't get scared. I know it's super complicated, but in order to really understand how unique and amazing some of the results I'm going to present to you later, I want to make sure we're all kind of on the same page. And so after we get through that, I'm going to talk about the evolution of the adaptive immune system. So so often when we hear words associated with the immune system, and inflammation sounds bad, and boosting the immune system sounds good, but inflammation and the immune system are really one and the same. And really understanding how it evolved and how it evolved to work properly. And then taking that and looking at its context in modern times is how we're going to understand this bigger picture. And then I'm going to end with flotation in the immune system and anxiety. And this I'm super excited about. I literally just finished this analysis a week ago. So you're going to be looking at information that is hot off the presses. No one besides my advisors has seen this yet. So you're in for a treat by the end of this presentation. So let's start with our cellular and molecular biology boot camp. So to start, we've got our little person here, look inside her body. And something that you may know and may have heard of is that the cell is the smallest unit of life that there is, right? So if you divide all life down, the smallest thing is going to be the cell. And our bodies are made up of lots and lots and lots of different types of cells. And for the purpose of this presentation, the one thing I want you to know is that some of these cells stay in one place, like a skin cell. Your skin cells don't really move around, they just stay where they are. Whereas other cells in the body, like your red blood cells, move around. And they go to where they need to go in order to deliver nutrients or share information. And it's that sharing of information that is really critical for understanding the immune system, specifically what we're looking at today. So I want to talk about how cells communicate with each other. One way that they communicate with each other is through mechanical communication. So movement. If you get touched, your skin cells are going to move. That movement is going to activate neurons. And those neurons are going to send messages. So that's one way cells can communicate. Another way is through electricity. A really good example of this is your cardiac muscle cells. They actually send electrical impulse from cell to cell to cell to make sure that your heart is beating in time and with the right rhythm. But finally, and the most important for this presentation today, is there are chemical signals. And so let's zoom in on that a little bit. So some cells, like this red cell here, release chemical messengers, just tiny little chemicals. And those chemicals can then travel either across a short distance, like in this picture, or across long distances throughout your entire body. And then those chemical messengers relay messages to other cells and they change their function. And they do different things. And in the immune system, those chemical messengers are known as cytokines. And that's a word I'm going to be using a lot, because cytokines are how we measure immune function when we're looking at it on a molecular level. So for the purposes of this presentation, I'm going to be talking about things on three different levels. The first is going to be molecular, talking about those chemical messengers. And anytime you see a little cartoon face, because I love cartoons, you're going to be talking about a chemical messenger. And it might be a cytokine, it might be something that has to do with stress, I'm going to be really explicit about what they are. But just remember, if you see a face or a little character like that, it's generally referring to something molecular, chemical messenger signal. We're also going to be talking on a cellular level. And I didn't make any of the cells into cartoons, they're just kind of blobs that look similar to this. So anytime you see something like that, we're going to be talking about cells. And then finally, we're going to be talking on a behavioral level. Like what's actually happening when these chemical messengers and cells are communicating? And for that, I have my little friend here, her name is Clara. She has followed me around for three years now. I use her and her friend, Randy. Randy doesn't show up in this presentation. But they're my little cartoon characters that help me to explain things when I'm giving talks. So in order to really understand the immune system, and in order to understand how it's adaptive and how it evolved, because understanding that will then give us the idea of how it can go wrong, we're going to have to go way back in time. We're going to have to go back in human history and we're going to be using cableman Clara. In order to talk about the immune system and how it evolved, I'm going to be talking about three different stories. There is escaped Clara, there is injury Clara, and there is survival Clara. Each of these is going to be a different vignette in how the immune system evolved to be adaptive, to actually help us survive. And then I'm going to take pieces of that and talk about how it's gone wrong in modern society. So let's start out with escaped Clara. So Clara is a hunter-gatherer and she likes picking berries and weaving baskets and I don't know, whatever they did 20,000 years ago. And so one day she's out picking berries and suddenly a saber-two tiger appears. And she is freaking out because she doesn't want to get attacked, he's stalking her, she doesn't quite know what to do. And so right now, before anything happens, very specific system that has to do with stress in Clara's body is being activated. That system is known as the sympathetic nervous system, but you're probably more familiar with it as the fight-or-flight system. And so I want to kind of tease apart these stress systems because they're really important to understanding the immune system. So the fight-or-flight system starts when signals from your brain travel down through your body and synapse on your adrenal glands and they release specific chemicals that you're probably familiar with. One is epinephrine, also known as adrenaline, and the other is norepinephrine, or noradrenaline. And now these molecules then spread through your bloodstream and communicate with all parts of your body and they do a few very specific things that allow us to either fight or flee. That includes things like pupil dilation so that you can get more light into your eyes so you can see what's going on. Increased lung capacity so that you can actually move and get running. An increased heart rate to get your blood pumping so that it goes everywhere through your body that it needs to be. And finally, increased blood glucose. And glucose is your body's main energy source and so that glucose can travel throughout your body and give you the energy that you need to move. And so what does this do for Clara? Well, in this case, it allows her to drop her berries and run away, which is great, right? So the stress system worked. But there's something else that the sympathetic nervous system does that facilitates preparation for things that might happen because something, this might have gone differently. Clara could have actually gotten attacked and she could have gotten scratched or broken a bone or maybe while she's escaping, she trips and scrapes her knee and the body needs to be ready to tackle those types of problems. And so the sympathetic nervous system has evolved a really efficient way of turning the immune system on to prepare for possible injury or sickness in response to this stressful situation. And I wanna talk a little bit about specifically what that means. So one way that it does it is that the sympathetic nervous system, the neurons that activate that system not only tell the adrenals to release adrenaline, they also communicate with different immune organs in our body like the thymus and the spleen to help to mobilize our immune systems and get us ready. But I'd like to talk about one other cell that is gonna play a key role in this presentation and it's something known as a macrophage. Now macrophages are all over your body. They are kind of the resident gatekeepers and soldiers of the immune system. And if you were to have a cut or something were to happen in a local spot, that would activate macrophages just in that location. And those macrophages would then release signals and they would bring other immune cells and other immune molecules to that location to help you to heal. But something different is happening with the sympathetic nervous system. With that, we're dealing with activation of your immune system on a full body level. And what does that mean exactly? Well, I wanna take a look at this specifically on a molecular and cellular level because it's gonna be important for understanding the results that we found later on. So what happens is that epinephrine or adrenaline can actually activate a macrophage. And that leads to the release of several cytokines that are really crucial for understanding for the immune system to function. Two that I'll be talking about today are IL-1-beta and IL-12. And we're gonna let IL-1-beta rest for a minute. I'm gonna come back to him later. But IL-12 basically works back and reactivates the immune system. So if epinephrine is activating one macrophage, that macrophage releases IL-12 and that IL-12 then is able to activate tons of other macrophages in the area through talking to some other cells which is a little more complicated than you need to know right now. But basically, IL-12 helps to amplify your immune response. Now I'd like to kind of move away from that and talk about how we regulate this. So there's another stress system in our body that you are probably familiar with based off of its end product. And that's known as the HPA axis. And HPA stands for the hypothalamus which communicates with the pituitary which then communicate with the adrenals. And the byproduct of this stress system is cortisol. Cortisol is probably something that you've heard of. Now what's interesting about this is that it's on a time delay. The sympathetic nervous system or our fight or flight system happens almost immediately. Signals from our brain go down to our adrenals, suddenly adrenaline's released, that's why it's so fast. The HPA axis takes a while because you have to get signals from the hypothalamus to the pituitary to the adrenals. They're not direct, it goes through the bloodstream, and it kind of swoops in a little later. And the reason for this is because it's more for long-term stress adaptation. If our fight or flight sympathetic nervous system is more about doing something right away, the HPA axis with cortisol is about preparing you to survive for the long haul. It also frees up energy but in a bit of a different way than sympathetic nervous system does. And something that's really important for this presentation is that it regulates the immune system. Cortisol is one of the most potent anti-inflammatory molecules in our body. In fact, it's so potent that we use it as treatment for inflammation. Glucocorticoids, cortisol injections, different things that help to reduce localized inflammation. And it does this in two specific ways. So let's take a look back at our macrophage that's activated, releasing the IL-1 beta and the IL-12. And in this case, the cortisol can act directly on the macrophage and completely shut it off. But not only that, there's a second way that it can do this and that's through a mediator. Cortisol can act on an immune cell known as the T cell that T cell then releases another key player, IL-10, and then IL-10 can also turn macrophages off. And those three, oh, let's go back, those three side of kinds are the ones that we're going to be talking about in my results today and I'll be referring back to them. Okay, so cortisol, systemically, can basically turn the immune system off. And that's what we want, right? So in the case of our story, Claire gets startled, almost attacked, she escapes and because she escapes, she doesn't really need an immune response anymore. And so later on, the cortisol comes in and it just shuts that all down. So just to give a brief overview, we've got Clara, we've got the saber-toothed tiger, we've got activation of the sympathetic nervous system in the release of adrenaline and noradrenaline. Then this goes on to activate the fight or flight response and Claire is able to escape. And because of that, her immune system gets turned off by cortisol which comes down and comes in a little bit later. And this interplays incredibly adaptive because we want something that's going to be able to get us ready, but then to shut off if we don't need it. So let's talk about another way that the immune system is adaptive for survival. And that is in the story of our second Clara, injury Clara. So in this case, we've got Clara collecting berries again and again, saber-toothed tiger comes around. But this time, Claire's not doing so well. She gets attacked, she survives and manages to escape, but she's dealing with some severe injury and trauma. And so how does the body respond when there's an actual need for the immune system to work? And I would love to talk about this individually if you find me later and missed what I was saying at some point. I could talk about this for hours. So anyway, so we've got what we talked about where the immune system starts off. We've got the adrenaline and noradrenaline turning on the immune system through the macrophages. But then we have this whole thing with the cortisol turning it off. Now, this isn't the whole story because what's interesting is that cortisol at high concentrations is what turns off the immune system. But cortisol in low concentrations actually facilitates the immune system. So in the very early stages of an HPA access response, when cortisol is just getting released and there isn't a lot in your body, it's actually allowing the immune system to do its job. And it isn't until cortisol increases that it starts to turn it off. Now, this window of time provides an opportunity for the immune system to catch hold and to mount a response that is necessary for survival. And, oh yeah, and that allows it to then extend the system or the response for as long as necessary. And what ends up happening, I like to think of as a tug of war between cortisol and the immune system. So basically what happens is that in these early stages, cortisol in low concentrations allows for the immune system to start to increase. But then the body tries to compensate and it increases the cortisol and then the immune system starts to go down. But because you're injured and sick, the immune system comes back and keeps pulling and it keeps going until we reach a bit of an equilibrium. And that equilibrium stays as long as we have an active immune response that is necessitating the need for healing or for fighting infection. And so the question is how exactly does this happen? Oh, now that's another slide. This is what happens next, right? So we talked about how the immune system got shut off before, but what happens when your immune system is allowed to continue and you have this immune response that's being built up? So for this, we're gonna look at IO1 beta. And IO1 beta is kind of like this master controller for your immune system, especially for broad spectrum inflammation that's throughout the entire body. And it does this in a couple very specific ways by the encouragement and creation of something that the literature calls sickness syndrome. The sickness syndrome is a collection of behaviors and physiological responses that facilitate healing. So let's take a look at that. We've got IO1 beta. One of the things that it does is that it activates the hypothalamus to basically reset your internal temperature gauge and produce a fever. Additionally, IO1 beta can communicate through the vagus nerve, which is a nerve that's kind of inside of your body, directly to the brain to help alter other certain behaviors that will help facilitate this. Another one, and this is one of the most interesting mechanisms that I know of, is that it can actually travel into the brain and affect neurons. So that little inset there is looking at neurons, right inside the brain, and we're looking at a specific type of neurotransmitter here. You might know it. It's called serotonin. Serotonin is involved with mood. It's also involved with a lot of other things. And what IO1 beta does is it actually decreases the amount of serotonin that's in your brain. This is the exact opposite of what an SSRI does. So most antidepressant medication, SSRI stands for selective serotonin reuptake inhibitor, actually increases the amount of serotonin at these synapses. When you're sick, your immune system does the exact opposite, and it actually reduces the amount of serotonin that is in your brain. And so what does that actually do functionally? Well, there are a couple of different symptoms that are associated with this change. One, it increases fatigue, increases pain sensitivity, decreases appetite, leads to social withdrawal, and can lead to an increase in anxiety. Do those symptoms look familiar to anyone? Looks just like depression, right? We're gonna come back to that. So Clara is able to find her clan and they help her heal. She's doing a lot better. And so now we go back to our tug of war and because she's all healed up, her immune system has gone down. And cortisol wins out and the immune system gets shut down. There we go. So just to give a brief summary of this, this is what we looked at before. I'm just gonna simplify it because it would get really confusing if I added everything in to this. Basically saying that cortisol kind of shuts everything down. So what happens next though is if you get sick, it leads to that tug of war that leaves the immune system working, then leads to sickness syndrome, then when healing occurs, it comes in and the body pays attention to the cortisol system again and it all shuts down. Another way that the immune system and our stress systems evolve to interact for an adaptive process. Now I'd like to talk about one more story and that is survival Clara. This is a case when we need to ignore what our stress system is telling us. So in this story, Clara again gets attacked and again she gets hurt, but this time she's stalked by the saber tooth tiger and she stalked for a very long time so much that she gets completely lost and she is forced to wander the wilderness. Now in this case, Clara is going through severe trauma. She's starving, she's dehydrated, but she also probably has gangrene and is sick and so her cortisol rates are through the roof. But if she ignored that cortisol, or if she paid attention to that cortisol signal and shut down her immune system, she wouldn't have that long to live. So the body has evolved an amazing mechanism for actually disregarding cortisol in cases of extended extreme stress. Basically, like we talked about before, epinephrine activates the macrophage, cortisol comes in, turns it off and you ignore that signal. However, in some cases, during extreme stress, our cells, including the macrophage, adapt and start ignoring that cortisol signal and they stay on for extended periods of time. And this is in order to facilitate healing even if we're under extreme amounts of stress. Basically, leaving that system on. So again, let's do a really quick summary. We've got, this is what we were looking at before, but instead of her healing, we've got her traveling around and this leads to an ignoring of the cortisol signal and keeping that inflammatory system on. So these are our three historical cable women, Clara's, but what does that mean for us in modern times? How does this affect the way that we interact with stress and immune system today? Well, we don't really have sabertooth tigers around in modern times, at least not yet. I feel like Elon Musk is probably working on that somewhere. But these modern day stressors include things like negative life events, interpersonal stress or situational anxiety like public speaking. And these different events can all act in the same way as that sabertooth tiger stress did before and act to turn on the immune system. However, in most people cortisol then comes in and is able to shut the system back down. And so that's how being in a stressful life situation is still kind of controlled in a way that's adaptive. But what about when it's disrupted? And what can that look like? So the really interesting thing about this is that we see these same stressors, but for some people instead of them being temporary stressors, we interpret them in the same way as we would injured Clara. We feel like we're actually in a long-term situation of fight or flight. And in that extended way, we then enter into that push-pull between cortisol and the immune system. And then that activates all of those sickness syndrome symptoms that we were talking about before. But in modern times, that actually does look like depression. And in this way, this extended stress can lead to depression and mental health issues. However, even in this case, eventually cortisol will win out and you'll go back to normal or go back to a typical non-depressed existence. But there's one other piece here that is really crucial. And that's the fact that early childhood adversity, early life extended stress can actually change the way that we respond to stress in adulthood. In fact, early life childhood adversity can act just like that wandering Clara in the wilderness. When you expose a child to extreme stress that includes poverty or abuse, you're basically rewriting their body so that it stops paying attention to the cortisol signal that is there to shut down the immune system. And so what happens from that is you get these constantly activated immune cells which then leave the inflammation completely on. And that leads to a perpetual state of chronic inflammation in individuals and children who are dealing with this. And the really scary part about this is that children who are exposed to early life stress and develop a, desensitize themselves to cortisol, grow into adults who have the same issues. And this problem then leads to chronic low grade inflammation in adulthood which can then not only lead to mental health problems but also physiological health problems like auto-immunity or heart disease. So let's just do a quick summary. We've got modern day Clara and she has a negative life event. Looks like she's gotten half on a test. This activates her sympathetic nervous system which then leads to a fight or flight response because she has nowhere to go, might just lead to rumination, kind of thinking about things. And in some cases, and this will lead to the immune response but the HP axis will turn it off. However, if Clara interprets this F as something that's life altering and really, really horrible for her, this actually leaves the immune system on in that push, pull, tug of war between cortisol and the immune system and leads to sickness syndrome or depression. But even that may eventually improve allowing for cortisol to shut it off. However, in cases of extreme stress in childhood, this can lead to ignoring of that cortisol signal, leading to constant low-grade inflammation which then can lead to health problems later in life. So just to briefly summarize, the immune system is activated in response to modern day stressors. Disruption of the immune system in response to stress may cause anxiety and depression in some people and early life adversity can lead to a lifetime disruption of the immune system. But in my last few minutes, because I'm a little over time, I wanna talk about the role of float and the immune system because that is what can be really transformative, right? That is what we're looking to find is whether these types of relaxations through flotation can actually help us to regulate our immune system in a way that's more adaptive. I've been working with Justin at the Laureate Institute where we're looking to find novel therapeutics for psychiatric illnesses. Saw this picture already and I'm just gonna breeze through this. This is our study. Justin talked about this already. This is the basic idea and we had the blood draws pre and post. This is the study that he showed before and again, this was the full thing. People either floated or they watched Planet Earth and then a week later, they did the opposite. So we have all of this data to look at. So now I'm gonna show you a couple graphs and I'm gonna walk you through them briefly just so you're not scared of them because they're a little complicated. So this is the basic idea. We're gonna be looking at IO1 beta, IO12 and IO10. Along the middle here on this up and down axis, above it is when there's an increase in concentration of a cytokine and below it is going to be when there's a decrease in a concentration of a cytokine. And our conditions, the earth condition is green, the pool condition, the flow condition is blue. Oh and the lines are going to be basically the relationship, the dots are gonna be the individual people and then at the bottom on that horizontal axis is going to be a self-report measure that's related to anxiety. So something about anxiety that we measured in people. So let's take a look at the first one. This is IO1 beta and you can see a basic interpretation of what we're looking at right there on the side. And what we found is that people who are more sensitive to anxiety, people who are more likely to interpret different types of physical stimuli as leading to anxiety. The more sensitive they were, the more they showed a reduction in IO1 beta in response to float. But not the earth condition. Basically, the more of a probability you have to being anxious, the more your immune system can benefit from this condition. And that's just staggering. We also have some results with IL-12. Similar, but this has to do with the amount of anxiety that people experienced in the previous week. Again, the more anxiety that they experienced in their week previously, the more benefit they had by lowering these inflammatory cytokines in response to float, but not earth. And finally, we've got something in a bit of the opposite direction. If you remember when I mentioned IL-10, it is an anti-inflammatory cytokine. It basically helps to reduce inflammation. And what we showed was that for individuals in the float condition who increased in feelings of relaxation in response to float, the more relaxed they felt, the more IL-10 was being produced in their body. They're basically having an anti-inflammatory response that is proportional to the amount of relaxation that they're feeling. And these results have never been seen anywhere before. They're amazing. I'm super excited to start working more on this. We have a lot more work to do. Some of the things we need to do in the future include more float sessions, which is that grant that Justin was talking about earlier that I'm super excited about will be able to see how the immune system changes in response to multiple float sessions. We also need to get more people. You know, these immune responses are small and it takes a large group of people to really understand what we're looking at. And the more people we can get involved to better. And finally, we want more information, asking people more questions, getting more data, really finding other ways that this can all go together. And through that, we'll be able to really make a dent in this and figure out the role that float can play in helping us to regulate our own immune systems. Thank you.