#33 Why We Breathe? with Dr. Jack Feldman

Introduction Of Podcast

All of us know breathing is important for living beings, especially humans to survive. Ever wondered what led us to this process? What the origins of breathing are? In this episode, Dr. Jack Feldman, a renowned neurobiologist, answers all these questions. We also discuss the role of breathing and how can breathing patterns can have a say in our longevity. You’d not want to miss this.

Timestamps

  • (00:00 – 01:51) – Introduction
  • (02:12 – 04:52) – Role Of Breathing In Human Evolution
  • (04:59 – 14:07) – The Mechanism Of Diaphragm
  • (17:11 – 33:11) – Affects Of Breathing Patterns
  • (33:56 – 43:03) – What Is Sighing & Can It Be A Biomarker?
  • (46:35 – 49:46) – Dr. Feldman’s Choice Of Breathing Techniques

Key Takeaways – Transcripts

Intro (Mohit): Today’s episode is special. In fact, today’s episode might just take your breath away, quite literally. Well, because we are joined by one of the world’s leading neuroscientists and neurobiologists with decades of research into breathwork, Dr. Jack Feldman. Dr. Feldman has done distinguished research in the mechanism of breathing and sighing. He’s a professor at the UCLA and has published over 150 peer reviewed papers in the scientific journals. He is an extremely coveted and well regarded scientist in this space. On this episode, we start by talking about the basic: why do we fundamentally breathe and what’s the role of breathing in human evolution. We dial it back because it’s critical to understand where it all began and how it began. We then segue into understanding the mechanics of diaphragm. The conventional norm is to believe that all of the activity during breathing actually happens in the lungs. But then you’ll be surprised to know how big a role our diaphragm actually plays in our breathing. Dr. Feldman also talks about how he discovered the pre-Botzinger complex. A fun fact not many know, but this phenomenon was named after a bottle of Botzinger wine that was being served during a dinner in 1978. The experiments that led to the discovery of the pre-Botzinger complex are much more interesting. You wouldn’t want to miss this. We then discuss the role of breathing and stress regulation and especially the impact that sighing can have on our health. We discuss if and whether sighs can be a biomarker for people to track. And you’d be blown away with some of the insights that Dr. Feldman shares on this segment. We can close the episode by finding out Dr. Feldman’s choice of breathing techniques that can improve your life right away. Strap your seat-belts for this one. Let’s get into it.

Question (Mohit): Hello, Dr. Feldman. It’s such a pleasure to have you here. And good morning to you. Well, I would love to begin with this amazing question that might sound very, very basic, but what role does and I think we will talk about a lot of amazing work that you have done in this space. But I would love to begin with the fact that the question that what role does breathing have in the evolution of mammals and humans specifically? And maybe we can just begin there.

Answer (Jack): It’s a pretty big question. We’ll need a couple of hours to really address it. Let me see if I can be terse. So when vertebrates came out of the water, we were predominantly expiratory breathers because we did not have the muscles to generate powerful inspiration. So if you look at amphibians and reptiles, they’re predominantly expiratory breathers, which means that they contract their chest with active muscle activity and then they relax. And this works well for amphibians, but it produces severe limits in how much air they can exchange through their mouth and nose because the chest wall is not mechanically very efficient. And somewhere along the line of evolution of invertebrates and there are lots of people who have ideas about what happened. The diaphragm developed and the diaphragm is a very special muscle. It’s entirely internal. It separates the lungs from the sub-diaphragmtic viscera  and it has some amazing properties, but one of which it’s extremely efficient for expanding the lungs and that is producing inspiratory effort. So there’s a switch in vertebrates and mammals to becoming inspiratory breathers. So we became inspiratory breathers where we actively inspire and arrest, we passively expire. The advantage that had is that it allowed us to evolve lungs which had much more surface area in a given volume, which means there was a greater opportunity for gas exchange. And there’s a lot of all sorts of things to happen. We could become warm blooded and in particular, as we get higher and higher above on the evolutionary scale, we can develop big brains, which are extremely demanding of oxygen, and oxygen be continuously delivered. If you go more in a few minutes without the breathing, it potentially could cause irreversible damage to the brain. So here we are. We’re mammals that are very special. We have this very powerful diaphragm and we’re primarily inspiratory breathers who exhale passively. Now, when we need to increase our ventilation, we begin to engage our expiratory muscles so we can move more air. So I think that’s sort of a 25 words or less summary about where we stand as humans.

Question (Mohit): That’s amazing. And there are so many interesting segues that we can take here, but I would like to take, and you mentioned the diaphragm quite a few times. I think it’s really interesting how understated the diaphragm muscle is. It’s not talked as much about, but I’m really interested as a segue largely around the area that the diaphragm area, the area that separates the viscera, the entire area and what really happens in that, essentially, right? So tell us a little bit about more about where the diaphragm actually works, like what sort of leads to the contraction and sort of like the overall mechanism of breathing, like what is the in some ways the motor function or the logic behind diaphragm, because as you mentioned, this happened because of result of evolution.

Is the primary role just breathing for diaphragm or is there something else there?

Answer (Jack): There’s a lot of things to unpack there. So let me first start with the mechanics of the diaphragm. The diaphragm is a skeletal muscle, which means that it doesn’t have any activity on its own. This is in comparison to cardiac muscle. Cardiac muscle, which drives the heart rhythmically, doesn’t need any inputs in order to work. Whereas our skeletal muscle, including all the muscles, like in our limbs, requires input from the nervous system in order to contract. So if I want to flex my elbow, I need to contract my biceps. To do that, I have to send a signal from my cortex down to my spinal cord. And then there’s a special population of neurons called motor neurons, which specifically innovate the muscle of the bicep. And so when I activate them, the diaphragm contracts. And depending on the resistance, my elbow will flex. So the diaphragm is a similar muscle in that the nervous system constantly has to be sending out a periodic signal when we want to inspire. And when we inspire, the diaphragm is sort of an upward facing dome if you’re sitting up or standing up. And when it becomes activated through the nervous system, it pulls down a little bit, maybe about a centimeter, a centimeter and a half. And because of the way the lung is configured inside the rib cage, the pulling down the diaphragm and typically a modest or expansion of the ribcage that increases that volume in which the lung is sitting and that forces the lung to expand. And if the airways are patent, there’s no obstruction. Air is going to flow in through the nose and mouth, down the trachea, down to all the branching, ultimately getting to a place in the lung called the alveoli, which is where the rubber meets the road, as we would say. And the air is able to go, or the oxygen is able to go from inside the lung into the blood. And the carbon dioxide, which is produced by metabolism, is able to go from the blood into the lung, which, when we expire, we’re able to expel the carbon dioxide. So that’s how we take the air in and out. Now, also important inspiration are muscles of the ribcage. And there are really two types. There are the external intercostals, which are sort of on the outside. And when they contract, the ribcage rotates up and out, which is an inspiratory effort. And then there are the internal intercostals, which are pushing the ribcage down and in, which are expiratory. Now, I should make sure I emphasize that when the skeletal muscles are not being actively contracted, they relax. So with the diaphragm, when I inspire, I send a signal. The diaphragm actively contracts. When I stop inspiration, I don’t need to send a signal. All I have to do is remove that signal and the diaphragm relaxes back. So breathing, normal breathing, is a little bit like a pulling on a spring. The diaphragm contracts, the external picastos contract. The lung, which is sort of a rubbery membrane, expands. And then at the end of inspiration, I stop and the lung being sort of this elastic tissue is going to go back to its normal state as well as the inspiratory muscles. So that’s how the peripheral mechanics sort of work. What has interested me and my colleagues is to try and understand how that signal is being sent out there. So for the diaphragm, there’s a population of these specialized motor neurons which innovate the diaphragm. They’re called phrenic motor neurons and they’re located in the upper part of the spinal cord. But these motor neurons themselves are passive recipients of signals, so they themselves are not generating the rhythm. The rhythm that they receive is coming from higher up, from a region just above the spinal cord called the brain stem. And the signal comes from the brain stem, and it’s periodic. There’s activity silence. Activity silence. In the late 1980s, we sort of identified an area which has been of interest probably for thousands of years. That is, where is breathing coming from? Where is the engine for breathing? And this had been speculated in Eastern cultures, in Western cultures, in the post Renaissance, beginnings of neuroscience. They identified a region in the brain stem which appeared to be critical for breathing, but didn’t go much further than basically saying it’s in the brain stem, which is sort of back here, just above the neck area in the back. And we were fortunate enough with Jeffrey Smith to do experiments where we were able to isolate a region that we hypothesized was generating the rhythm. It did not have a name in any of the atlases, so we took the liberty to name it and we named it the pre-Botzinger Complex. And then we were off to try and test this hypothesis. And I think it took about ten years before it was generally accepted that, in fact, this is the principal engine for breathing. But you have to remember that breathing is not just the engine, any more than the car is just the engine to get a car to move. There’s all these other things that need to be coordinated. So this is driving the rhythm, and if somehow it gets damaged, you lose the ability to generate the rhythm. Now, there are other ways we can drive the rhythm of breathing. We can volitiously breathe, and so we can do that when we hold our breath, we can emotionally breathe, which is quite distinct, actually, from the volitional breathing. So when we cry, when we laugh, that’s coming from a different part of the brain. So this begins to speak to the issue you raised about what the other things breathing involved in – speech, we’re able to talk to each other. If we’re non-human vertebrates, we use the movement of air for all sorts of communications. We have all sorts of reflexes that are important. We cough, we sneeze, we sigh. And those are very important to maintain the airways being clear. You get mucus in the airway, you want to cough it out, we need to sigh. In part, we have what we call physiological sighs, which are necessary to maintain the proper health of the lung. And I can explain that if you want me to go into that. And so there’s lots of things that breathing is important for, and I’m sure that well, I know there’s a lot of interest that’s been developed recently in trying to understand how changes in breathing can affect our emotional cognitive state. I mean, we’ve known about this for thousands of years going back to things in your part of the world, in your country and in practices like yoga, where changes in breathing practice have been well documented to have profoundly and mostly positive effects on emotional and cognitive state. What we have become interested in is to try and understand how this is happening. How by changing your breathing pattern, can you suddenly feel calmer? Can your cognitive function improve? And we can get a little bit into that if you want. So there’s a sort of a two way street here with breathing. Breathing is involved in all sorts of behaviors. The most fundamental one is blood gas regulation. That is oxygen, carbon dioxide. And because of carbon dioxide, it’s regulating the blood gasses. But that’s not the only thing we’re moving here for. We’re moving here for all sorts of other behaviors. And then there’s the flip side of it. That is how controlling breathing can affect various aspects of our behavior. 

(Mohit): Wow Architecturally, before, I think the point that you made around the impact on behavior speech, we can say essentially the movements and all those aspects of life Architecturally, what you defined was that there are oscillators essentially in some area of the brain, in this case the brain stem. You mentioned the pre-Botzinger area. And this is for inspiration, largely the inspiration side of the breathing. And then there is a spinal cord and then there is essentially in a simplistic way, potentially the lungs are connected to the spinal cord and then these instructions are carried out by the lungs. Now this has a downstream effect.

(Jack): Can I interrupt for a second? Because I think there’s a common misunderstanding that the nervous system is directly causing the lungs to expand or contract. It’s indirect. And the mechanics there and the physiology physical state actually have consequences. And for example, if you have a puncture of the ribcage, you get what’s called the pneumothorax. The lung could collapse. So the coupling there is rather complicated. But what’s being driven a skeletal muscles, not the diaphragm. The diaphragm is just like a passive balloon that’s being pulled apart and allowed to relax.

Question (Mohit):  Got it. So on that note, it’s sort of like connected ecosystem and in a way indirectly or directly driven by our physiological signals that might or might not drive this entire process. And what it reminds me is that when we study, let’s say hormonal pathways in the body, right, how these hormonal pathways are connected, it’s sort of like reminiscent not pretty much, obviously different part of science, but like how dopamine affects serotonin and essentially the downstream effects on other parts of the hormonal pathways as well. It sort of seems like that Ouroboros system, like one thing affects the other and one thing feeds into the other, philosophically speaking. But you also brought up like a very, very interesting point around how stress has a role to play or let’s say breathing has a role to play in terms of stress regulation and other aspects. You talked about Eastern philosophy and there’s a lot said growing up in India, there’s a lot of emphasis on breathing exercises. What I would see is that my parents would actually dedicate special section of their workouts or yoga, to actually breathing exercises. And we used to call it Pranayama. That was fascinating because for the longest time, for the first 30 years of my life, it didn’t make sense to explore what’s inside pranayama and just remember and do what’s being taught. But then the concepts that you mentioned, like there are Pranayamas that essentially are on the basis of breathing in air, but there are a lot of

them which specifically make you force breathe out. And I’m really interested in the ones that actually make people breathe out first because it seems unnatural. But then based on what you said, it also seems a lot logical. So have you explored some of those I’m sure you would have explored some of those breathing patterns around sort of like expiration and what sort of downstream effects does it have on the body?

Answer (Jack): Okay, so I have two points, I think, that can help address this. The first is that we originally thought when we identified the pre-Botzinger complex, that it was the sole source, not just for inspiration, but somehow for expiration, that you have like a single oscillator, like day and night comes from one oscillator that is the Earth turning around. And so we thought there was one oscillator. But in the early 2000s, we got data suggesting that there may be a second oscillator that’s primarily involved in generating expiratory movements. And what we did not fully appreciate was that at rest, expiration is passive. You inhale and you relax. And so when we did our experiments looking for places that may be involved with exploration, the regions that were involved in generating the passive expiration, there doesn’t seem to be any. What seems to be is that there’s a region involved in generating what we call active expiration. But in our experiments, we didn’t have situations where we had active expiration. But then in a way, we stumbled across this and we were able to follow up on it. And we did identify a second region which we’re now convinced is responsible for generating active expiration. So while we’re sitting here quietly talking, of course we’re using expiraroty airflow to speak. But for our basic breathing, our exploration is passive. But when we need to increase our ventilation, we have to turn on this active expiration. And it seems to be separate. Now, one interesting question being we’ve talked about evolution is why would it be separate? Well, if you go back to what I said about the evolution, invertebrates, the initial respiratory pattern was primarily expiratory. It was only later that mammals became inspiratory. And so the respiratory oscillator, we would suggest, persisted. And the inspiration oscillator developed and became dominant because it allowed for much more efficient breathing pattern, which lungs with much greater surface area. So now there’s clear evidence that there are two very distinct oscillators that in normal conditions are so tightly coupled we can’t really separate them. Now, as far as what kind of exercises or what kind of breathing patterns have, what kind of outcomes, I think we’re in the exploratory stage. I’ve read a lot about the different practices, breathing practices, and experimented with some of them myself. And I would say it seems quite evident that the different breathing patterns can have different outcomes. And your question is why? And I think this goes to a more general idea about how breathing is influencing all these higher functions. In the past 15 years or so, many colleagues have identified rhythms in the brain that are breathing related. So we’ve known for maybe 100 years, maybe a little bit less, that there are oscillations in the brain. That is, things that don’t seem to be tied to specific behavior, but activity waxes and wanes. And these typically range from a few times per second up to maybe 100 times per second. And they have different designations, typically with Greek letters of alpha, beta, delta and whatnot. And neuroscientists have been investigating and trying to understand what role these oscillations play. And two ideas that seem to have favor is one, it’s important in what’s called binding. We’re having this conversation here. You hear my voice, you see my lips move, you see my face. You don’t see this as three separate screens. You see this as one unified whole. And yet the sound is coming in through your ears. Anything related visually is coming through your eyes. So the question is, how does your brain put that all together? And when you look in detail at how the brain may be doing it, the timing of these signals is very important.In other words, if the signal is delayed a littlebit, it may not be coming from the same place. And so how does the brain make sure that we know that the input coming into different places is really coming from the same origin? So one thing that appears to do is to use these oscillations as sort of clocks, tick, tick, tick. And depending on when the signal comes in relative to that clock, we’ll indicate to the nervous system that they’re more likely or less likely to be from the same source. So that seems to be rather important in holding our brain together. The second thing is, in general signal processing. That is how information is processed in the brain. Having these oscillations gives information locally a different valence, whether the activity is on the peak of an oscillation and the low point of an oscillation. Now, these oscillations have been known for a long time, but what’s become apparent in the past 15 years or so is that there’s a whole lot of regions of the brain that show significant oscillations that are tied to breathing, including regions like the epicampus, which is very important for learning and memory. The prefrontal cortex is very important in higher function and originally, I think people didn’t pay very much attention to it because the oscillations are relatively slow. We breathe 10 to 20 times a minute, every 4 or 5 seconds, let’s say. And on the time scale of the brain, that seems to be too slow. But now there’s emerging data, there’s emerging data probably over the past ten years from other laboratories, that if you interfere with these breathing oscillations in experimental animals, mostly rodents, their behavior changes. And so there is mounting evidence that somehow this breathing rhythm is playing a role in signal processing. Now that said, any disturbance from the normal pattern will likely produce changes in the way the signal is processing. One analogy I like to use, and I’ve said this before, so people might have heard this, forgive me for repeating it. Let’s imagine a state of depression that it’s caused by activity and a circuit of neurons going around and around like it’s a circuit that’s reverberating. Now, in the nervous system, we know that if activity keeps repeating in the nervous system, it’s likely to strengthen those connections. So now, if you have a circuit that is involved in depression and going round and around and keeps going on, it’s going to get stronger and stronger and stronger, which means that it’s going to be harder to break. Now, how is that dealt with? Well, there’s pharmacological treatments, there’s verbal therapy, but in extreme cases, what has proven to be effective for refractory depression is electroconvulsive shock, where they put massive electrodes on the head and they put a large electrical signal, which is under proper supervision, safe into the brain. And people who have severe depression report they get some relief and if it’s repeated over time, they get more continuous relief. What is that shock doing? Well, in a way, it’s disrupting the activity in that circuit. And we know in the nervous system when activity gets disrupted, it’s quite possibly leading to weakening of synapses. So you weaken the synapses and you do it over time, they can get so weak that the circuit doesn’t work anymore and you get some relief from depression. Now, of course, that electrical ultra shock is very heroic. A more recent approach is to use more focal shock with deep brain stimulation, where electrodes are planted in particular parts of the brain, where disrupting the circuits seems to produce relief for depression. Now, under the assumption that breathing rhythm is present in these circuits, and there’s good evidence that it’s in regions of brain that could be involved, when you disrupt the breathing pattern, that’s going to disrupt the signal processing in that circuit. And if you do it for 30 minutes, you may get some relief. If you do it for 30 minutes a day, day after day after day, you can begin to dissolve the circuit. And moreover, we all know that taking a single deep breath when we’re anxious seems to relax us. So even transiently, if you disrupt the circuit, the signal now takes time to come back to order. So this is part one of my answer. Now, part two is we don’t understand quite how the breathing rhythm is critical in this process of binding and signal processing. But it’s not difficult to imagine that if you change breathing in different ways, you will affect how the circuit that gets disrupted response. So if you breathe fast and shallow or fast and deep, or you breathe box breathing slower, Pranayama, or you focus on active exploration, all these are different kinds of disruptions and it’s very easy to see that each different kind of disruption will produce a different effect. To expand on your question, there’s some discussion, a lot of discussion about nasal versus mouth breathing. And we know that signals that are breathing related coming from the nose are very powerful and affecting brain function. But they’re not the be all and end all. If we block the nasal signal, we still get signals related to breathing going into the brain. And so mouth breathing versus nose breathing, particularly if it’s doing a breathing practice, could very well have different effects. So I did a breathwork detox practice recently and it involved a lot of active expiration. And my personal response was the effect was fairly powerful. But this is a one off. It’s not a controlled experiment, but I would say it had an effect. Whether it was a differential effect versus Pranayama or box breathing, my own experience is not sufficient enough. And I don’t know that there is good experimental data which is always hard to get in humans that could differentiate it. But as a premise, I would argue that it’s quite reasonable.

(Mohit): Well, what’s fascinating is that first of all, your openness to traditional systems and their trace back to science. Generally what we have seen in many fields and spaces is that there’s always a twolane approach which is here’s the science approach and it doesn’t have to do anything with philosophy and here’s the philosophical approach. But there is so much of openness and overlap which is very fascinating to see. 

(Jack): But I can tell you there is one thing we’ve done in the lab recently that really has consolidated my point of view that you described. We were interested in whether controlled breathing in rodents would affect their behavior. Because one can argue that in humans it’s a placebo effect. That if I tell you changing your breathing is going to make you feel better, maybe it has nothing to do with your breathing. Maybe it has to do with the fact that I suggested it. So we spent a lot of time trying to see if we could change the pattern of breathing in rodents in ways that they embrace, that they don’t object to and whether that changes their response to behavior. So these are new experiments but we have one very exciting result when the process of now writing up, we’re able to slow the breathing pattern in an awake mice. These are just mice in a chamber they’re not in and we’re able to slow their breathing by a factor of about ten. So normally they’re breathing four times a second and now they’re breathing every couple of seconds and they seem to be quite fine with it. The best we can observe. We do this for 30 minutes a day for four weeks and then we test them in a standard fear response that psychologists have shown in mice is reflective of fear and relates very much to certain kinds of fear in humans. So it’s a good very well vetted test and we compared the mice that we put through the slow breathing protocol with mice that were handled in exactly the same way but we did not slow their breathing. So we had in 30 minutes a day we just didn’t slow their breathing down. The mice that went through the control mice that didn’t have the slow breathing had a certain level of fear response or mice that went through our conditioning experiments where we slowed their breathing had a remarkable decrease in their fear response. It didn’t go to zero, we didn’t expect to go zero but it was remarkable. It’s as strong in effect as psychologists see with almost any manipulation designed to reduce fear and I have to say this is not my judgment. We are working with Michael Fanzalo who is one of the world’s experts on fear and he himself was quite impressed with this data. So, the fact that you can see it in mice means two things. One is it’s highly unlikely to be a placebo effect because mice don’t believe in placebos and secondly it now gives us a platform to try and investigate mechanisms that are difficult or impossible or unethical to do in humans. So we’re very excited about this and it says that this is a bonafide effect. It’s not someone mesmerizing you into believing something that has nothing to do with breathing. We really think that the data for breathing is now absolute.

Question (Mohit): I also think that this is a fundamental platform shift in terms of how any of these you can say in this case, let’s say, a specific breathing pattern is getting tested from, let’s say, your philosophy to science. You sort of like created like a platform to negate what could be called out as placebo or let’s say any other effect that sort of like dilute the effects of this experiment. And maybe this would be replicated to every other aspect of experimentation. Like in this case, meditation, amygdala activation and the replication in mice. Love to touch on this aspect of I think in some of the other work you mentioned that you had experienced the UCLA meditation and mindfulness work as well. We ourselves have done a bunch of work with UCLA in the past around meditation and mindfulness. I would love to explore some of those aspects as well. But before I get there, one of the things that really intrigued me was the part one of your answers, and I’ll just go back to it was around the physiological phenomena of deep breathing, right? Or sort of like taking what you also call physiological sighs. I find the science fascinating. It’s unbelievably simple and complex at the same time. Given that we don’t realize how many times we sigh, that’s one. On the platform, uh, human platform, we track a metric called respiratory rate. And over time and there is some existing research, but anecdotally you can say that when the immune system is in distress, the respiratory rate changes in humans. And I want to understand, in combination with the physiological sigh, does it have the power of becoming like a biomarker? And first of all, what does it mean for humans? What does sighing mean? And then is there something like sighs per minute or sighs per hour that can actually tell us more about the human body?

Answer (Jack): I’ll be delighted to talk about this. So if you look at the lung, the lung consists the air exchanging space in the lung consists of about 400 – 500 million tiny spheres. Maybe I think about 100 microns in diameter. Forgive me if that number is incorrect, I just don’t remember correctly offhand. They’re very tiny spheres, but there are so many of them, the surface area is about 70 sq mt. About 1/3rd the size of a tennis court. So it’s a huge volume here. But, because the spheres are so small and in order to keep them working properly, they’re lined with a fluid called surfactant. It’s just a liquid. Because they’re so small, they have a small tendency to collapse and they’re collapsing all the time at a very low rate. But when one collapses, that part of the lung can’t be used for gas exchange. Now, if you have 500 million of them, losing one or two is not going to matter, but over time it accumulates. Now, if you ever tried to blow up a wet balloon, a balloon that’s wet on the inside. And if you’ve never done it, take a balloon, put a little water inside, rub it together so the ones sticking and they stick because of surface tension, the water. You realize that when you try and blow it up, it’s not the normal amount of pressure that blows it up. You have to have an extra amount of pressure to overcome the surface tension. Same thing with the lungs. So every time an alveolus collapses, a normal breath is not going to pop it open. You need a deep breath. This is where physiological sighs come in. So every 5 minutes or so you take a deep breath. And to be candid in asking lots of people, including some renowned scientists, how often we sigh, they typically off by an order of magnitude very few lay people believe that we sigh 5 course some people say they signed every minute and that may be true because they’re under a lot of stress but this is physiological. Now, we also have another thing that reduces stress and that relates to emotional state. So in fact, this is how we made this discovery that a particular class of molecules called bombasin related peptides, are critical. When you’re stressed, you secrete from your hypothalamus, which is a part of your brain that produces a lot of very fundamental hormones, these peptides, and at the same time, your sigh rate goes up. And what we did is we then got some of the peptides. We injected it into the pre-Botzinger complex in mice and we found that their sigh rate went from about 40 /hour we originally did it to rats. Excuse me, to like 500 per hour. It was just shocking how powerful it was. And then with the Stanford group, K evin Yako, Mark Krasno and Pung Lee, we went into detail and we found that there was a circuit, a simple circuit that seemed to be responsible for physiological sighs, but these sides that get produced by stress. Elation may have several roles that go beyond any physiological role in needing to inflate the lung. Because if you’re doing it every 5 minutes, you should be fine. But we know that. Any deep breath tends to relax you. So now, if you’re stressed, if the release of these hormones causes you to sign more often, it’s likely to produce a phenomenon where you may be a little bit more relaxed. It may not be enough to relieve all the stress, but you’ll be a bit more relaxed. It also is a way we can communicate to others. If you see someone sigh particularly often, it sends a signal, which you may not recognize consciously, but you recognize that maybe there’s something wrong. This person is stressed. Now, we also sigh when we’re elated, you see a loved one, you see a beautiful sunset. Wow, that’s beautiful. And that’s just another expression. As primates, we use things around our face to communicate, and the control of that is not by the normal volitional control system. There’s a separate control system for this emotional communication. And doing these kinds of sighs could be part of that family of activities that allow you in social settings to communicate what your state of body is.

(Mohit): Wow. So is yawning a master sigh, then? 

(Jack): In that case, forgive me for laughing, because colleagues who feel otherwise well, excuse me. We’re not really sure why we yawn. You know, there’s the notion that it’s you’re bored and it’s contagious. It’s social communication. If in the middle of this podcast I started to yawn, you would begin to wonder if I’m bored, it would not be a good sign of our conversation, even if it’s not meant to be. It could be to help clear the eustachian tubes. So when you get your eustachian tubes clogged, like when a plane lands, you trying and yawn. It may have some reflexes to do with regulating muscle activity. So I have to admit I don’t really know. And I think if you do a deep dive into the literature, there is no single or even a few things that clearly explain why we’re yawning. It’s a bonafide phenomenon and it definitely has effects. But how it evolved, I don’t know. We’re not the only animals that yawn. So it goes beyond just human communication.

(Mohit): The thing I noticed is that just like we mimic each other while yawning. As you mentioned, I probably like sighed a few times while you were sighing as well. Just like probably just mimicking each other

(Jack): Or maybe we just synchronized. So your sigh rate may have synchronized with my sigh rate. So instead of being responsive overtly it’s just we’re synchronizing because when you have oscillations that are about the same frequency, they often now begin to oscillate together. You know the phenomenon of fireflies at dusk, fireflies will be firing randomly, lighting up randomly, but if you’re patient and wait all of a sudden you’ll see that they’ll start synchronizing. And so oscillations like to synchronize. So maybe that’s what’s happening here. 

(Mohit): Yeah, I think we probably would be more simple and complex than we think at the same time. The paradox. Absolutely. But for me to summarize this, if I sigh more number of sighs per hour, if that is a metric for me, if I sigh more, probably that could be a sign of stress event. If I sigh less than what’s the ideal, it could potentially affect my alveoli, my lungs and my lung health overall. So there is sort of like a middle range. 

(Jack): Well, it’s not a range we set consciously, it’s probably set by receptors in the lung which are detecting this alveolial collapse and providing that or we simply could have an oscillation in the pre-Botzinger complex that is not only breath to breath but is much slower. And I have colleagues who have speculated on what that mechanism may be for the intrinsic oscillation that pre-Botzinger complex. Because we know that the alveoli are going to collapse. So we don’t need to wait for a signal, we can just do it in what’s called a feet forward way. We do it every 5 minutes. Now, I’m not a physician and I don’t know what the clinical data is, but I would imagine that there are certain lung diseases where there are problems with the elastic tissue of the lung and the alveoli that the sigh rate may change. But that is not something I have any expertise in.

(Mohit): No, absolutely. And I think one of the things that we would love to probably explore outside this is it’s not in a clinical way. We don’t have medical grade, we do have medical grade devices, but we don’t have FDA approved devices yet. But we have the ability to measure respiratory rate, number of sighs per hour, et cetera. And probably that data is of some work over time and there is longitudinal data.

(Jack):  I would be very excited to see that data because you could correlate it with other aspects that you’re measuring and to see what that correlates with changes in temperature, changes in activity, whether that affects sigh rate. I mean, that would be extremely interesting if you’re able to extract that data. And you would have that data if you’re able to pick out sighs on a reliable basis from your devices.

Question (Mohit): No, absolutely. I don’t think it will be trial grade, but it still would be observational research grade, for sure. So one of those things, just like you mentioned, in combination with temperature, maybe sleep and other factors, measuring sigh might be important. What about, let’s say, glucose metabolism, another aspect of metabolism, which is glucose metabolism, the correlation of, or any sort of connectedness of breathing patterns to glucose metabolism or insulin sensitivity, some of those pathways. Have you explored some of those pathways, or is there existing research on some of those?

Answer (Jack):  I work in a relatively confined silo, and I don’t like to speculate much outside my silo, so I would suspect that there could be a relationship, but I don’t know for a fact. Your blood oxygen levels or could probably deal with some fluctuations, but at the extreme values, I would imagine that there’d be changes. But I don’t have an answer to that. You have to speak to someone who has much more expertise. I’m sorry, I wish I knew. It’s a great question. This is fascinating because we would love to collect more data around this. And I think as a platform, we have the luxury to be wrong always and just present data the way it is without actually just like you said, right? Without actually interpreting it and collecting data. So that in the future, with the hope that somebody actually picks it up and starts with some hypothesis and actually interprets it.

(Jack): Oh, I would encourage you to interpret it. That’s part of the fun. I mean, you know, the hard part is getting the data. You know, getting good data is really hard. And I admire when someone gets really great data and then you have the prerogative to speculate as long as you’re not too dogmatic about the speculation. I think that’s what’s interesting. I would imagine to get data about sighing and breathing in the relationship to all these other physiological variables, you could run it through some very sophisticated statistical analysis and come up with relationships that you need some care in interpreting, but don’t give it away if you don’t have the expertise to get people involved. But the fun of doing science is that interpretive part. And I think you have a platform that is going to get you this very unique set of data of a large population. One of the problems with a lot of human studies is they’re way underpowered 20 people, 50 people. You could do very large numbers and that would be fabulous.

Question (Mohit):  Yeah, absolutely. And it’s sort of like that trade off, right? Less clinical grade, but larger numbers. So might sort of like offset each of these. One might offset for the other, potentially. But this conversation obviously, like energizes me to actually think more about it. Obviously, this is very inspirational, literally. And I think Dr. Feldman, what I would love to learn and this is both for people on the platform and also for myself, is what would you and you have experimented with breathing patterns and methods and you’ve dabbled at both aspects of science, philosophy, et cetera, right? But your absolute favorite, what would be that one breathing method that you incorporate and people incorporate in their life?

Answer (Jack): Well, to be candid, I’m relatively new to this. Often, for a long time I didn’t meditate. I had no breathing practice. And then because of my research, I became interested in it. So I would say I’m a relative novice. I’ve had the good fortune of working with someone in our psychiatry department who has been using breathing therapy in a psychiatric practice for a long time and is doing a human fMRI to look at what’s going on in the higher regions of the brain. And we have a collaborative project. So I become very interested in this. So my practice is relatively simple. I do box breathing and I find it very effective. For me it’s very easy. And moreover, when people ask me about how can I try it, it’s something that’s very simple. It doesn’t require much effort. There are lots of reasonable apps for that. And you know, I’ve tried other forms of breathing practice and I’ve gone through retreats by various groups that have breathing practice and I find them all to be very powerful. But for my own day to day practice, it’s easy for me to find 5 minutes, 10 minutes, 30 minutes to say, okay, I need a break or I’m going to start the day with a better frame of mind and just do it. My pal Andrew Huberman told me that his friends who are Navy Seals use box breathing when they’re in stressful situations and I would imagine that their stressful situations are much more stressful than my day to day situations. So I think that’s a good way to start. I wish I could tell you more and I know that there are individuals who have a very broad range of suggestions for breathing practice and I have tremendous support for them and I think you find whatever works for you. I mentioned this on other podcasts. It’s a little bit like someone who does an exercise. They ask you, well, what exercise should I do? And the response is get up off your butt and walk. It’s easy, it’s painless. And then work from there. And I think it’s the same thing with breathing practice that is you have people who subscribe to your podcast to use your devices and if you ask them to do something too complex to begin with, it might be discouraging and just tell them to try something easier. And I have friends who have followed my advice, which is not too often, and my friends listen to me, but they

uniformly said that they found it to be very helpful. 

(Mohit): I’m inspired and breathless at the same time with this conversation. Well, you’re very kind. This has been really, really fantastic. I’m sure for the listeners, they can finally take a sigh that they’ve learned so much in these compressed few minutes. And I mean, personally, the aspiration would have been to learn so much more. But I think this itself is such a goldmine of information and I really appreciate and from the platform, we really thank you for making time here. One of the things I’m happy about is that both of us have sort of like a common kettlebell in the background. I have one as well. I have something in common with you. I don’t know, I didn’t notice that. Yes, I’ve been just eyeing it. So I’m really happy that there’s something common that we share. But it’s really amazing to have you on the podcast and our aspiration, obviously, or our desire would be in the future to probably do more research together or actually figure out ways to work together, obviously. And if there’s something that we can contribute to from research perspective, of course, you yourself said that this is the fun of science, this is the fun of the research to find your own pathways. So on that note, I’d have to conclude the podcast and look for your final words from the podcast.

(Jack): Well, thank you very much for having me. I would say that participating here not only is interesting for me finding out what your thoughts are, but it’s enlightened self-interest that I really think that the world has not paid enough attention to breathing and I would like it to pay a little bit more attention to what’s going on in the brain. And this is a great way for outreach. I would be delighted to continue to interact with you and if you or any of your colleagues or any of your people participating in the platform want to contact me, they should feel free to do so. Say, I’m hoping to come to India before too long because I have a postdoc in my lab who just accepted a position at the Tata Institute in Bangalore. So he promised he would invite me before too long. So I look forward to coming to India and I will let you know if I do. So maybe we can get together. But it’s been a delight talking to you. You’ve been very kind and generous and I wish you the best of luck moving forward with this. I really would love to see the data as it comes in.

(Mohit): Absolutely. And thank you, Dr. Feldman. We are pretty much based out of Bangalore, so we would absolutely love to host you there when you’re around. But thank you for making time today and really appreciate you for all the golden nuggets of knowledge. And on that note, I would love to conclude the podcast.

(Jack): Okay, bye now. Have a great day.

(Mohit): All right, thank you. Thank you, Dr. Feldman.

Outro (Mohit): Well, that was like an explosion of knowledge bomb, wasn’t it? Dr. Feldman had so many golden nuggets of information to share and talk about the upcoming research in this space. Breathing seems so simple on the surface, and yet the mechanisms are very complex. I hope after listening to this episode, you are going back with a better and simplified understanding of the breathing mechanisms and with a few more layers of added context. If you loved this episode, don’t forget to share this around and also on your social media handles. Tag us @UltrahumanHQ. Your support goes a long way. Don’t forget to subscribe to the Ultrahuman Podcast. We would love to hear from you on what we are doing here. So rate and review the Ultrahuman Podcast on Apple  Podcasts and Spotify. As I sign off, don’t forget to be at your metabolic health journey. Treat every day as a gift and do something towards improving yourself. I’ll see you next week with a new guest and a new episode.

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