Huberman Lab - Dr. Jack Feldman: Breathing for Mental & Physical Health & Performance

Starting point is 00:00:00 Welcome to the Huberman Lab podcast where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. Today my guest is Dr. Jack Feldman. Dr. Jack Feldman is a distinguished professor of neurobiology at the University of California, Los Angeles. He is known for his pioneering work on the neuroscience of breathing. We are all familiar with breathing and how essential breathing is to life. We require oxygen and it is only by breathing that we can bring oxygen to all the cells of our brain and body. However, as the work from Dr. Feldman and

Starting point is 00:00:40 colleagues tells us, breathing is also fundamental to organ health and function at a enormous number of other levels. In fact, how we breathe, including how often we breathe, the depth of our breathing and the ratio of inhales to exhales actually predicts how focused we are, how easily we get into sleep, how easily we can exit from sleep. Dr. Feldman gets credit for the discovery of the two major brain centers that control

Starting point is 00:01:07 the different patterns of breathing. Today, you'll learn about those brain centers and the patterns of breathing they control, and how those different patterns of breathing influence all aspects of your mental and physical life. What's especially wonderful about Dr. Feldman and his work is that it not only points to the critical role of respiration in disease, in health, and in daily life, but he's also a practitioner. He understands how to leverage particular aspects of the breathing process in order to bias

Starting point is 00:01:35 the brain to be in particular states that can benefit us all. Whether or not you are a person who already practices breathwork or whether or not you're somebody who simply breathes to stay alive, By the end of today's discussion, you're going to understand a tremendous amount about how the breathing system works and how you can leverage that breathing system toward particular goals in your life. Dr. Feldman shares with us his own particular breathing protocols that he uses and he suggests different avenues for exploring respiration in ways that can allow you, for instance, to be more focused for work, to disengage from work

Starting point is 00:02:08 and high stress endeavors to calm down quickly. And indeed, he explains not only how to do that, but all the underlying science in ways that will allow you to customize your own protocols for your needs. All the guests that we bring on the Huberman Lab podcast are considered at the very top of their fields. Today's guest, Dr. Feldman, podcast are considered at the very top of their fields. Today's guest, Dr. Feldman, is not only at the top of his field, he founded the field.

Starting point is 00:02:30 Prior to his coming into neuroscience from the field of physics, there really wasn't much information about how the brain controls breathing. There was a little bit of information, but we can really credit Dr. Feldman and his laboratory for identifying the particular brain areas that control different patterns of breathing and how that information can be leveraged towards health, high performance, and for combating disease. So today's conversation, you're going to learn a tremendous amount from the top researcher in this field. It's a really wonderful and special opportunity to be able to share his knowledge with you.

Starting point is 00:03:00 And I know that you're not only going to enjoy it, but you are going to learn a tremendous amount. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens.

Starting point is 00:03:23 Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or twice today is that it helps me cover all of my basic nutritional needs. It makes up for any deficiencies that I might have. In addition, it has probiotics, which are vital for microbiome health. I've done a couple of episodes now on the so-called gut microbiome and the ways in which the microbiome interacts with your immune system, with your brain to regulate mood, and essentially with every biological system relevant to health throughout your brain and body.

Starting point is 00:04:01 With athletic greens, I get the vitamins I need, the minerals I need, and the probiotics to support my microbiome. If you'd like to try athletic greens, you can go to athleticgreens.com slash Huberman and claim a special offer. They'll give you five free travel packs plus a year supply of vitamin D3K2. There are a ton of data now showing that vitamin D3 is essential for various aspects of our brain and body health, even if we're getting a lot of sunshine, many of us are still deficient in vitamin D3. And K2 is also important because it regulates things like cardiovascular function, calcium in the body, and so on.

Starting point is 00:04:32 Again, go to atlettagreens.com slashubramin to claim the special offer of the five free travel packs and the year supply of vitamin D3 K2. Today's episode is also brought to us by Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are an element and those are sodium, magnesium and potassium, but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes

Starting point is 00:05:00 for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body. If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells function properly and all our bodily systems can be optimized. If the electrolytes are not present and if hydration is low, we simply can't think, as well as we would otherwise. Our mood is off, hormone systems go off, our ability to get into physical action, to engage in endurance and strength, and all sorts of other things is diminished. So with element, you can make sure that you're staying on top of your hydration and that you're getting the proper ratios of electrolytes. If you'd like to try element, you can go to drinkelement. That's LMNT.com slash Huberman, and you'll get a free element sample pack with your purchase.

Starting point is 00:05:45 They're all delicious. So again, if you wanna try element, you can go to elementlmnt.com slash Huberman. One quick mention before we dive into the conversation with Dr. Feldman. During today's episode, we discuss a lot of breathwork practices, and by the end of the episode, all of those will be accessible to you.

Starting point is 00:06:01 However, I'm aware that there are a number of people out there that wanna go even further into the science and practical tools of breathwork. And for that reason, I want to mention a resource to you. There is a cost associated with this resource, but it's a terrific platform for learning about breathwork practices and for building a number of different routines that you can do or that you could teach. It's called our breathwork collective. I'm not associated with the breathwork collective, but Dr. Feldman is an advisor to the groove. And they offer daily live guided breathing sessions and an on-demand library that you can practice anytime,

Starting point is 00:06:32 free workshops on breath work. And these are really developed by experts in the field, including Dr. Feldman. So as I mentioned, I'm not on their advisory board, but I do know them in their work, and it is of the utmost quality. So anyone wanting to learn or teach breath work could really benefit from this course, I believe.

Starting point is 00:06:48 If you'd like to learn more, you can click on the link in the show notes or visit our breath collective dot com slash huberman and use the code huberman at checkout. And if you do that, they'll offer you $10 off the first month. Again, it's our breath collective dot com slash huberman to access the our breath collective. And now for my conversation with Dr. Jack Feldman. Thanks for joining me today. It's a pleasure to be here, Andrew. Yeah, it's been a long time coming.

Starting point is 00:07:12 You're my go-to source for all things, respiration. I mean, I breathe on my own, but when I want to understand how I breathe and how the brain and breathing interact, you're the person I call. Well, do my best, as you know, there's a lot that we don't understand, which still keeps me employed and engaged, but we do know a lot. When we start off by just talking about what's involved in generating breath, and if you

Starting point is 00:07:38 would, could you comment on some of the mechanisms for rhythmic breathing versus non-rhythmic breathing? Okay. So on the mechanical side, which is obvious to everyone, we want to have a flow in, inhale, and we need to have a flow out. And the reason we need to do this is because for body metabolism we need oxygen. And when oxygen is utilized through the aerobic metabolic process, we produce carbon dioxide. And so we have to get rid of the carbon dioxide that we produce,

Starting point is 00:08:16 in particular because the carbon dioxide affects the S-a-base balance of the blood, the pH. And all living cells are very sensitive to what the pH value is. So your body is very interested in regulating that pH. So we have to have enough oxygen for our normal metabolism, and we have to get rid of the CO2 that we produce. So how do we generate this airflow?

Starting point is 00:08:40 Well, the air comes into the lungs. We have to expand the lungs. And it's the lungs expand. Basically, it's like a balloon that you would pull apart. The pressure inside that balloon drops and air will flow into the balloon. So we expand, pull a pressure on, put pressure on the lung to pull it apart. That lowers the pressure in the air sacs called LVLI and air will flow in because pressure outside the body is higher than pressure inside the body when you're doing this expansion, when you're inhaling.

Starting point is 00:09:13 What produces that? Well, the principal muscle is a diaphragm, which is sitting inside the body just below the lung. And when you want to inhale, you basically contract the diaphragm and it pulls it down. And as it pulls it down, it's inserting pressure forces on the lung, the lung wants to expand. At the same time, the rib cage is going to rotate up and out, and therefore expanding the cavity, the thoracic cavity.

Starting point is 00:09:42 At the end of inspiration, under normal conditions when you're at rest, you just relax. And it's like pulling on a spring. You pull down a spring and you let go and relax. So you inhale and you exhale. Inhale, relax and exhale. So the exhale is passive. At rest, it's passive. We'll get into what happens when you need to increase the amount of air you bring in because your ventilation, your metabolism goes up like during exercise. Now the muscles themselves, skeleton muscles, don't do anything unless the nervous system tells them to do something. And when the nervous system tells them to do something, they contract.

Starting point is 00:10:28 So there are specialized neurons in the spinal cord and above the spinal cord, the region called the brainstem, which go to respiratory muscles, in particular for inspiration, the diaphragm, and the external intercostal muscles in the rib cage, and they contract. So these respiratory muscles, these respiratory muscles become active. And they become active for a period of time, then they become silent. And when they become silent, the muscles then relax back to their original resting level.

Starting point is 00:11:06 And they become silent, the muscles then relax back to their original resting level. Where does that activity in these neurons that innovate the muscle, which are called motor neurons, where does that originate? Well, this was a question that's been banding around for thousands of years. And when I was a beginning a system professor, it was fairly high priority for me to try and figure that out, because I wanted to understand where this rhythm of breathing was coming from, and you couldn't know where it was coming from until you knew where it was coming from. I didn't phrase that properly. You couldn't understand how it was being done until you know where to look.

Starting point is 00:11:44 So we did a lot of experiments which I can go into detail and finally found there was a region in the brain stem. That's once again this region sort of above the spinal cord, which was critical for generating this rhythm. It's called the pre-butts in the complex. And we could talk about how that was named. This small site which contains in humans a few thousand neurons, it's located on either side and it works in tandem, and

Starting point is 00:12:14 every breath begins with neurons in this region beginning to be active, and those neurons then connect ultimately to these motor neurons going to the diaphragm and to the external intercostals, causing them to be active and causing this inspiratory effort. When the neurons in the pre-butt-seer complex finish their burst of activity, then inspiration stops. And then you begin to exhale

Starting point is 00:12:46 because of this passive recall of the lung and rib cage. Could I just briefly interrupt you to ask a few quick questions before we move forward in this very informative answer. And the two questions are, is there anything known about the activation of the diaphragm and the intercostal muscles between the ribs as it relates to nose versus mouth breathing or are they activated in the equivalent way regardless of whether or not someone is breathing through their nose or mouth?

Starting point is 00:13:24 I don't think we fully have the answer to that. Clearly there are differences between nasal and mouth breathing. At rest, the tendency is to do nasal breathing because the air flows that are necessary for normal breathing are easily managed by passing through the nasal cavities. However, when your ventilation needs to increase like during exercise, you need to move more air. You do that through your mouth because the airways are much larger than and therefore you can move much more air. But at the level of the intercostals and the diaphragm, their contraction is almost agnostic to whether or not the nose and mouth are open. Okay, so if I understand correctly, there's no reason to suspect that there are particular, perhaps even non-overlapping sets of neurons in pre-butts singer area of the brainstem

Starting point is 00:14:22 that triggered nasal versus mouth inhales. No, I would say that there's, it's not that the prebutton complex is not concerned and cannot influence that, but it does not appear as if there's any modulation of whether or not it's where the air is coming from, whether it's coming through your nasal passages or through your mouth. Right. Thank you. And then the other question I have is that these intercostal muscles between the ribs, they move the ribs up and out, if I understand correctly, and the diaphragm are those skeletal,

Starting point is 00:14:57 or as the breads would say, skeletal muscles, or smooth muscles, what type of muscle are we talking about here? As I said earlier, these are skeleton, I didn't say there were skeleton muscles, but there are muscles that need neural input in order to move. You talked about smooth muscles. They are specialized muscles like we have in the gut and in the heart. And these are muscles that are capable of actually contracting and relaxing on their own. So the heart beats, it doesn't need neural input in order to beat. muscles that are capable of actually contracting and relaxing on their own.

Starting point is 00:15:25 So the heart beats, it doesn't need noral input in order to beat. The noral inputs modulate the strength of it and the frequency, but they beat on their own. The skeletal muscles involved in breathing are need noral input. Now there are smooth muscles that have an influence on breathing and these are muscles that are lining the the airways. And so the airways have smooth muscle and when they become activated the smooth muscle can contract or relax. And when they contract inappropriately is when you have problems breathing like an asthma,

Starting point is 00:16:06 asthma is a condition where you get inappropriate constriction of the smooth muscles of the ears. So there's no reason to think that an asthma, that the pre-butts singer, or these other neuronal centers in the brain that can, that activate breathing, that they are involved or causal for things like asthma. As of now, I would say the preponderance of evidence is that it's not involved,

Starting point is 00:16:28 but we've not really fully investigated that. Thank you. Sorry to break your flow, but I was terribly interested in knowing answers to those questions and you provided them. So thank you. Now, remind me again, where I was in my... We were just landing in Pre-Buttsinger,

Starting point is 00:16:45 and we will return to the naming of Pre-Buttsinger, because it's a wonderful and important story, really. I think people should be aware of, but yeah, maybe you could march us through the brain centers that you've discovered and others have worked on as well if that control breathing, Pre-tsinger as well as relating structures. So when we discovered the prebuttsinger,

Starting point is 00:17:10 we thought that it was the primary source of all rhythmic respiratory movements, both inspiration and expiration. The notion of a single source is like day or night. It's like they're all coming, they're all of the same origin that the Earth rotates and day follows night. And we thought that the pre-buttzing of complex would be inhalation, exhalation.

Starting point is 00:17:37 And then in a series of experiments we did in the early part of 2000, we discovered that there seemed to be another region which was dominant in producing expatory movements. That is the exhalation. We had made a fundamental mistake with the discovery of the pre-buttsinger not taking into account that at rest, expatory muscle activity or exhalation is passive.

Starting point is 00:18:12 So if that's the case, a group of neurons that might generate active exploration that is to contract the expatory muscles, like the abdominal muscles, or the internal intercostals, are just silent. We just thought it wasn't there was coming from one place. But we got evidence that in fact, it may have been coming from another place. And following up on these experiments,

Starting point is 00:18:36 we discovered that there was a second oscillator, and that oscillator is involved in generating what we call active expiration. That is this actively, if I go, shh, yeah. Or when you begin to exercise, you have to go, and actually move that air out. This group of cells, which is silent the dress, suddenly becomes active to drive those muscles.

Starting point is 00:19:03 And it appears that it's an independent oscillator when maybe you could just clarify if people wouldn't oscillate or is. Okay, an oscillator is something that goes in a cycle. So you can have a pendulum as an oscillator going back and forth. The earth is an oscillator because it goes around and it's day and night.

Starting point is 00:19:22 Some people's moods are oscillating. Oscillating. And it depends how regular they are. You can have oscillators that are highly regular that are in a watch, or you can have those that are sporadic or episodic. Breathing is one of those oscillators that for life has to be working continuously 24-7.

Starting point is 00:19:43 It starts in the late end of third trimester because it has to be working when you're born and basically works throughout life. And if it stops, if there's no intervention, beyond a few minutes, it will likely be fatal. What is this second oscillator called? Well, we found that in a region around the facial nucleus. So we initially, when this region was initially identified, we thought it was involved in sensing carbon dioxide. It was what we call essential chemoreceptor.

Starting point is 00:20:19 That is, we want to keep carbon dioxide levels, particularly in the brain at a relatively stable level, because the brain is extraordinarily sensitive to changes in pH. If there's a big shift in calmed oxide, there's a big shift in brain pH, and that'll throw your brain, if I can use the technical term, out of whack. So you want to regulate that. The way to regulate something in the brain is you have a sensor in the brain.

Starting point is 00:20:47 And others basically identified that the eventual surface of the brain stem, that is the part of the brain stem, that's on this side, was critical for that. And then we identified a structure that we was near the trapezoid nucleus. It was not named in any of these noranatomegal atlases. So we just picked the name out of the hat and we called it the retro trapezoid nucleus.

Starting point is 00:21:16 Actually, clarify for people when Jack is saying trapezoid, doesn't mean the trapezoid muscles. Trapezoid refers to the shape of this nucleus, this cluster of neurons. Paraphrasial makes me think that this general area is involved in something related to mouth or face. Is it an area rich with neurons controlling other parts of the face?

Starting point is 00:21:39 Eyeblinks, nose twitches, lip curls, lip smacks. If you go back in an evolutionary sense, and a lot of things that are hard to figure out begin to make sense when you look at the evolution of the nervous system, when control of facial muscles going back to more primitive creatures, because they had to take things in their mouth for eating. So we call that the face sort of developed their eyes where they are the mouth is there. These nuclei, the motor that contained the motor neurons, a lot of the control systems for them developed in the immediate vicinity. So if you think about the face, there's a lot of sub-nuclear eye around there that had

Starting point is 00:22:26 various holes at various different times in evolution. And at one point in evolution, the facial muscles were probably very important in moving fluid in and out of the mouth and moving air in and out of the mouth. And so, part of these many different sub-nlei now seems to be in mammals to be involved in the control of expatory muscles. But we have to remember that mammals are very special when it comes to breathing because we're the only class of vertebrates that have a diaphragm. If you look at amphibians and reptiles, they don't have a diaphragm. And the way they breathe is not by actively inspiring and passively expiring. They breathe by actively expiring and passively inspiring because they don't have a powerful inspiratory muscle. And somewhere along the line, the diaphragm developed.

Starting point is 00:23:27 And there are lots of theories about how it developed. I don't think it's particularly clear. There was something you can find in alligators and lizards that could have turned into a muscle that was the diaphragm. The amazing thing about the diaphragm is that it's mechanically extremely efficient. And what do I mean by that?

Starting point is 00:23:49 Well, if you look at how oxygen gets from outside the body into the bloodstream, the critical passage is across the membrane in the lung. It's called the alveolar capillary membrane. The alveolis is part of the lung, and the blood runs through capillaries, which are these the smallest tubes in the circulatory system. And at that point, oxygen can go from the air-filled alveolis into the blood, which is amazing. I find that amazing. Even though it's just purely mechanical, the idea of these little sacks in our lungs, we inhale and the air goes in and literally the oxygen can pass into the bloodstream.

Starting point is 00:24:32 It passes into the bloodstream, but the rate of which it passes will depend on the characteristics of the membrane, how, what the distance is between the alveolis and the blood vessel, the capillary. But the key element is the surface area. The bigger the surface area, the more oxygen that can pass through. It's entirely a passive process. There's no magic about making oxygen go in. Now, how do you get a pack a large surface area

Starting point is 00:25:04 in a small chest? Well, you start out with one tube, which is the trachea. The trachea expands. Now, you have two tubes, then you have four tubes, and it keeps branching. At some point, at the end of those branches, you put a little sphere, which is an alveolis. And that determines what the surface area is going to be. Now, you then have a mechanical problem. You have the surface area.

Starting point is 00:25:32 You have to be able to pull it apart. So imagine you have a little square of a last-to-crime brain. It doesn't take a lot of force to pull it apart. But now, if you increase it by 50 times, you need a lot more force to pull it apart. But now if you increase it by 50 times, you need a lot more force to pull it apart. So amphibians who were breathing not by compressing the lungs and then just passively expanding it

Starting point is 00:25:56 weren't able to generate a lot of force. So they have relatively few branches. So if you look at the surface area that they pack in their lungs, grow it up to their body size, it's not very impressive. Whereas when you get to mammals, the amount of branching that you have is you have four to five hundred million alveoli. How, if we were to take those four to five million, I've, uh, four hundred million, four hundred million, four hundred million, excuse me,

Starting point is 00:26:27 um, and lay those out flat, what sort of surface area are we talking about? About 70 square meters, which is about a third the size of a tennis court. Wow. So you have a membrane inside of you, a third the size of a tennis court, is that you actually have to expand every breath,

Starting point is 00:26:44 and you do that without exerting much of a, you don't feel it. And that's because you have this amazing muscle, the diaphragm, which because of its positioning, just by moving two thirds of an inch down, is able to expand that membrane enough to move air into the lungs. Now, the at rest, the volume of air in your lungs is about two and a half liters. Do we need to convert that to quartz? No. It's about two and a half liters. When you take a breath, you take another 500 ml, a half a liter. That's the size maybe a little of my fist. So you're increasing the volume by 20 percent. But you're doing that by pulling on this 70 square meter membrane. But that's enough to bring enough fresh air into the lung to mix in with the air that's already there.

Starting point is 00:27:40 That the oxygen levels in your your bloodstream goes from a partial pressure of oxygen, which is 40 millimeters of mercury to 100 millimeters of mercury. So that's a huge increase in oxygen, and that's enough to sustain normal metabolism. So we have this amazing mechanical advantage by having a diaphragm. Do you think that our brains are larger than that of other mammals in part because of the amount of oxygen that we have been able to bring into our system? I would say a key step in the ability to develop a large brain that has a continuous the me and for oxygen is a diaphragm. Without a diaphragm, you're an amphibian. And there's another solution to increasing oxygen uptake, which is the way

Starting point is 00:28:39 birds breathe, but birds have other limitations and they still can't get brains as big as mammals have. So we, the brain utilizes maybe 20% of all the oxygen that we intake, and it needs it continuously. The brain doesn't want to be neglected. So this puts certain demands on breathing system. In other words, you can't shut it down for a while, which poses other issues. You're born, and you have to mature. You have the small body, you have a small lung, you have a very planned rib cage.

Starting point is 00:29:17 And now you have to develop into an adult, which has a stiffer rib cage. And so there are changes happening in your brain and in your body, where breathing, the neural control of breathing has to change on the fly. It's not like for things like vision, where you have the opportunity to sleep.

Starting point is 00:29:36 And while you're sleeping, the brain is capable of doing things that are not easy to doing during wakefulness, like the construction crew comes in during sleep. Breathing has been, the change in breathing has been described as trying to build an airplane while it's flying. Basically what Jack is saying is that respiration science is more complex and hardworking than vision science, which is the direct jab at me.

Starting point is 00:30:01 Some of you might have missed, but I definitely did not miss. And I appreciate that you always take the opportunity, like a good New Yorker to, to, you know, give me a good healthy intellectual jab. A question related to diaphragmatic breathing versus non-d diaphragmatic breathing, because the way you describe it, the diaphragm is always involved. But, you know, over the years, whether it it be yoga class or a breathwork thing, or you hear online, that we should be breathing with our diaphragm, that rather than lifting our ribcage when we breathe, and our chest that it is healthier in air quotes, or better somehow to have the belly expand when we inhale.

Starting point is 00:30:42 I'm not aware of any particular studies that really examine the direct health benefits of diaphragmatic versus non-d diaphragmatic breathing, but if you don't mind commenting on anything you're aware of as it relates to diaphragmatic versus non-d diaphragmatic breathing, whether or not people tend to be diaphragmatic breathers by default, et cetera, that would be, I think, interesting to a number of people. Well, I think by default, we are obligate diaphragm breathers. I, there may be pathologies where the diaphragm is compromised and you have to use other muscles.

Starting point is 00:31:17 And that's a challenge. It is certainly addressed. Other muscles can take over. But if you need to increase your ventilation, the diaphragm is very important. It would be hard to increase your ventilation otherwise. Do you pay attention to whether or not you are breathing in a manner where your belly goes out a little bit as you inhale? Because I can do it both ways, right?

Starting point is 00:31:45 I can inhale, bring my belly in, or I can inhale, push my diaphragm and belly out, the diaphragm out. But, and that's interesting, right? Because it's a completely different muscle set for each version. Well, in the context of things like breath practice, I'm a bit agnostic about the effects of some of the different patterns of breathing.

Starting point is 00:32:13 Clearly some are gonna work through different mechanisms and we can talk about that. But at certain level, for example, whether it's primarily diaphragm where you move your abdomen or not, I am agnostic about it. I think that the changes that breathing induces in emotion and cognition, I have different ideas about what the influence is, and I don't see that primarily as how which particular muscles

Starting point is 00:32:44 you're choosing. but that just could be my own prejudice. Okay. We will return to that as a general theme in a little bit. I want to ask you about siging. One of the many great gifts that you've given us over the years is an understanding of these things that we call physiological size. Could you tell us about physiological size? What's known about them? What your particular interest in them is and what they're good for? Very interesting and important question.

Starting point is 00:33:24 very interesting and important question. So everyone has a sense of what a sigh is. We, certainly when we're emotional in some ways, we're stressed, we're particularly happy, we'll take a sigh. It turns out that we're sighing all the time. And when I would ask people who are not particularly knowledgeable that haven't read my papers or James Nester's book or listen to your podcast, they're usually off by toward as a magnitude about how frequently

Starting point is 00:33:59 we sigh on the low side. In other words, they say, once hour, you know, 10 times a day, we sigh about every five minutes. And I would encourage anyone who finds that to be a unbelievable fact, is to lie down in a quiet room and just breathe normally, just relax, just let go, and just pay attention to your breathing, and you'll find that every couple of minutes you're taking a deep breath, and you can't stop it. You know, it just happens.

Starting point is 00:34:36 Now why? Well, we have to go back to the lung again. The lung has these 500 million LVLI, and they're very tiny. They're 200 microns across. So they're really, really tiny. And you can think of them as fluid fill, they're fluid line. And the reason they're fluid line has to do with the esoteric of the mechanics of that. It makes it easier to stretch them with this fluid line, which is called surfactant.

Starting point is 00:35:09 And surfactant is important during development that is a determining factor in the when premature infants are born, if they do not have lungs surfactant, that makes it much more challenging to take care of them, than after they have lungs surfactant, which is sometime, if I remember correctly, in the late second, early third trimester, which it appears. In any case, it's fluid line. Now think of a balloon that you would blow up, but now, before you blow it up, fill

Starting point is 00:35:39 the balloon with water. Squeeze all the water out, and now, when you squeeze all the water out and now when you squeeze all the water out you notice the size of the balloon stick to each other. Why is that? Well that's because water has what's called surface tension and when you have two surfaces of water together they actually tend to stick to each other. Now when you try and blow that balloon up you know that it you'll notice, if you've ever done it before, that the balloon is a little harder to inflate than if we're dry on the inside. Why is that? Because you have to overcome that surface tension.

Starting point is 00:36:17 Well, your LVLI have a tendency to collapse. There's 500 million of them. They're not collapsing at a very high rate, but it's a slow rate that's not trivial. And when Alveilus collapses, it no longer can receive oxygen or take carbon dioxide out. It's sort of taken out of the equation. Now, if you have 500 million of them and you lose 10, no big deal.

Starting point is 00:36:44 But if they keep collapsing, you can lose a significant part of this surface area if you're lung. Now, a normal breath is not enough to pop them open. But if you take a deep breath, it pops them open. Through nose or mouth. It doesn't matter. It's just increased that lung volume because you're just pulling on the lungs, they'll pop open about every five minutes.

Starting point is 00:37:12 And so we're doing it every five minutes in order to maintain the health of our lung. In the early days of mechanical ventilation, which was used to treat polio victims, who had weakness of their respiratory muscles. They'd be putting these big steel tubes. And the way they would work is that the pressure outside the body would drop.

Starting point is 00:37:36 That would put an expansion pressure on the lungs, excuse me, on the ribcage. The ribcage would expand. And then the lung would expand. and then the long would expand. And then the pressure would go back to normal, and the longer ribcage would go back to normal. This was great for getting ventilation, but there was a relatively high mortality rate.

Starting point is 00:37:59 It was a bit of a mystery, and one solution was to just give bigger breaths. They gave bigger breaths in a mortality rate drop. And it wasn't until I think it was the 50s where they realized that they didn't have to increase every breath to be big, what they needed to do is every so often they had to have one big breath. So they gave a couple of minutes in normal breaths and then one big breath just mimicking the physiological size and they're the mortality rate drops significantly. And if you see someone on event, event a later in the hospital, if you watch every couple

Starting point is 00:38:36 of minutes that you see the membrane move up and down, every couple of minutes there'll be a super breath and that pops it open. So there are these mechanisms for these physiological size. So just like with the collapse of the lungs, where you need a big pressure to pop it open, it's the same thing with the alveolar. You need a bigger pressure, and a normal breath is not enough.

Starting point is 00:39:02 So you have to take a big inhale. And when nature is done, is instead of requiring us to remember to do it, it does it automatically. And it does it about every five minutes. And one of the questions we asked is, how is this happening? Why every five minutes?

Starting point is 00:39:21 What's doing it? And we got into it, still a back door. Typical of the way a lot of science could stand. This is serendipitous event where you run across a paper and something clicks and you just, you know, you follow it up. Sometimes you go down blind ends, but this time doubt to be incredibly productive. One of the guys in my lab was reading a paper about stress and during stress lots of things happen in the body.

Starting point is 00:39:55 One of which is that type of thaleness, which is very reactive to body state, releases peptides, which are specialized molecules which then circulate throughout the brain and body, that particular effects usually to help deal better with the stress. And one class of the peptides that are released are called bambasin related peptides. And you also realize, because he was a breathing guy, and when you stress, you sigh more. So we said, all right, maybe they're related.

Starting point is 00:40:30 Bambasin is relatively cheap to buy. We said, let's buy some bambasin thrown in the brains, then let's see what happens. And one of the nice things about some experiments that we tried to design is to fail quickly. So here we had the idea, we throw bombison in and if bombisoned, then nothing, nothing lost, maybe $50 to buy the bombison. But if it did something, it might be of some interest.

Starting point is 00:40:59 So we, one afternoon, he did the experiment and he comes to me and says, I won't quote exactly what he said, because that might need to be censored. But he said, look at this. And it was in a rat. Rats sigh about every two minutes. They're small than we are, and they need to sigh more often. This I rate went from 20 to 30 per hour to 500 per hour when you put bombasin into the prebutts in a complex.

Starting point is 00:41:30 Amazing. And the way did that is it took a very, very fine glass needle and anesthetized a rat and inserted that needle directly into the prebutts in a complex. So it wasn't a generalized delivery of the peptide. It was localized to the prebutts in a complex. So it was a generalized delivery of the peptide. It was localized to the prebutts in the psi rate went through the roof. And I would add that that was an important experiment to deliver the bombison directly to that site

Starting point is 00:41:57 because one could have concluded that the injection of the bombison increased sign because it increased stress rather than directly increase sign. Amongst hundreds of other possible interpretations, so the precision here is very important and that goes back to what I said at the very beginning, knowing where this is happening allows you to do the proper investigations. If we didn't know where the inspiratory rhythm

Starting point is 00:42:21 was originating, we never could have done this experiment. And so then we done this experiment. Then we did another experiment. We said, okay, what happens if we take the cells in the pre-buttsinger that are responding to the peptide? So, neurons will respond to a peptide because they have specialized receptors for that peptide. And not every neuron expresses those receptors in the pre-budset complex, probably a few hundred out of thousands. So we used the technique we had used before. And this is a technique developed by Doug Lappi down in San Diego, where you could take a peptide and conjugate it with a molecule called saprin. Saprin is a plant-arive molecule which is a cousin to ricin.

Starting point is 00:43:16 And many of your listeners may have heard of ricin. It's a rhizonal toxin. It's very nasty. It's a single, you know, stab with an umbrella will kill you, which is a something that's supposedly happened to a Bulgarian diplomat by a Russian operative on a bridge in London. He got stabbed. And the way rice and works is it goes inside a cell, crosses the cell membrane, goes inside the cell, kills the cell, and then it goes to the next cell, and then the next cell, and then the next cell.

Starting point is 00:43:49 It's extremely dangerous. In fact, it's firstly impossible to work on in a lab in the United States. They've brought lecture and culture. Right. Because we've worked with saparin many times. Saparin is safe because it stays outside of cells. Please, nobody do that, even though it doesn't cross-seal membranes.

Starting point is 00:44:10 Please, nobody injects saprin whether or not you are a operative or otherwise. Thank you, Andrew, for protecting me there. So, but what Doug Lappey figured out is that when a person is a receptor, there's when a molecule binds to its receptor, in many cases, that receptor ligand complex gets

Starting point is 00:44:40 pulled inside the cell. So, of course, when the membrane is in the cell, inside the cell. It's all like you can't go to the dance alone, but if you're coupled up, you get in the cell. So it goes from the membrane of the cell inside the cell. It's like you can't go to the dance alone, but if you're coupled up, you get in the door. That's right. So when he figured out, as he put saparin to the peptide, the peptide binds to its receptor, it gets internalized. And then when it's inside the cell,

Starting point is 00:45:00 saparin does the same thing the rice and does. It kills the cell, but then it can't go into the next cell. So the only cells that get killed or the more polite term oblated are cells that express that receptor. So if you have a big conglomeration of cells, you have a few thousand and only 50 of them express that receptor, then you inject the saprin, conjugated to the ligand, to the peptide,

Starting point is 00:45:27 and only those 50 cells die. So we took bombison, conjugated to saprin, injecting the prebutter complex of rats, and it took about a couple of days for the saprin to actually oblite cells. And what happened is that the mice started sighing less and less, excuse me, the rats started sighing less and less and less and less and less and essentially stopped sighing.

Starting point is 00:45:58 So your student or postdoc was it murdered these cells and as a consequence the sign goes away. What was the consequence of eliminating sign on the internal state or the behavior of the rats? In other words if one can't sigh, it generates physiological size, what is the consequence on state of mind? Do you would imagine that carbon dioxide would build up more readily or To higher levels in the bloodstream and that the animals would be more stressed that that's the kind of logical extension of the way we set it up It was less benign than that When the animals got to the point where they were ensying, then we did not determine this, but the presumption was that their

Starting point is 00:46:52 lung function significantly deteriorated and their physical health deteriorated significantly, and we had to sacrifice them. So I can't tell you whether they were stressed or not, but their breathing got to be significantly deteriorated that we sacrifice them at that point. Now we don't know whether that is specifically related to the fact that they didn't sigh or that it's, there was secondary damage due to the fact that some

Starting point is 00:47:25 so-stuy. So we never determined that. Now, after we did this study, to be candid, it wasn't a high priority for us to get this out the door and publish it. So it stayed on the shelf. Then I got a phone call from a graduate student at Stanford, Kevin Yakle, who starts asking me all these interesting questions about breathing. And I'm happy to answer them, but at some point it concerned me because he was working for a renowned biochemist who worked on long and josophila fruit flies, more crafts now. And I said, I'm an extort colleague. And I said, why are you asking me this?

Starting point is 00:48:13 And he said, I was an undergraduate UCLA and you gave a lecture on my undergraduate class and I was curious about breathing ever since. So that's one of those things which as a professor you love to hear that actually is something you really affected the life of a student. When you birthed a competitor but you had only yourself to blame. No, I don't look at that as a competitor. I think that there's enough interesting things to go on. I know some of our neuroscience colleagues say you can work in my lab but then when you leave my lab you got to work on something different. No one I ever trained with said that. It's open field. You you gotta work on something different. No one I ever trained with said that.

Starting point is 00:48:45 It's open field. You wanna work on something you hop in the mix. And, but there are people like that, you're a scientist like that. I never felt like that. I hear that their breathing apparatus are disrupted and it causes a brain dysfunction that leads to the behavior just described.

Starting point is 00:48:59 It's actually not true. But in terms of the, so, before you, we talk about the beautiful story with Yackel and Krasnoyl and Feld Lab, I want to just make sure that I understand. So if physiological size don't happen, basically breathing overall suffers. Well, that would go back to the observations in polio victims and these ion lungs where the principal deficit was there was no hyperinflation of the lungs and they many of them deteriorated and died. And just to stay on this one more moment before we move to what you were about to describe, we hear often that people will overdose on drugs of various kinds because they stop breathing.

Starting point is 00:49:53 So barbituids, alcohol combined with barbituids is a common cause of death for drug users and contraindications of drugs and these kinds of things. You hear all the time about celebrities dying because they combined alcohol with barbituits. Is there any evidence that the size that occur during sleep or during states of deep, deep relaxation and sedation that size recover the brain? Because you could imagine that if the size don't happen as

Starting point is 00:50:27 a consequence of some drug impacting these brain centers, that that could be one cause of basically asphyxiation and death. If you look at the progression of any mammal to death, you find that their breathing slows down, a death due to quote, natural causes. Their breathing slows down. It's, we'll stop and then they'll gasp. So we have the phrase dying gas, the super large breaths. They're often described as an attempt to order or resuscitate. That is, you take that super deep breath and that

Starting point is 00:51:09 maybe it can kickstart the engine again. We do not know the degree to such things as gasp are really size that are particularly large. And so if you suppress the ability to gasp in an individual who is a subject to an overdose, then whereas they might have been able to re-arouse their breathing, if that's prevented, they don't get re-aroused. So that is certainly a possibility. But this has not been investigated. I mean, one of the things that interested in is in individuals who have diseases which

Starting point is 00:51:56 will affect pre-buttzing of complex. And there's data in Parkinson's disease and multiple system atrophy, which is another form of neurodegeneration, where there's loss of neurons in prebuttsinger. And the question is, and it also may happen in ALS, sometimes you'll find there was no garricks disease, an mitchofer cladroscarosis. These individuals often die during sleep. We have an idea that we have not been able to get anyone to test is that patients would Parkinson's, patients with MLS, typically breathe normally during wakefulness.

Starting point is 00:52:48 The disturbances that they have in breathing is during sleep. So Parkinson's patients at the end stages of the disease often have significant disturbances in their sleep pattern, but not during wakefulness. And we think that what could be happening is that the proximate cause of death is not heart failure is that they become apneic, they stop breathing and don't resuscitate. And that resuscitation may or may not be due to an explicit suppression of size, but to an overall suppression of the whole apparatus of the pre-butts in a complex. Got it. Thank you. So, Yakko calls you out. So, he calls me up and he's great kids, super smart,

Starting point is 00:53:36 and he tells me about these experiments that he's doing. We are keys looking at a database that he's doing, we are a key's looking at a database to try and find out what molecules are enriched in regions of the brain that are critical for breathing. So we and others have mapped out these regions in the brain stem, and he was looking at one of these databases to see what's enriched. And I said, that's great. We'd be willing to sort of share work together. He says, no, my advisor doesn't want me to do that. So I said, OK.

Starting point is 00:54:12 But Kevin's a great kid. And I enjoyed talking to him. And he's a smart guy. And, you know, what I found in academia and is that the smartest people only want to hire people smarter than them, and only want to have the preference to interact with people smarter than them.

Starting point is 00:54:36 The faculty who are not at the highest level and at every institution, there's a distribution. There are ones above the mean and those below the mean. Those who below the mean are very threatened by that. And I saw Kevin as like a shining light and I didn't care whether he was gonna out compete me because whatever he did was gonna help me in the field. So I did wherever I can't help it,

Starting point is 00:55:03 to work with Kevin. So at one point, I got invited to give grand rounds in neurology at Stanford. Turns out an undergraduate student who had worked with me was now headed a training program for neurologist at Stanford and he invited me. And at the end of my visit, I go to Mark Krausner's office, and Kevin is there, and a postdoc pungly who was also working on a project was there. And towards the end of the conversation, Mark says to me, you know, we found this one molecule which is highly concentrated in an important region for breathing. And he said, oh, that's great.

Starting point is 00:55:52 What is it? And he says, I can't tell you because we want to work on it. So of course, I'm disappointed, but I realized that the ethic in some areas of science or the custom in some areas of science is that until you get a publication, you'll be relatively strict and sharing the environment. I can have a chat when I came back. Well, he may remember the story differently, but I said, okay, and as I'm walking out the door, I remember these experiments I described to you about

Starting point is 00:56:26 Bombasin and that was the only unusual molecule we're working in. So the reason I'm rushing out the doors, I have a flight to catch. So I stick my head in, I said, is this molecule related to Bombasin? Then I run off, I don't even wait for them to reply. I get to pee up for it. Mark calls me and he says, bombison, the peptide we found is related to bombison.

Starting point is 00:56:51 What does it do? And I said, I'm not telling. And I'm so glad I wasn't involved in this collaboration. No, no, but that was sort of a tease because I said, well, let's work together on this. And then we work together on this. The prisoners dilemma at that point. Yeah. So Kevin Yackel is spectacular, has his own lab at UCSF, and the work that I'm familiar with from Kevin is worth mentioning now, or I'll ask you to mention it, which is this reciprocal

Starting point is 00:57:27 relationship between brain state, or we could even say emotional state and breathing. And I'd love to get your thoughts on how breathing interacts with other things in the brain. You've beautifully described how breathing controls the lungs, the diaphragm, and the interactions between oxygen and carbon dioxide and so forth. But as we know, when we get stressed, our breathing changes, when we're happy and relaxed, our breathing changes. But also, if we change our breathing, we, in some sense, can adjust our internal state. What is the relationship between brain state and breathing? And if you would, because I know you have a particular love of one particular aspect of this, what is the relationship

Starting point is 00:58:14 between brain rhythms, oscillations, if you will, and breathing? This is a topic which has really intrigued me over the past decade. I would say before that, I was in my silo, just interested about how the rhythm of breathing is generated, and they really pay much attention to this other stuff. For some reason, I got interested in it. And I think it was triggered by an article in the New York Times about mindfulness.

Starting point is 00:58:42 Now, believe it or not, although I'd lived in California for 20 years at that time, I never heard a mindfulness. It's staggering how isolated you can be from the real world. And I googled it, and there was a mindfulness institute at UCLA, and they were giving courses in meditation. So I said, oh, this is great, because I can now see whether or not the breathing part of meditation has anything to do with the purported effects of meditation.

Starting point is 00:59:12 So I signed up for the course. And as I joked to you before, I had two goals. One was to see whether or not breathing had an effect. And the other was to levitate because I grew up with all these kung-fu things, and all the monks could levitate when they meditated. So why not? You know, we have a mile in the lab. You can't do anything interesting if you're afraid of failing. And if I fail to levitate, well, at least I try. And I should tell you now, I still haven't done it yet, but I haven't given up yet. I haven't given up. I should tell you now I still haven't done it yet, but I haven't given up yet.

Starting point is 00:59:43 I haven't given up. So I took this course in mindfulness and it became apparent to me that the breathing part was actually critical. It wasn't simply a distraction or a focus. It, you know, they could have had you move your index finger to the same effect, but I really believe that the breathing pot was involved. Now, I'm not an unbiased observer,

Starting point is 01:00:11 so the question is, how can I demonstrate that? I didn't feel competent to do experiments in humans, and I didn't feel like I designed the right experiments in humans, but I felt maybe I can study this in rodents. So we got this idea that we're going to teach rodents to meditate. And you know, that's laughable. But we said, but if we can, then we can actually study how this happens. So believe it or not, I was able to get a sort of a stardag grant, a not 21 from NCCH. That's the national complimentary medicine.

Starting point is 01:00:57 A wonderful institute I should mention. Our government puts major tax dollars toward studies of things like meditation, breathwork, supplements, herbs, acupuncture. This is, I think, not well known, and it's an incredible thing that our government does that, and I think it deserves a nod and more funding. I totally agree with you. I think that it's the kind of thing that many of us, including many scientists, think is to woo-woo and unsubstantiated. But learning more and more, you know, we used to laugh at neuroimmunology that the nervous

Starting point is 01:01:36 system did have anything to do with the immune system. And paying itself can influence your immune system. I mean, there are all these things that we're learning that we used to dismiss. And I think there's real nuggets to be learned here. So they were not in the women, they funded this particular project. And now I'm gonna leap ahead because for three years,

Starting point is 01:02:00 we threw stuff up against the wall that didn't work. And recently, we had a major breakthrough. We found a protocol by which we can get mice to breathe slowly, or wake mice to breathe slowly. I won't tell you. Normally, they don't breathe slowly. No, no, no. In other words, whatever the normal breath is,

Starting point is 01:02:24 we could slow it down by a factor of 10, and they're fine doing that. So we could do that for, we did that 30 minutes a day for four weeks, okay, like a breath practice. Do they levitate? We haven't measured that yet. I would say, A-PARR, we haven't seen them floating to the top of their cage, but we haven't weighed them.

Starting point is 01:02:47 Maybe they weigh less. Maybe levitation is graded. And so maybe if you weigh less, it's sort of partial levitation. In any case, we then tested them. And we had control animals, mice, or we did everything the same, except the manipulation we made did not slow down their breathing. So but they went through everything else. We then put them to a standard fear conditioning, which we did with my colleague Michael Fanzelow,

Starting point is 01:03:21 who's one of the real gurus of fear. And we measured a standard test is to put mycena condition where they're concerned that we see a shock and their responses that they freeze. And the measure of how fearful they are is how long they freeze. This is well validated, and it's way above my pay rate, they describe the validity of the test, but it's very valid. The control mice had a freezing time, which was just the same as what Nuri mice would have. The ones that went through our protocol froze much, much less.

Starting point is 01:04:08 According to Michael, the degree to which they showed less freezing was as if there was a major manipulation in the amygdala, which is a part of the brain that's important in fear processing. It's a staggering change. What we have now is the grant rate out of money, the post-op working limit left, and now we have to train piece together everything,

Starting point is 01:04:33 and but the data is spectacular. Well, I think it's, I'll just pause you for a moment there, because I think that the, you know, you're talking about a rodent study, but I think the benefits of doing rodent studies that you can get deep into mechanism and for people that might think, well, we've known that meditation has these benefits. Why do you need to get mechanistic science? I think that one thing that's important for people to remember is that, first of all, as many people as one might think are meditating out there or doing breathwork,

Starting point is 01:05:06 a far, far, far greater number of people are not. Right? I mean, there's a... The majority of people don't take any time to do dedicated breathwork nor meditate. So whatever can incentivize people would be wonderful. But the other thing is that it's never really been clear to me just how much meditation is required for a real effect, meaning a practical effect. People say 30 minutes a day, 20 minutes a day, once a week, twice a week, same thing with breath work.

Starting point is 01:05:36 Finding minimum or effective thresholds for changing neural circuitry is what, I think, is the holy grail of all these practices. And that's only going to be determined by the sorts of mechanistic studies that you describe. So this is wonderful. I do hope the work gets completed. And we can talk about ways that we can ensure that that happens. But let me add one thing to what you're saying, Andrew.

Starting point is 01:06:00 One of the issues, I think, for a lot of people is that there's a placebo effect. That is in humans, they can respond to something even though the mechanism has nothing to do with what the intervention is. And so it's easy to say that the meditative responses has a big component which is a placebo effect. My mice don't believe in the placebo effect. And so if we could show this a bona fide effect in mice,

Starting point is 01:06:29 it is convincing in ways that no matter how many human experiments you did, the control for the placebo effect is extremely difficult in humans. It mice, it's a non-issue. So I think that that in and of itself would be a enormous message to send. Excellent. And indeed a better point. I think a 30-minute-a-day meditation in these mice, if I understand correctly, the meditation, we don't know what they're thinking about.

Starting point is 01:06:59 It's breath practice. Right. So it's breath practice. So because we don't, they're presumably they're not thinking about their third eye center, lotus position, levitation, whatever it is. They're not instructed as to what to do. And if they were, they probably wouldn't do it anyway. So 30 minutes a day in which breathing is deliberately slowed or is slowed relative to their normal patterns of breathing, got it.

Starting point is 01:07:22 What was the frequency of sign during that 30 minutes? I don't know yet. Well, no, we have the data. We're analyzing the data to be determined or to be announced at some point. So the fear centers are altered in some way that creates a shorter fear response to a foot shock. Right.

Starting point is 01:07:43 What are some other examples that you are aware of from work in your laboratory or work in other laboratories for that matter about interactions between breathing and brain state or emotional state? So, this gets back to our prior conversation. I sort of went off in that tangent. We need, I think we need to think separately of the effect of volitional changes of breathing on emotion versus the effect of brain state on breathing. So the effect of brains that are breathing like when you're stressed is an

Starting point is 01:08:24 effect, presumably originating in higher centers, if I can use that term, affecting breathing. It's, the reciprocal is that when you change breathing, it affects your emotional state. I think, I think of those two things as different than they ultimately be tied together. So there's a landmark paper published in the 50s where they stimulated in the amygdala of cats and depending on where they stimulated, they got profound changes in breathing. There's like every pattern of breathing

Starting point is 01:08:58 that possibly imagined they found a site in the amygdala which could produce that. So there's clearly a powerful descending effect coming from the amygdala, which could produce that. So this clearly, a powerful descending effect coming from the amygdala, which is a major site for processing emotion, fear, stress, and whatnot, that can affect breathing. And clearly, we have volitional control over breathing. So we have profound effects there. Now, I should say about emotional control

Starting point is 01:09:22 of breathing. I need to segue into talking about locked-in syndrome. Locked-in syndrome is a devastating lesion that happens in a part of the brainstem, where signals that control muscles are transmitted. So the fiber is coming from your motor cortex, go down to this part of the brain stem, which is called the ventral ponds. And if there's a stroke there, it can damage these pathways. What happens in individuals who have locked in syndrome is they lose all volitional movement

Starting point is 01:10:02 except lateral movement of the eyes and maybe the ability to blink. The reason they're able to still blink and move their eyes is that those control centers are not interrupted. In other words, the interruption is below that. They continue to breathe because the sentence for breathing don't require that volitional command. In any case, they're below that, so they're fine. So these people continue to breathe normal intelligence, but they can't move.

Starting point is 01:10:40 There's a great book called The Diving Bell in the Butterfly about a young man Who had this happens to and he describes his life and it's a real testament to human The human condition that he does this. It's a remarkable book. It's a short book Did you write the book by blinking? He wrote it later. He did it by blinking to his caretaker He did it by blinking to his caretaker. It's pretty amazing. And there was a movie which I've never seen with Javier Bardin as the protagonist, but the book I highly recommend is to anyone to read.

Starting point is 01:11:17 So I colleagues studying an individual I'd locked in syndrome. And this patient breathed very robotically, totally consistent, very regular. They gave the patient a low oxygen mixture to breathe. Ventilation went up. A CO2 mixture to breathe ventilation went up. So all the regulatory apparatus for breathing was there. They asked the patient to hold his breath or to breathe faster.

Starting point is 01:11:44 Nothing happened. Just the patient recognized the command, but couldn't change it. And all of a sudden the patient's breathing changed considerably, and they said that the patient would happen. They said, you told the joke and I left. And they went back, whenever they told the joke that the patient found funny, the patient's breathing pattern changed. And you know your breathing pattern when you laugh is, you know, inhale, you go, ha, ha,

Starting point is 01:12:13 ha, ha, ha. But it's also very distinctive. We have some neuroscience colleagues who will go unnamed, who if you heard them laugh 50 yards away, you know exactly who they are. Yeah, well, I'll name him Eric Kendell. For one. Has an inspiratory laugh. Yeah.

Starting point is 01:12:29 He's famous for a, as opposed to a, huh? Exactly. Yeah, exactly. So, it's very stereotyped, but it's maintained and these people lose volitional control of breathing. So there's an automotive component controlling your breathing, which has nothing to do with your volitional control, and it goes down to a different pathway, because it's not disrupted by this locked-in syndrome. If you look at motor control of the face, we have the volitional

Starting point is 01:12:59 control of the face, but we also have emotional control of the face, which most of us can't control. So when we look at another person, we're able to read a lot about what their emotional state is, and that's a lot about how primates communicate, humans communicate. And you have people who are good deceivers, probably used car salesmen, poker players, or now poker players have tells, but many of them now wear dock glasses because a lot of the tells you blink or whatnot.

Starting point is 01:13:35 Pupil sizes. Pupil sizes, Pupil sizes to tell, which is an autonomic function, not a skeletal muscle function, but we have these all these skeletal muscles which we're controlling, which give us away. I have tried to get my imaging friends to image some of the great actors that we have in Los Angeles. Brain images. Brain images.

Starting point is 01:14:01 I'm sorry. No, that's right. I mean, I get brain images. I'm sorry. No, that's right. I mean, I get brain images because I think when I tell you to smile, I could tell that you're not happy, that you're smiling because I ask you to smile. I think I hear about to crack a joke, but we're old friends. So, no, when you see a picture, like at a birthday, I want none and say, say cheese, you know, when you see a picture, like at a birthday or whatnot, and say, say cheese, you could tell that at least half of the people are not happy to saying cheese.

Starting point is 01:14:32 Whereas a great actor, when they're able to disemble and the fact that they're sad or they're happy, you believe it, they're not faking it. It's like that's great acting. And I don't think everyone could do that. I think that the individuals who are able to do that have some connection to the plots of their amount of control system that the rest of us don't have.

Starting point is 01:14:56 Maybe they develop it through training, and maybe not, but I think that this can be image. So I would like to get one of these great actors in a imager and have them go through that and then get a normal person and see whether or not they can emulate that. And I think you're going to find big differences in the way that control this emotive thing.

Starting point is 01:15:16 So there's a mode of control, the facial muscles. I think it's in large part similar to the emotive control of breathing. So there's that emot of control, and there's that volitional control, and they're different. They're different. Now, you asked me about the Yakkhal stuff. The Yakkhal paper had to do with ascending

Starting point is 01:15:39 that they affect the breathing on emotion. What Kevin found was that there was a population of neurons in the pre-buttzing of complex that were always looking to things that are projecting ultimately a motor neurons. He found the population of cells that projected to locus surrealists. Mocasurius, excuse me, is one of those places in the brain that seem to go everywhere. It's a sprinkler system, exactly. And influence, mood, and you've had podcasts about this. I mean, there's a lot of stuff going on with the Amoeba.

Starting point is 01:16:15 So I'll send you the Locust Rilius. So you get into the Locust Rilius, you can now spray information out throughout the entire brain. He found specific cells that projected from prebuttsinger to locus cerulias, and that these cells are inspiratory modulator. Now, it's been known for a long time, since the 60s, that if you look in the locus cerulias of cats when they're awake, you find many neurons that have respiratory modulation. No one paid much attention to him. Why bother? Not why bother paying attention, but why would the brain bother to have these inputs? So what Kevin did with

Starting point is 01:17:05 with Lindsey Schwartz and Lee-Lysian Lozlaya, is they killed, oblated, those cells going to Locustarius from Prebatsigar. And the animals became calmer. And their EEG levels changed in ways they're indicative that they became calmer. And as I recall, they didn't just become calmer, but they weren't really capable of higher-ousal states. They were kind of flat.

Starting point is 01:17:29 I don't think we really pursue that in the paper. And so we'd have to ask Johnny Huginard about that, but I think he's on the other side of my lap. So we'll ask him. But nonetheless, He's on the other side of my lap, so we'll ask him. But nonetheless, that beautifully illustrates how there's a bi-directional control, right? Well, that's emotion. Emotion, well, no, the two stories of the locked-in syndrome plus the yak ol' paper shows

Starting point is 01:18:02 that emotional states influence breathing and breathing influences emotional states, which, but you mentioned inspiration, which I always call inhalation, but people will follow. No, that's fine. Those are interchangeable. People can follow that. There's some interesting papers from Nome Sobles group and from a number of other groups that as we inhale or right after we inhale, the brain is actually more alert

Starting point is 01:18:26 and capable of storing information than during exhales, which I find incredible, but it also makes sense. I'm able to see things far better when my eyes are open than when my eyelids are closed for that matter. Maybe. I mean, I don't doubt, I mean, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, no, least, well, there are several other sites. And let me sort of go through that. One is olfaction. So when you're breathing, normal breathing, you're inhaling and exhaling.

Starting point is 01:19:15 This is creating signals coming from the nasal mucosa that is going back into the olfactory bulb. That's respiratory modulated. And the olfactory bulb has profound influence and projections to many parts of the brain. So there's a signal arising from this ridlic moving of air in and out of the nose that's going into the brain that has contained an irrespectory modulation. So that signal is there. The brain doesn't have to be using it, but when it's discriminating over and whatnot,

Starting point is 01:19:50 that's riding on a oscillation, which is respiratory related. Another potential source is the Vegas nerve. The Vegas nerve is a major nerve, which is containing aphorense from all of the viscera. Afference just being a signal. A signal. A signal too.

Starting point is 01:20:09 A signal is from the viscera. It also has signals coming from the brainstem down, which are called ephrens, but it's getting major signals from the lung, from the gut, and this is going up into the brainstem. So it's there. There are very powerful receptors in the lung that are responding to the lung volume,

Starting point is 01:20:32 the lung stretch. They're barrel receptors. Sorry, that, well, we have a number of, like the piezo receptors of this year's Nobel Prize, yeah. So they're responding to the expansion and relaxation in the lung. And so if you record from the Vegas nerve, you'll see that there's a huge respiratory modulation

Starting point is 01:20:54 due to the mechanical changes in the lung. Now, why that is of interest is that for some forms of refractory depression, electoral stimulation of the vagus nerve can provide tremendous relief. Why this is the case still remains to be determined, but it's clear that signals in the vagus nerve, at least artificial signals in the vagus nerve,

Starting point is 01:21:20 can have a positive effect on reducing depression. So it's not a leap to think that under normal circumstances that that rhythm coming in from the Vegas nerve is playing a role in normal processing. Okay, let me continue. Come to Oxide in oxygen levels. Now under normal circumstances, your oxygen levels are fine.

Starting point is 01:21:46 And unless you go to altitude, they don't really change very much. But your CO2 levels can change quite a bit with even a relatively small change in your overall breathing. That's gonna change your pH level. Have a colleague, Alicia Morett, who has working with patients who have, who are anxious, and many of them hyperventilate. And as a result of that hyperventilation,

Starting point is 01:22:15 there come dioxide levels low. And she has developed a therapeutic treatment She has developed a therapeutic treatment where she trains these people to breed slower and to restore their CO2 levels back to normal and she gets relief in their anxiety. So CO2 levels, which are not going to affect brain function on a breath by breath level, although it does fluctuate breath by breath, but it's sort of a continuous background, can change. And if it's changed chronically, we know that highly elevated levels of CO2 can produce panic attacks. And we don't know the degree to that, so it gets exacerbated by people who have a panic attack.

Starting point is 01:23:07 It's a degree to which their ambiance CO2 levels are affecting their degree of discomfort. What about people who tend to be too calm, meaning they're feeling sleepy, they're underbreeding as opposed to overbreeding? Is there any knowledge of what the status of CO2 is in their system? I don't know, which doesn't mean there's no knowledge, but I'm unaware. I'm unaware, but that's blissfully unaware. I've not looked at that literature, so I don't know.

Starting point is 01:23:39 And I mean, most people, excuse me, most of the scientific literature around breathing in humans that I'm aware of relates to these stressed states because they're a little bit easier to study in the lab, whereas people feeling understimulated or exhausted all the time, it's a complicated thing to measure. I mean, you can do it, but it's not as straightforward.

Starting point is 01:23:57 Well, CO2 is easy to measure. But in terms of the sort of, the measures for feeling fatigue, you know, they're somewhat indirect, where I stress who we can get at pulse rates in HRV and things that sort of. Well, I imagine that these devices that we're all wearing will soon be able to measure. Well, not like a measure, oxygen levels,

Starting point is 01:24:16 oxygen saturation. Just amazing. Yeah. But, oxygen, you know, pretty much stay about 90% unless there's some pathology where you go to altitude. But CO2 levels vary quite a bit. And CO2, in fact, because their very, your body is so sensitive, the control of breathing, like how much you breathe per minute, is determined in a very sensitive way by the CO2 level.

Starting point is 01:24:45 So even a small change in your CO2 will have a significant effect on your ventilation. So this is another thing that now changes your ventilation but affects your brain state. Now another thing that could affect breathing practice, can affect your emotional state is simply the descending command. Because breathing practice involves volitional control of your breathing. Therefore, this is signal that's originating somewhere in your motor cortex. That is not, of course,

Starting point is 01:25:19 that's going to go down to prebuttsinger, but it's also going to send off collaterals to other places. Those collaterals could obviously influence your emotional state. So we have quite a few different potential sources. None of them are exclusive. There's an interesting paper which shows that if you block nasal breathing, you still see breathing-related oscillations in the brain. And this is where I think the mechanism is occurring, is that these breathing-related oscillations in the brain, they are playing a role in signal processing.

Starting point is 01:26:00 And maybe it should, I talk a little bit about the role that oscillations may be playing in signal processing. And maybe it should I talk a little bit about the role that oscillations may be playing in single process? Definitely, but before you do, I just want to ask you an intermediate question. We've talked a lot about inhalation, inspiration, and exhalation. What about breath holds? You know, in apnea, for instance, people are holding their breath, whether or not it's conscious or unconscious, they're holding their breath. What's known about breath holds in terms of how it might interact with brain state or oxygen

Starting point is 01:26:32 CO2? And I'm particularly interested in how breath holds with lungs empty versus breath holds with lungs full might differ in terms of their impact on the brain. I'm not aware of any studies on this, looking at a mechanistic level, but I find it really interesting. And even if there are no studies, I'd love it if you cared to speculate. Well, one of the breath practices that intrigued me is where you basically hype eventolate for a minute and then hold your breath for as long as you can.

Starting point is 01:27:01 Tumo style, Wim off style. We call it in the laboratory because, frankly, before Tumor and before Wim, it was referred to as cyclic hyperventilation. So it was basically followed by a breath hold and that breath hold could be done with lungs fall or lungs empty. So I had a long talk with some colleagues about what they might think the underlying mechanisms are, particularly for the breathhold. And, there's certainly, I certainly envision that there's a component with respect to the

Starting point is 01:27:38 presence or absence of that ridnessity in your cortex, which is having effect. But the other thing with the hyperventilation, hyperventilation, or the apnea, is your CO2 levels are going from low to high. Any time you're holding your breath. Any time you're holding your breath, okay? And those are gonna have a profound influence. Now, I have to talk about episodic hypoxia, because there's a lot of work going on, particularly with Gordon Mitchell, the University of Florida,

Starting point is 01:28:11 doing some extraordinary work on episodic hypoxia. So in the 80s, David Milhorn did some really intriguing work. If I ask you to hold your breath, excuse me, if I gave you a low oxygen mixture for a couple of minutes, your breathing level would go up. Of course, you wouldn't, you want to have more oxygen. You started your air. Yeah. No, you're still in for oxygen, right?

Starting point is 01:28:39 OK. And for a couple of minutes, you go up, you can reach some steady state level. Not so hypoxic that you can't reach an equilibrium. And then I give you room mayor again, the ventilation quickly relaxes back down to normal. If on the other hand, I gave you three minutes of hypoxia, five minutes of normal oxygen,

Starting point is 01:29:04 three minutes of hypoxia, five minutes of normal oxygen, three minutes of hypoxia, five minutes of normal oxygen, three minutes of hypoxia, five minutes of normal oxygen. Normal oxygen. Normal air. Your ventilation goes up, down, up, down, up, down, up. After the last episode, your breathing comes down and doesn't continue to come down, but rises again and stays up for hours. Okay? This is well validated now. This was originally done in Amazon and humans all the

Starting point is 01:29:32 time. It seems to have profound benefit on motor function and cognitive function in what direction? Positive. Positive. I've often toyed with the idea of getting a 5%, an 8% oxygen, don't do this, listen to this. Getting an 8% oxygen tank by my desk when I'm writing a grant and doing like a blue velvet and going through the episodic hypoxia to improve my cognitive function. Because certainly I could use improvement

Starting point is 01:30:03 when I'm writing grants. But you could do this without the low oxygen. I mean, you could do this through breath work, presumably. It's hard to lower your oxygen enough. OK. We're going in the experimental studies. They typically use 8% oxygen. It's hard to hold your breath long enough.

Starting point is 01:30:21 And there is another difference here. That is, what's happening to your CO2 levels. When you hold your breath, your oxygen levels are dropping, your CO2 levels are going up. When you're doing episodic hypoxia, your CO2 levels are going to stay pretty normal. Of course, you're still breathing. It's just the oxygen levels are gone. So unlike normal conditions, which you described before, where oxygen is relatively constant, and CO2 is fluctuating depending on emotional state

Starting point is 01:30:54 and activity and things of that sort. In episodic hypoxia, CO2 is relatively constant, but you're varying the oxygen level coming into the system quite a bit. I would say it's relatively, I would say CO2 is relatively constant, but it's not going to go in a direction which is going to be significantly far from normal. Whereas when you're holding your breath, you're going to become both hypoxic and hypercaptic at the same time. We should explain to people what hypoxic and hyperpocaptin are. Because we have it. Hypoxic is just a technical term for low levels of oxygen.

Starting point is 01:31:27 Hyper or you could say hypoxic, low. Hyper is high. So hyperoxia or hypocaptin low CO2 or hypercaptin your high levels of CO2. So when you're in episodic hypoxia, if anything, you're going to become hypocaptic, not hypercaptic. And that could play an influence on this. One example that I remember in Gordon will have to forgive me if I'm misquoting this,

Starting point is 01:31:58 is they had a patient who had a stroke and had weakness in ankle flexion. That is, it's just me ankle extension to extend the ankle. And so they had the patient in the seat with a measure ankle extension. And then they measured it. And then they exposed the patient to episodic hypoxia and they measure it again the strength of the ankle extension one way up and so Gordon is looking at this they're looking at this now for spinal cord rehab and I imagine for all sorts of neuromuscular performance it could be beneficial Gordon is looking

Starting point is 01:32:42 in athletic performance we have a project which we haven't been able to push to the next level, to do golf. So I think my golf. Because you love golf. Well, it's because it's motor performance, coordination. So it's not simply running as fast as you can. It's coordination, it's concentration. It's a whole variety of things.

Starting point is 01:33:04 And so the idea would be to get a group of golfers and give them their placebo control. So they don't know whether they're breathing a gas mixture, which is just normal air, where Ipoxic gas mixture, although they may be able to figure it out based on their response. Do it on the control circumstances that do it into a net, measure their blanket, their drives, their dispersion and whatnot, and see what happens. Look, if we could find that this works for golfers, forget about cognitive function, we could sell this for unbelievable amounts of money. That sounds like a terrible idea. By the way, I'm not serious about selling

Starting point is 01:33:47 it, but I know you're joking. I think maybe people should know that you are joking about that. No, I think that anything that can improve cognitive and neuromuscular performance is going to be of interest for a wide range of both pathologic states, like injury, TBI, et cetera. I mean, one of the most frequent questions I get is about recovery from concussion or traumatic brain injury. A lot of people think sports. They think football, they think rugby, they think hockey. But if you look at the statistics on traumatic brain injury, most of it is construction workers, car crashes,

Starting point is 01:34:19 bicycle accidents. I mean, the sports part of it is a tiny, tiny, minuscule fraction of the total amount of traumatic brain injury out there. I think these protocols tested in the context of golf would be very interesting because of the constraints of the measures, as you mentioned, and it could be exported to a number of things.

Starting point is 01:34:37 I want to just try and imagine whether or not there is any kind of breathing patterned or breath work just to be direct about it, that even partially mimics what you described in terms of episodic hypoxia. I've done a lot of tumor, Wimhoff, cyclic hyperventilation type breathing before. My lab studies this in humans and what we find is that if people do cyclic hyperventilation,

Starting point is 01:35:02 so for about a minute, then exhale, hold their breath for 15 to 60 seconds, depending on what they can do, and just keep repeating that for about five minutes. It seems to me that it, at least partially mimics the state that you're talking about, because afterwards, people report heightened levels of alertness, lower levels of kind of triggering

Starting point is 01:35:24 due to stressful events. they feel comfortable at a higher level of autonomic arousal, cognitive focus, a number of improvements that are pretty impressive that any practitioner of Wimhoff or Tuma will be familiar with. Is that pattern of breathing even, can we say that it maps to what you're describing in some general sense? Well, the expert in this would be Gordon Mitchell. I would say it moves in that direction, but it's not as extreme because I don't think you can get down to the levels of hypoxia that they do clinically. I know that our pals at our breath collective actually just bought a machine because you buy a machine that does this.

Starting point is 01:36:07 I see. And they bought it and they're going to do their own self-testing to see whether or not this has any effect on anything that they can measure. Of course, you have to be concerned about self-experimentation, but I applaud their curiosity in going after it. Hyperbaric chambers. I hear a lot nowadays about hyperbaric chambers. People are buying, I'm in using them.

Starting point is 01:36:28 And what are your thoughts on hyperbaric chambers as it relates to any of the hyperbaric chambers? Hyper or hyperbaric chambers? Hyperbaric chambers. So you're not talking about altitude? No. I don't really have much to say. I mean, your auction levels will probably go up a little bit.

Starting point is 01:36:44 And that could have a beneficial effect, but that's way outside my area of comfort. I think 2022, I think, is going to be the year of two things I keep hearing a lot about, which is the deliberate use of high salt intake for performance, blood increasing blood volume, et cetera, and hyperbaric chambers seem to be catching on much in the same way that ice baths were in and

Starting point is 01:37:05 sauna seem to be right now. But anyway, a prediction we can return to at some point. I want to ask you about some of the studies that I've seen out there exploring how deliberately restricting one's breathing to nasal breathing can do things like improve memory. There's a couple papers in Journal of Neuroscience, which is a respectable journal in our field. One, looking at olfactory memory, so that kind of made sense because you can smell things better through your nose than your mouth, unless you're some sort of, you know, elk or something where they can, presumably they have some sense of smell in their mouth as well. But humans generally smell what their nose. That wasn't terribly surprising, but there was a companion study that showed that the hippocampus

Starting point is 01:37:50 and area involved in encoding memories in one form or another was more active, if you will, and memory and recall was better when people learned information while nasal breathing as opposed to mouth breathing. Does that make sense from any mechanistic perspective? Well, given that there's a major pathway going from the olfactory system into the brain, and you cut that, and not one, from any receptors in the mouth,

Starting point is 01:38:22 the degree of respiratory modulation you're going to see throughout the forebrain is going to be less with mouth breathing than nose breathing. So it's certainly plausible. I think there are a lot of experiments that need to be done to distinguish between the two that is the nasal component and the non-nazal component of these breathing related signals. There's a tendency sometimes when you have a strong effect to be exclusive. And I think what's going on here is that there are many inputs that can have an effect. Now, whether they're puzzled that some effect, this part of behavior and some effect, that part of behavior remains to be investigated.

Starting point is 01:39:18 There's certainly a strong olfactory component. My interest is trying to follow the central component because we know that there's a strong central component in this. In fact, there's a strong central projection to the olfactory bulb. So regardless of whether or not there's any in and out of the nose, there's a respiratory input into the olfactory bulb, which combines with the respiratory modulated signals coming from the sensory receptors. Interesting. And as long as we are poking around, forgive the pun, the nose, what about one nostril versus the other nostril? I know it sounds a little crazy to imagine, but there have been

Starting point is 01:40:00 theories in yoga traditions and others that breathing through one nostril somehow activates certain brain centers, maybe hemispherically one side of the brain versus the other or that right nostril and left nostril breathing might differ in terms of the levels of alertness or calmness they produce. I'm not aware of any mechanistic data on that, but if there's anything worthwhile, right nostril versus left nostril breathing that you're aware of, Iistic data on that, but there's anything worthwhile out right in Austral versus left-N Austral breathing that you're aware of, I'd love to know. Well, it's certainly plausible. I don't know of any data demonstrating it except the anecdotal reports. As you know, the brain is highly lateralized and we have speech on one side and a dominant hand on one side. And so the

Starting point is 01:40:48 notion that if you have this huge signal coming from the olfactory system, and the some degree it's centralized is not perfectly symmetrical, that is one side is not going evenly to both sides, then you can imagine. And once the signal gets distributed in a way that's not uniform, that the effectiveness or the response is going to be particular to the cortex in which either the signal still remains or the signal is removed from. I see. What are some of the other features of our brain and body, be it blinking or eye movements or ability to encode sounds, or any features of the way that we function and move and perceive things that

Starting point is 01:41:42 are coordinated with breathing in some interesting way. Thank you for that question. Almost everything. So we have, for example, on the autonomic side, we have respiratory sinus arrhythmia, that is during expiration, the heart slows down. Your pupils oscillate with the respiratory cycle. I don't know what the functional basis for that is,

Starting point is 01:42:09 but they do oscillate with the respiratory cycle. When we inhale our pupils constrict presumably, because there's an increase in heart rate and sympathetic tone, I would think of constriction. I'm guessing as you relax, the pupil will get and you exhale. I take you right, but I always get, you know, I always get the valence of that.

Starting point is 01:42:26 Well, it's counterintuitive because people wouldn't think that when the pupils get, I mean, it depends. I mean, you can get very alert and aroused in that for stress or for good reasons. And the pupils get wider, but your visual field narrows, and then the opposite is true. Anyway, I guess the idea is that the pupils are changing size and therefore the aperture your visual window is changing in coordination with breathing.

Starting point is 01:42:51 Your fear response changes with the respiratory cycle. Tell us more about that. Well, it's a paper by Zolano, which I think showed rather clearly that if you show individuals fearful faces that they're measured response of fearfulness changes between inspiration and I don't know why, but it does. Your reaction time changes. So you talk about blinking. The reaction time changes between inspiration and expression. If I ask you to punch something, that time will change between inspiration and expression. In fact, I don't know the degree to which martial artists

Starting point is 01:43:43 exploit that. You watch the breathing pattern, and your opponent will actually move slower during one cycle compared to the other. Meaning in which direction, if they're exhaling, they can punch faster. I have to say, I don't keep a table of which direction things move in because I'm out of the martial arts field. My vague understanding is that exhales on strikes is the more typical way to do that. So as people strike, they exhale.

Starting point is 01:44:19 In many respects. As you exhale, but there are other components to strike and because you want to stiffen your rib cage, you want to make a Valsalva manoeuvre. So that's both an inspiration and an expiration at the same time. So I don't know enough about when you say during expiration, I would assume that when you make your strike,

Starting point is 01:44:43 you actually sort of want to stiffen here, which is a valve salve of like maneuver. And oftentimes they'll clinch their fist at the last moment. Because anyway, there's a whole set of motor things that we should, we can talk to some fighters. We know people who know fighters. So we can ask them, interesting, what are some other things that are modulated by breathing?

Starting point is 01:45:03 some other things that are modulated by breathing. I think anything anyone looks at seems to have a breathing component because it's all over your brain. And it's hard to imagine it not being effective. Now, whether it's incidental or just background and doesn't really have any behavioral advantage is possible. In other cases, there might have a behavioral advantage. I mean, the big, this eye opening thing for me, probably a decade ago, was digging into literature and seeing how much of core collectivity and subcore collectivity

Starting point is 01:45:49 had a respiratory modulated component to it. And I think a lot of my colleagues who are studying cortex are oblivious to this. And they find, I heard it talk the other day, the person who go on name, who find a lot of things correlated with a particular movement. And I think, when I looked, I said, gee, that's a list of things that are respiratory modulated, and rather than it being correlated to the movement that we're looking at,

Starting point is 01:46:22 I think the movement they were looking at was modulated by breathing as was everything else. So there wasn't that the movement they were looking at, I think the movement they were looking at was modulated by breathing as was everything else. So there wasn't that the movement itself was driving that correlation, it was that they were all correlated to something else, which is the breathing movement. And whether or not that is a behaviorally relevant or behaviorally something you can exploit, I don't know.

Starting point is 01:46:43 I suspect you're right. That breathing is, if not the foundational driver of many, if not all of these things, that it's at least one of the foundations. It's in the background, it's in the brain, and oscillations play an important part in brain function. And they vary in frequency from maybe 100 hertz down

Starting point is 01:47:08 to what we can get to circadian and sort of monthly cycles. But breathing occupies a rather unusual place and all that. Because so let me talk about what the people think the oscillations are doing, particularly are faster ones. They're important in coordinating signals across neurons. Just like in a computer, a computer steps. So a computer knows when information is coming from another part of a computer that it

Starting point is 01:47:40 was originated at a particular time. And so that the screen step by step thing is important and computer control. Now the brain is not a digital device. It's an analog device. But when I have a signal that coming in my ear and my eye, which is Angel Eubim and speaking, and I'm looking at his face, I see that as a whole.

Starting point is 01:48:02 But the signal is coming into different parts of my brain. How do I unify that? Well, my neurons are very sensitive to changes in signals arriving by fractions of a millisecond. So how do I ensure that those signals coming in represent the same signal? Well, if I have to write my brain in an oscillation and the signals write on that oscillation, let's say the peak of the oscillation, I can then have a much better handle on the road of timing and say those two signals came in at the same time, they may relate to the same object and a heart, I see you as one unified thing

Starting point is 01:48:39 spouting, you know, talking. And so these oscillations come in many different frequency ranges and are important in memory formation and all sorts of things. I don't think people pay much attention to breathing because it's relatively slow to this, the range when you think about milliseconds. But we have important things that are thought to be important in cognitive function, which are a few cycles per second to 20, 30, 40, 50 cycles per second. Breathing in humans is maybe point two cycles per second, every five seconds, although in Rome, they're up to four per second, which is pretty fast. But breathing has one thing which is special,

Starting point is 01:49:29 that is you can readily change it. So the degree to which the brain is using that slow signal for anything, if that becomes part of its normal signal processing, you now change it, that signal processing, you now change it. That signal processing has to change. And as that signal processing changes, acutely there's a change. So you asked about breath practice. How long do you have to do it?

Starting point is 01:49:59 Well, a signal breath will change your state. You know, you're nervous. You take a deep breath and it seems to help relax or even die. Call it what you will. It seems to work. Now, it doesn't have a permanent change, but you know, when I'm getting up to bat or getting up to the first tea or getting to give a big block or coming to do a podcast, get a little bit anxious, a deep breath, a few deep breaths, a tremendously effective in calming one down. And so you can

Starting point is 01:50:39 get a transient disruption, but on the other hand, let's take something like depression. I think you can envision depression as activity sort of going around in a circuit. And because it's continuous in the nervous system as signals keep repeating, they tend to get stronger. And then you get so strong, you can't break them. So you can imagine depression being something going on and on and on, and you can't break it. And so we have trouble when we get to certain

Starting point is 01:51:18 levels of depression. I mean, all of us get depressed at some point, but if it's not continuous, it's not one last thing, we're able to break it. But if it's not continuous, it's not one last thing, we're able to break it. But if it's long lasting and very deep, we can't break it. So the question is, how do we break it? Well, there are extreme measures to break it. We could do electro-combulsive shock. We shock the whole brain. That's disrupting activity and the whole brain. And when this circuit starts to get back together again, it's been disruptive, and we know that the brain, when signals get disrupted a little bit, we can weaken the connections. And weakening the connections of its end in the circuit evolved

Starting point is 01:51:57 in depression, we may get some relief. An electro-chromosophage shock does work for relieving many kinds of depression. That's pretty heroic. Focal deep brain stimulation does the same thing but more localized or trans cranial stimulation. You disrupting a network. And while it's getting back together, it may weaken some of the connections. If breathing is playing some role in this circuit, and now,

Starting point is 01:52:28 instead of doing like a, you know, one second shock, I do 30 minutes of disruption by doing slow breathing or other breathing practice, the circuits begin to break down a little bit, and I get some relief. And if I continue to do it before the circuit can then build back up again, I gradually can weigh that circuit down. I sort of liken this, I tell people it's like walking around on a dirt path. You build a rot, to rot get so deep you can't get out of it. And what breathing is doing is sort of filling in the rut bit by bit to the point that you can climb out of that rut. And that is because breathing, the breathing signal is playing some role in the way the circuit works.

Starting point is 01:53:16 And then when you disrupt it, the circuit gets a little thrown off kilter. And as you know, when circuits get thrown off, the nervous system tries to adjust in some way or another and it turns out at least for breathing for some evolutionary reason or just by happenstance, it seems to improve our emotional function or our cognitive function. You know, we're very fortunate that that's the case. And, you know, we're very fortunate that that's the case. It's a terrific segue into what I want to ask you next. And this is part of a set of questions.

Starting point is 01:53:52 I want to make sure we touch on before we wrap up, which is, what do you do with all this knowledge in terms of a breathing practice? You mentioned that one breath can shift your brain state and that itself can be powerful. I think that's absolutely true. You've also talked about 30-minute breath-work practices, which is 30 minutes of breath work is a pretty serious commitment. I think, but it's doable. Certainly is zero cost except for the time, for in most cases, what do you see out there in the landscape of breathwork that's being done that you like? And why do you like it? What do you think, or what would you like to see more of in terms of exploration of breathwork? And what do you do?

Starting point is 01:54:42 What do you do? Well, I'm a well of the new convert to breathwork through my own investigation of it that became convinced that it's real. And I'm basically a beginner in terms of my own practice. And I like to keep things simple. And I think I've discussed this before. I liken it to someone who's a couch potato who's told they got to begin to exercise.

Starting point is 01:55:11 You don't go out and run a marathon. So couch potato, you say, OK, get up and walk for five minutes, 10 minutes, and then, OK, now you're walking for a longer period, you begin to run. And then you reach a point and say, well, gee, I'm interested in this sport. And there may be particular kinds of practices that you can use that could be helpful in optimizing performance of that sport. I'm not there yet. I find I get tremendous benefit by relatively short periods between five and maybe 20 minutes of doing box breathing.

Starting point is 01:55:49 It's very simple to do. I have a simple app which helps me keep the timing. Do you recall what you have? Is it the app near trainer? Is that the one? Well, I was using COM for a long time, but I let my subscription relax, and I have another one whose name I don't remember. But it's very simple, and it works for me. Now trying this tomo, because I'm just curious and exploring

Starting point is 01:56:17 it, because it may be acting through a different way. And I want to see if I respond differently. So I don't have a particular point of view. and I want to see if I respond differently. So I don't have a particular point of view now. I have friends and colleagues who are into, particular styles like Wim Hof, and I think what he's doing is great and getting people who are interested. I think the notion is that I would like to see

Starting point is 01:56:43 more people exploring this. And to some degree, as you point out, 30 minutes a day, some of the breath patterns that some of these stars like Wim Hof are a little intimidating to newbies. And so I would like to see something very simple that people would like to tell my friends. Just look, just try it five or ten minutes See if you feel better do for a few days if you don't like it stop it. It doesn't cost anything and Invariably they find that it's helpful. I will often interrupt my day

Starting point is 01:57:22 To take five or ten minutes like if I find that I'm lagging, you know, there's, I think there's some pretty good data that your performance you have to launch to clients. And so very often what I'll do, we have to launch, which I did today, is take five or ten minutes in just sort of breath practice. And lately, what does that breath practice look like? It's just box breathing for five or 10 minutes.

Starting point is 01:57:47 And the duration of your inhales and holds and exhales and holds is set by the app, is that right? Well, I do five seconds. So five seconds, inhale, five second hold, five second exhale, five second hold. And sometimes I'll do doubles. I'll do 10 seconds. Just because I get bored, you know,

Starting point is 01:58:07 it's just, I feel like doing it. And it's very helpful. I mean, now that's not the only thing I do with respect to trying to maintain my sanity and my health. No, I can imagine that there can be a number of things. Although you seem, because you seem very sane and very healthy, I in fact know that you are both those things. Well, you're suspect I don't use that.

Starting point is 01:58:31 I suspect. But there's data. A while back, we had a conversation, casual conversation, but you said something that really stuck in my mind, which is that it might be that the specific pattern of breath work that one does is not as important as experiencing transitions between states based on deliberate breath work, or something to that extent, which I interpreted to mean that if I were to do box breathing with five second in, five second whole, five second exhale, five second hold for a couple of days, or maybe even a couple of minutes,

Starting point is 01:59:08 and then switch to 10 seconds, or then switch to two more, that there's something powerful perhaps in the transitions and realizing the relationship between different patterns of breathing in those transitions. Much in the same way that you can get onto into one of these cars in a amusement park that

Starting point is 01:59:25 just goes at a constant rate and then stops. Very different than learning how to shift gears, you know, I used to drive a manual. I still can't start off thinking about a manual transmission, but even with an automatic transmission, you start to get a sense of how the vehicle behaves under different conditions. And I thought that was a beautiful seed for a potential breathwork practice that at least to my awareness, nobody has really formalized, which is that you introduce some variability within the practice that's somewhat random in order to be able to sense the relationship between different speeds and depths of inhales, exhales, and holds, and so forth.

Starting point is 01:59:58 And essentially it's like driving around the track, but with obstacles at different rates and breaking and restarting and things like that. That's how you learn how to drive. What do you think about that? If you like it enough, can we call it the Feldman Protocol? Oh, please. I was asked in this BBC interview once, why didn't I name it the Feldman Complex? It's at the pre-butt's who accomplished it.

Starting point is 02:00:23 You said I already have a Feldman Complex. so the pre-butts are accomplished. You said, I already have a Feldman Complex. Well, it sounds like a psychiatric disorder, but I think the primary effect is this disruptive effect, which I described, and but the particular responses may clearly vary depending on what that disruption is. I don't know of any particular data which are some well-controlled experiments which can actually work through the different types of breathing patterns or simply with a box

Starting point is 02:00:58 pattern, just varying the durations. I mean, cryomas sort of similar, but the amount of time you spend going around the box is different. So I don't really have much to say about this. I mean, this is why we need better controlled experiments in humans. And I think this is where being able to study and in rodents, where you can have a wide range of perturbations while you're doing more invasive studies to really get down as to which regions are affected.

Starting point is 02:01:33 How is the signal processing disrupted, which is still hypothesis, but how is disrupted? Could tell us a lot about, you know, maybe there's a resonant point at which there's an optimal effect when you take a particular breathing practice. And then when we talked about the fact that different breathing practices could be affecting the outcomes through different pathways. You have the olfactory pathway, you have a central pathway, you have a vagal pathway, you have a descending

Starting point is 02:02:05 pathway, how different practices may change the summation of those things, because I think all those things are probably involved. And we're just beginning to scratch the surface. surface. And I just hope that we can get serious, you're a scientist and psychologist to do the right experiments to get at this, because I think there's a lot of value to human health here. I do too. And it's one of the reasons my lab has shifted to these sorts of things. In humans, I'm delighted that you're continuing to do the hardcore mechanistic work in mice and probably do work in humans as well, if you're not already. And there are other groups, Apple, Lab at UCSF and a number of, I'm starting to see some papers out there about respiration in humans a little bit, some more brain imaging. I can't help but ask about a somewhat unrelated

Starting point is 02:03:04 topic, but it is important in light of this conversation because you're here. And one of the things that I really enjoy about conversations with you as it relates to health and neuroscience and so forth is that you're one of the few colleagues I have who openly admits to exploring supplementation. I'm a long time supplement fan. I think there's power in compounds, both prescription, non-prescription, natural, synthesized. I don't use these have hazardly, but I think there's certainly power in them.

Starting point is 02:03:45 And one of the places where you and I converge in terms of our interest in the nervous system and supplementation is these are the magnesium. Now I've talked at endlessly on the podcast and elsewhere about magnesium for sake of sleep and improving transitions to sleep and so forth. But you have a somewhat different interest in magnesium as it relates to cognitive function and durability of cognitive function. Would you mind just sharing with us a little bit about what that interest is where it stems from? And because it's the human lab podcast and we often talk about supplementation, what you

Starting point is 02:04:24 do with that information. So I need to disclose that I am a scientific advisor to a company called North Century, which my graduate student, Quosong Lu is CEO. So that said, I can give you some background. Quosong, although he was in my lab work done breathing, had a deep interest in learning and memory. And we left my lab, he went to work for it

Starting point is 02:04:49 with a renowned learning and memory guy, at Stanford Diction. And when he finished there, he was hired by Susumu Tonigawa and MIT. Who also knows a thing or two about memory. I'm teasing. Susumu has a Nobel for his work on Immunoglobulins, but then is a world-class memory researcher.

Starting point is 02:05:10 Yeah. And more. He's many things. And Gwasung had very curious, very bright guy. And he was interested in how signals between neurons get strengthened, which is called long-term potentials in LTP. And one of the questions that arose was if I have inputs to a neuron, and I get LTP, is the LTP bigger if the signal is bigger or the noise is less.

Starting point is 02:05:47 So we can imagine that when we're listening to something of its louder, we can hear it better, or if there's less noise, we can hear it better. And he wanted to investigate this. So I did this in tissue culture of hippocampal neurons. And what he found was that if he lowered the background activity in all of the neurons, that the LTP he elicited got stronger. And the way he did that was increasing the level of magnesium in the bathing solution.

Starting point is 02:06:22 This gets into some esoteric electrophysiology, but basically there's a background level of noise and onerones, and that part of it is regulated by the degree of magnesium in the exocereal of bath. And you mean electrical noise. Electrical noise, some sort of electrical noise. And if you, in what's called the physiological range, which is between 0.8 and 1.2 millimolar,

Starting point is 02:06:54 which don't worry about the number. You can't remember the millimolar of the magnesium. Well, I'm always frightened that I get, you know, I say micro or phantom or something, I go off by several orders of magnitude. So, in that physiological range, there's a big difference in the amount of noise in a neuron between 0.8 and 1.2 millimode. So, key played around with the magnesium. Many found out that when the magnesium was elevated, it was more LTP.

Starting point is 02:07:24 All right, that's an observation in a tissue culture. And I should just mention that more LTP essentially translates to more neuroplasticity, more rewiring of connections in essence. So he tested this in mice, and basically he offered them a, he had control mice, which got a normal diet and one that had, one that reached the magnesium. And the ones that lived in rich with magnesium had higher cognitive function, lived longer, everything you'd want in some magic pill, those mice did that,

Starting point is 02:08:02 Those mice did that. I actually rats. The problem was that you couldn't imagine taking this into humans because most magnesium salts don't passively get from the gut into the bloodstream into the brain. They pass via what's called a transporter. Transporter is something in a membrane that grabs a magnesium molecule or atom and pulls it into the other side. So if you imagine you have magnesium in your gut, you have transporters that pull the magnesium

Starting point is 02:08:39 into the gut into the bloodstream. Well, if you had to take taken normal magnesium supplement that you can buy at the pharmacy, it doesn't cross the gut very easily. And if you would take enough of it to get it in your bloodstream, you start getting diarrhea. So it's not a good way to go. What is a good way to go? Oh, sorry. Couldn't help myself. Well, I'll say. So he worked with this brilliant chemist, Fey Mow, and Fey looked at a whole range of magnesium compounds,

Starting point is 02:09:20 and he found the magnesium 3 and 8 was much more effective in crossing the gut blood barrier. Now, they didn't realize at the time, but 3-8 is a metabolite of vitamin C. And there's lots of 3-8 in your body. So, magnesium 3-8 would appear to be safe. And maybe part of the role, or now they believe it's part, the role of the free innate is that it supercharges the transporter to get the magnesium in. And remember, you need a transporter to the gut, into the brain, and into cells. So they gave magnesium niece in 3-8 to mice, who had, no, let me backtrack a bit. They did a study in humans. They hired a company to do a test.

Starting point is 02:10:15 It was a hands-off test. It's one of these companies that gets hired by the big farmer to do their tests for them. And they got patients who had were diagnosed as malcognitive decline. These are people who had cognitive disorder, which was age inappropriate. And the method that they use for determining how far off they were is Spirman's G factor, which

Starting point is 02:10:43 is a generalized measure of intelligence that most psychologists accept. And the biological age of the subjects was, I think, 51, and the cognitive age was 61 based on the Spirman G Test. I should say the Spirman G factor starts at a particular level in the population at age 20 and declines about 1% a year. So sorry to say we're not 20-year-olds anymore. But when you get a number from that, you can put on the curve and see whether it's about your Asian knot. These people are about 10 years older according to that metric.

Starting point is 02:11:32 And long story short, if the three months, this is a placebo-controlled double-blind study, the people who are in the placebo arm improved two years, which is common for human studies, cause of placebo effect. The people who got the compound improved eight years on average. And some improved more than eight years. They didn't do any further diagnosis of what caused the metabolic problem to climb, but it was pretty, it was extraordinarily impressive. So it moved their cognition closer

Starting point is 02:12:09 to their biological age. Biological age. Do you recall what the doses of magnesium three and a half? It's in the paper and it's basically what they have in the compound which is sold commercially. So the compound which is sold commercially. So the compound which is sold commercially is handled by a nuchasutical wholesaler who sells it to the retailers and they make whatever formulation they want.

Starting point is 02:12:36 But it's a dosage which is minus than is rarely tolerable. I take half a dose. The, I take half a dose. The reason I take half a dose is that I had my museum, blood my museum measure, and it was low normal for my age. I took half a dose and became high normal. And I felt comfortable staying in the normal range. But, you know, a lot of people are taking the full dose. And, um, at my age, I'm not looking to get smarter.

Starting point is 02:13:15 I'm looking to decline more slowly. And it's hard, you know, it's hard for me to tell you whether or not it's effective or not. Well, you remembered the millimolar of the magnesium and the solution and the high and low end. So I would say it's not a well-controlled study when it's an end of the month, but it seems to be working. When I've recommended to my friends, academics who are not by nature skeptical, if not cynical,

Starting point is 02:13:43 and insist that they try it. They usually don't report a major change in their cognitive function, although sometimes they do report while I feel a little bit more alert and my physical movements are better, but many of them report they sleep better. And that makes sense.

Starting point is 02:14:02 I think there's good evidence that three and eight can accelerate the transition into sleep and maybe even access to deeper modes of sleep for some people. There are, for many people, actually, a small percentage of people who take 3 and 8, including one of our podcast staff here, have stomach issues with it. They can't tolerate. I would say, just anecdotally, about 5 it. They can't tolerate. I would say just anecdotally, about 5% of people don't tolerate 3 and 8.

Starting point is 02:14:28 Well, stop taking it and then they're fine. It caused them diarrhea or something in that sort. But most people tolerate it well. And most people report that it vastly improves their sleep. And again, that's anecdotally. There are a few studies and they're more on the way. But that's very interesting because I, until you and I had the discussion about three and eight, I wasn't aware of the

Starting point is 02:14:50 cognitive enhancing effects. But the story makes sense from a mechanistic perspective. And it brings it around to a bigger and more important statement, which is that I so appreciate your attention to mechanism. I guess this stems from your early training as a physicist and the desire to get numbers and to really parse things at a fine level.

Starting point is 02:15:12 So, we've covered a lot today. I know there's much more that we could cover. I'm going to insist on a part two at some point, but I really want to speak on behalf of a huge number of people and just thank you, not just for your time and energy and attention to detail and accuracy and clarity around this topic today. But also what I should have said at the beginning, which is that you really are a pioneer in this field of studying respiration and the mechanisms underlying respiration with modern tools for now for many decades. And the field of neuroscience was one that was perfectly content to address issues like memory and vision and sensation perception et cetera, but the respiratory system was largely overlooked

Starting point is 02:15:59 for a long time and you've just been steadily clipping away and clipping away and much because of the events of related to COVID and a number of other things and this huge interest in breathwork and brain states and wellness, the field of respiration and interest in respiration is just exploded. So I really want to extend a sincere thanks. It means a lot to me and I know to the audience of this podcast that someone with your depth and rigor in this area is both a scientist and a practitioner and that you would share this with us. So, thank you.

Starting point is 02:16:35 Well, I want to thank you. This is actually a great opportunity for me. I've been isolated in my silo for a long. And it's been a wonderful experience to communicate to people outside the silo, have an interest in this. And I think that there's a lot that remains to be done. And I enjoy speaking to people who have interest in this. I find the interest to be quite mind-boggling. And it's quite wonderful that people are willing to listen to things that can be quite esoteric

Starting point is 02:17:08 at times, but it gets down to deep things about who we are and how we are going to live our lives. So I appreciate the opportunity and I would be delighted to come back at any time. Wonderful. We will absolutely do it. Thanks again, Jack. Bye now. Thank you for joining me for my conversation with Dr. Jack Feldman.

Starting point is 02:17:28 I hope you found it as entertaining and as informative as I did. If you're learning from and or enjoying this podcast, please subscribe to us on YouTube. That's a terrific zero-cost way to support us. In addition, please subscribe to the podcast on Spotify and Apple. And on Apple, you can leave us a review and you can leave us up to a five-star rating. Please also check out the sponsors mentioned at the beginning of the podcast. That's the best way to support this podcast. In addition, if you're not already following us on Instagram and Twitter,

Starting point is 02:17:57 I teach neuroscience on Instagram and Twitter. Some of that information covers information covered on the podcast. Some of that information is unique information. And that includes science and science based tools that you can apply in everyday life. And as mentioned at the beginning of today's episode, we are now partnered with Momentus supplements because they make single ingredient formulations that are of the absolute highest quality and they ship international. If you go to livemomentus.com slash huberman, you will find many of the supplements that

Starting point is 02:18:24 have been discussed on various episodes of the Huberman Lab podcast, and you will find various protocols related to those supplements. I also want to just mention one more time. The program that I mentioned at the beginning of the episode, which is our breath collective, the our breath collective, has an advisory board that includes people like Dr. Jack Feldman, where you can learn detailed breath work protocols. If you're interested in doing or teaching breath work, I highly recommend checking it out. You can find it at ourbreathcollective.com slash Huberman, and that will give you $10 off

Starting point is 02:18:53 your first month. So I want to thank you once again for joining me for my conversation with Dr. Jack Feldman and last but certainly not least, thank you for your interest in science. Thank you for your interest in science.

Huberman Lab - Dr. Jack Feldman: Breathing for Mental & Physical Health & Performance

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