Breathing for Mental & Physical Health & Performance | Dr. Jack Feldman

1. 0:00 – 3:05

   Introducing Dr. Jack Feldman

   1. AHAndrew Huberman0:00

      (Music) 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 colleagues tells us, breathing is also fundamental to organ health and function at an 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 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 the brain to be in particular states that can benefit us all. Whether or not you are a person who already practices breath work, 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 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, is not only at the top of his field, he founded the field. 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, and I know that you're not only going to enjoy it, but you are going to learn a tremendous amount.

2. 3:05 – 10:35

   Sponsors: Thesis, Athletic Greens, Headspace, Our Breath Collective

   1. AHAndrew Huberman3:05

      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 Thesis. Thesis is a company that makes nootropics. Now, I've talked before on the podcast and elsewhere about the fact that I don't really like the term nootropics, which means smart drugs, because smart means many different things in many different contexts. You've got creativity, you've got focus, you've got task-switching. So the idea that there would be one pill or one formula that could m- make us smarter and better at all those things at once just doesn't stand up to logic. In fact, different chemicals and different brain systems underlie our ability to be creative or our ability to task-switch or to be focused. And that's the basis of Thesis. Thesis is a company that makes targeted nootropics for specific outcomes. In other words, specific nootropics to get your brain into states that are ideal for what you're trying to accomplish. Thesis uses very high-quality ingredients, many of which I've talked about before on the podcast, such as DHA, ginkgo biloba, and phosphatidylserine. I talked about those in the ADHD podcast. Those are some of the ingredients in their so-called Logic formula. There's a lot of research showing that ginkgo biloba can be very helpful for increasing levels of focus, and even for people with ADHD. However, I can't take it. When I take it, I get really bad headaches, and I know some people who do and some people who don't get headaches when they take ginkgo biloba. This is a great example of why nootropics need to be personalized to the individual. Thesis gives you the ability to try different blends over the course of a month and discover which nootropic formulas work best for your unique brain chemistry and genetics, and which ones are best for particular circumstances. So they have a formulation, for instance, which is Motivation. They have another formulation which is Clarity. They've got another formulation which is Logic. And each of these is formulated specifically to you and formulated to a specific end point or goal state of mind for your particular work. So as a consequence, the formulations that you arrive at will have a very high probability of giving you the results that you want. In addition to that detailed level of personalization, Thesis takes it a step further by offering free consultations with a brain coach to help you optimize your experience and dial in your favorite and best formulas. I've been using Thesis for close to six months now and I can confidently say that their nootropics have been a total game changer for me. My favorite of the formulations is their Motivation formula that they've tailored to me. When I use that formula, I have very clear state of mind, I have even energy, and I use that early in the day until the early afternoon to get the bulk of my most important work done. To get your own personalized nootropic starter kit, you can go online to takethesis.com/huberman, take a three-minute quiz, and Thesis will send you four different formulas to try in your first month. That's takethesis.com/huberman and use the code Huberman at checkout to get 10% off your first order.Today's episode is also brought to us by Athletic Greens. Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been using Athletic Greens since 2012, and 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 is that it covers all of my vitamin, mineral, and probiotic foundational needs. There's now a wealth of data showing that not only do we need vitamins and minerals, but we also need to have a healthy gut microbiome. The gut microbiome is a set of nerve connections that link the microbiota, literally microbacteria that live in our guts and that are healthy for us, with our brain function, and our brain is also talking to our gut in a bidirectional way, and that conversation is vital for metabolism, for the endocrine system, meaning the hormonal system, and for overall mood and cognition. There's just so much data now pointing to the fact that we need a healthy gut microbiome and a healthy brain-gut axis, as it's called. By taking Athletic Greens once or twice a day, I can get the vitamins, the minerals, and the probiotics needed for all those systems to function optimally, and again, it tastes great. It's great for me. In fact, if people ask me, "What's the one supplement that I should take?" and they can only take one supplement, I recommend Athletic Greens for all the reasons I mentioned. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman to claim a special offer. They're giving you five free travel packs, which are these little travel packs that make it easy to mix up Athletic Greens while you're on the road or in the car or on the plane, et cetera, and a year's supply of vitamin D3 K2. There is also a wealth of evidence showing that vitamin D3 is vital to our overall health and K2 is important for cardiovascular health and other systems as well. Most of us are not getting enough vitamin D3 or K2 even if we're getting some sunshine. So again, if you go to athleticgreens.com/huberman, you get the five free travel packs, a year's supply of vitamin D3 K2. Athleticgreens.com/huberman is where you go to claim that special offer. Today's episode is also brought to us by Headspace. Headspace is a meditation app that's supported by 25 published studies and benefits from over 600,000 five-star reviews. I've long been a believer in meditating. There is so much data now pointing to the fact that regular meditation leads to reduced stress levels, heightened levels of focus, better task switching and cognitive ability. It just goes on and on. I mean, there are literally thousands of peer-reviewed studies now and quality journals pointing to the benefits of having a regular meditation practice. The problem with meditation is many people, including myself, have struggled with sticking to that practice. With Headspace, it makes it very easy to start and continue a meditation protocol. The reason for that is they have meditations that are of different lengths and different styles so you don't get bored of meditation, and even if you just have five minutes, there are five-minute meditations. If you've got 20 minutes, which would be even better, there are 20-minute meditations. Ever since I started using Headspace, I've been consistent about my meditation. I do meditation anywhere from five to seven times a week in my best weeks, and sometimes that drops to three, and then I find with Headspace I can quickly get back to doing meditation every day because of the huge variety of great meditations that they have. If you want to try Headspace, you can go to headspace.com/specialoffer, and if you do that, you can get a free one-month trial with Headspace's full library of meditations for every situation. That's the best deal offered by Headspace right now. So again, if you're interested, go to headspace.com/specialoffer. 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 those will be accessible to you. However, I am aware that there are a number of people out there that want to 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 OurBreathWorkCollective. I'm not associated with the Breathwork Collective, but Dr. Feldman is an advisor to the group, and they offer daily live guided breathing sessions and an on-demand library that you can practice any time, free workshops on breathwork, 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 and their work and it is of the utmost quality. So anyone wanting to learn or teach breathwork could really benefit from this course, I believe. If you'd like to learn more, you can click on the link in the show notes or visit ourbreathworkcollective.com/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 ourbreathworkcollective.com/huberman to access the Our Breath Collective. And now for my conversation with Dr. Jack Feldman.

3. 10:35 – 14:35

   Why We Breathe

   1. AHAndrew Huberman10:35

      Thanks for joining me today.

   2. JFDr. Jack Feldman10:37

      It's a pleasure to be here, Andrew.

   3. AHAndrew Huberman10:38

      Yeah, it's been a long time coming. You're my go-to source for all things respiration.

   4. JFDr. Jack Feldman10:43

      (laughs)

   5. AHAndrew Huberman10:43

      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.

   6. JFDr. Jack Feldman10:52

      Well, I'll do my best. As you know, there's a lot that we don't understand, which still keeps me employed and engaged, but, uh, we do know a lot.

   7. AHAndrew Huberman11:00

      Why don't we start off by just talking about what's involved in generating breath, and if you would, um, could you comment on some of the mechanisms for rhythmic breathing versus non-rhyth- rhythmic breathing?

   8. JFDr. Jack Feldman11:17

      Okay. So on the mechanical side, which is obvious to everyone, we, um, want to have air f- flow in, inhale, and we need to have air flow out. And the reason we need to do this is because for body metabolism we need oxygen, and when oxygen's utilized through the meta- aerobic metabolic process, we produce carbon dioxide, and so we have to get rid of the carbon dioxide that we produce, in particular because the carbon dioxide affects the acid-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 air flow? Well, the air comes into the lungs. We have to expand the lungs, and as 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 the, put pressure on the lung to pull it apart, that lowers the pressure in the air sacs, called alveoli, 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. What produces that? Well, the principle muscle is a d- the 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 exerting pressure forces on the lung. The lung wants to expand. At the same time, the ribcage is going to rotate up and out, and therefore expanding the- the cavity, the thoracic cavity. 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 it relaxes. So you inhale (inhales) and you exhale (exhales) . Inhale, relax, and exhale.

   9. AHAndrew Huberman13:27

      So the exhale is passive?

   10. JFDr. Jack Feldman13:29

       Uh, at rest it's passive. We'll get into, uh, what happens when you need to increase, uh, the amount of air you're bringing in because your ventilation go- or your metabolism goes up, like during exercise. Um, now the muscles themselves, skeletal 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. So there are specialized neurons in the spinal cord and then 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 ribcage, and they contract. So these respiratory muscles, these inspiratory 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. Where

4. 14:35 – 16:20

   Neural Control of Breathing: “Pre-Botzinger Complex”

   1. JFDr. Jack Feldman14:35

      does that activity in the- these neurons that innovate the muscle, which are called motor neurons, where does that originate? Well, this was a question that's been bandied around for thousands of years, and when I was a, um, beginning assistant 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. And- and- I didn't phrase that properly. You couldn't understand how it was being done until you know where to look. So we did a lot of experiments, which I can go into detail, and finally found there was a region in the brainstem, that's once again this region sort of above the spinal cord, which was critical for generating this rhythm. It's called the preBotzinger 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 works in tandem, and 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 preBotzinger complex finish their burst of activity, then inspiration stops and then you begin to exhale because of this passive, um, recoil of the lung and ribcage.

5. 16:20 – 18:18

   Nose vs Mouth Breathing

   1. JFDr. Jack Feldman16:20

   2. AHAndrew Huberman16:20

      Could I, uh, just briefly interrupt you to ask a few quick questions-

   3. JFDr. Jack Feldman16:23

      Of course.

   4. AHAndrew Huberman16:23

      ... before, um, we move, uh, forward in this, uh, very informative, uh, answer? And the- the two questions are, um, is there anything known about the activation of the diaphragm and the intercostal muscles between the ribs as it relates to nose versus m- mouth breathing, or are they activated, uh, in the equivalent way regardless of whether or not someone is breathing through their nose or mouth?

   5. JFDr. Jack Feldman16:52

      Uh, I- I don't think we fully have the answer to that. Clearly there are differences between nasal and mouth breathing. Um, at rest, the tendency is to do nasal breathing because the airflows, uh, that are necessary for normal breathing are s- easily, um, 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 then and therefore you can move much more air. But at the level of the intercostals and the diaphragm, their contraction, uh, is not, uh, is almost, uh, agnostic to whether or not the nose and mouth are open.

   6. AHAndrew Huberman17:39

      Okay, so there, if I understand correctly, um, there's no reason to suspect that there are particular, perhaps even non-overlapping sets of neurons in preBotzinger area of the brainstem that trigger nasal versus mouth inhales?

   7. JFDr. Jack Feldman17:55

      No. I would say that the- there's th- it's not that the preBotzinger complex is not concerned and cannot influence that, but it does not appear as if there's any, uh, uh, 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.

   8. AHAndrew Huberman18:14

      All right. Thank you, and then the other question I have is the- these intercostal

6. 18:18 – 20:11

   Skeletal vs. Smooth Muscles: Diaphragm, Intracostals & Airway Muscles

   1. AHAndrew Huberman18:18

      muscles between the ribs that move the- the ribs up and out, if I understand correctly, and the diaphragm, uh-... are those skeletal, or as the Brits would say, skeletal (muscles) , muscles, or smooth muscles? What type of muscle are, are we talking about here?

   2. JFDr. Jack Feldman18:32

      A- as, as I said earlier, these are skeletal... I didn't say they were skeletal muscles, but they're muscles that need neural input in order to move. You talked about smooth muscles. Uh, they are specialized muscles like we have in the gut and in the heart, and these are muscles that are capable of actually m- contracting and relaxing on their own. So, the heart beats. It doesn't need neural input in order to beat. It... The neural inputs modulate the strength of it and the frequency, but they beat on their own. The skeletal muscles involved in breathing are... need neural input. Now, there are smooth muscles that have an influence on breathing, and these are muscles that align in 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 in asthma. Asthma is a condition where you get inappropriate constriction of the smooth muscles of the airways.

   3. AHAndrew Huberman19:40

      So, there's no reason to think that in asthma that the preBotzinger or these other neuronal centers in the brain that could... that activate breathing, that they are involved or causal for, for things like asthma?

   4. JFDr. Jack Feldman19:52

      As of now, I would say the preponderance of evidence is that it's not involved, but we've not really fully investigated that.

   5. AHAndrew Huberman19:59

      Okay. Thank you. Sorry to break your flow-

   6. JFDr. Jack Feldman20:01

      No.

   7. AHAndrew Huberman20:01

      ... um, but I was terribly interested in, uh, knowing answers to those questions and you provided them, so thank you.

   8. JFDr. Jack Feldman20:08

      Um, now, remind me again where I was

7. 20:11 – 26:20

   Two Breathing Oscillators: Pre-Botzinger Complex & Parafacial Nucleus

   1. JFDr. Jack Feldman20:11

      in my...

   2. AHAndrew Huberman20:11

      We were just landing in preBotzinger and, um, we will return to the naming of preBotzinger 'cause it's a wonderful and important story really, uh, that I think people should, uh, be aware of. But yeah, maybe you could, um, march us through the brain centers that you've discovered, uh, and others have worked on as well, that control breathing. PreBotzinger as well as, um, related-

   3. JFDr. Jack Feldman20:34

      Okay.

   4. AHAndrew Huberman20:35

      ... structures.

   5. JFDr. Jack Feldman20:35

      So, we... When we discovered the preBotzinger, we thought that it was the primary source of all rhythmic respiratory movements, both inspiration and expiration. Uh, the notion of a single source is like day or night. It's like they're all coming... They all have the same origin that the earth rotates and day follows night, and we thought that the preBotzinger complex would be inhalation, exhalation. Um, and then in a series of experiments we, uh, did in the early part of 2000, we discovered that there seemed to be another region which was dominant in producing expiratory movements. That is, the exhalation. We had made a fundamental mistake through... sin- with the discovery of the preBotzinger, not taking into account that at rest, expiratory muscle activity or exhalation is passive. So, if that's the case, a group of neurons that might generate active expiration, that is to contract the expiratory muscles like the abdominal muscles or the internal intercostals, are just silent. We just thought it wasn't there. It 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, we discovered that there was a second oscillator, and that oscillator is involved in generating what we call active expiration. That is, this (inhales) active-

   6. AHAndrew Huberman22:16

      Like if I go shh.

   7. JFDr. Jack Feldman22:17

      Yeah.

   8. AHAndrew Huberman22:18

      Hoo.

   9. JFDr. Jack Feldman22:18

      Or when you-

   10. AHAndrew Huberman22:19

       Yeah.

   11. JFDr. Jack Feldman22:19

       ... begin to, uh, exercise and you have to go (inhales and exhales quickly) and actually move that air out. This group of cells, which is silent at rest, suddenly becomes active to drive those muscles, and it appears that it's an independent oscillator.

   12. AHAndrew Huberman22:35

       When, um... Maybe you could just clarify for people what an oscillator is.

   13. JFDr. Jack Feldman22:39

       Okay. Now, 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.

   14. AHAndrew Huberman22:50

       Some people's moods are oscillating.

   15. JFDr. Jack Feldman22:52

       Oscillating. And it depends how regular they are. You can have oscillators that are highly regular that are in a watch, uh, or you can have those that are sporadic or episodic. Breathing is one (laughs) of those oscillators that, for life, has to be working continuously, 24/7. It starts in the... late in the 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.

   16. AHAndrew Huberman23:25

       What is this second oscillator called?

   17. JFDr. Jack Feldman23:28

       Well, we found it, um, in a region around the facial nucleus. So, we initially... Uh, when this region was initially identified, it... we thought it was involved in sensing carbon dioxide. It was what we call a central chemoreceptor. That is, we want to keep carbon dioxide levels, particularly in the brain, at a relatively stable level, 'cause the brain is extraordinarily sensitive to changes in pH. If there's a big shift in s- carbon dioxide, they'll be a sh- big shift in brain pH, and that'll throw your brain, if I can use the technical term, out of whack.

   18. AHAndrew Huberman24:08

       Mm-hmm.

   19. JFDr. Jack Feldman24:08

       And so, you want to regulate that, and the way to regulate something in the brain is you have a sensor in the brain, and, uh, others basically identified that the ventral surface of the brainstem, that is, the part of the brainstem that's on this side, um...... was critical for that, and then we identified a structure that we, um, was near the trapezoid nucleus. It was not named in any of these neuroanatomical atlases, so we just picked a name out of a hat and we called it the retrotrapezoid nucleus.

   20. AHAndrew Huberman24:44

       I should clarify for people, when we, uh, when, um, Jack is saying trapezoid, he doesn't mean the trapezoid muscles. Trapezoid refers to the shape, uh, of this nucleus, this cluster of neurons. Um, parafacial makes me think that this general area is involved in something related to mouth or face. Um, is it an area rich with, uh, neurons controlling other parts of the face? Eye blinks, nose twitches, um, lip curls, lip smacks?

   21. JFDr. Jack Feldman25:13

       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, uh, c- control of facial muscles, going back to more primitive creatures because they had to take things in their mouth for eating, so they, we call that the f- and the face sort of developed. The eyes were there. The mouth was there. These (laughs) nuclei, the motor n- 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 subnuclei around there that had various roles 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 mo- moving air in and out of the mouth. And so part of that s- of these many different subnuclei now seems to be in mammals to be involved in the control of expiratory muscles. But we have to

8. 26:20 – 33:40

   How We Breathe Is Special (Compared to Non-Mammals)

   1. JFDr. Jack Feldman26:20

      r- 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, and there are lots of theories about how it developed. I don't think it's particularly clear. There was a, uh, uh, something you can find in alligators and lizards that could've turned into a muscle that was a di- the diaphragm. The amazing thing about the diaphragm is that it's mechanically extremely efficient, and what do I mean by that? Well, if you, 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 alveolus 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 alveolus into the blood.

   2. AHAndrew Huberman27:50

      Which is amazing. I find that amazing. Even though-

   3. JFDr. Jack Feldman27:53

      Okay.

   4. AHAndrew Huberman27:53

      ... it's just purely mechanical, the idea that we have these little sacs in our lungs. We inhale and the air goes in, and literally the oxygen get, can pass into the bloodstream.

   5. JFDr. Jack Feldman28:01

      Passes into the bloodstream, but the, the rate at which it passes will depend on the characteristics of the membrane, how, what the distance is between the alveolus and the, the blood vessel, the capillary, but it, 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 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 bit o', a little sphere, which is an alveolus. And that determines what the surface area is going to breed- be. Now, you then have a mechanical problem. You have this surface area. You have to be able to pull it apart. So imagine you have a little square of e- elastic membrane. It doesn't take a lot of force to pull it apart, but now if you in- 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, 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, relative 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 500 million alveoli.

   6. AHAndrew Huberman29:48

      How, h- if we were to take those four to five million ave- uh, alveoli-

   7. JFDr. Jack Feldman29:51

      Four, hundred million.

   8. AHAndrew Huberman29:52

      Hundred-

   9. JFDr. Jack Feldman29:52

      Four to five-

   10. AHAndrew Huberman29:54

       Four to f-

   11. JFDr. Jack Feldman29:54

       ... hundred million.

   12. AHAndrew Huberman29:54

       Hundred million, excuse me, um, and lay those out flat, what sort of surface area are we talking about?

   13. JFDr. Jack Feldman30:00

       About s- 70 square meters, which is about a third the size of a tennis court.

   14. AHAndrew Huberman30:04

       Wow.

   15. JFDr. Jack Feldman30:05

       So you have a membrane inside of you a third the size of a tennis court that you actually have to expand every breath, and you do that without exerting much of a, uh, 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.

   16. AHAndrew Huberman30:31

       Wow.

   17. JFDr. Jack Feldman30:31

       Now, the, the, at rest...... the volume of air in your lungs is about two and a half liters. Do we need to convert that to quarts?

   18. AHAndrew Huberman30:42

       No.

   19. JFDr. Jack Feldman30:43

       All right, so about two and a half liters. When you take a breath, you take in another 500 milliliters or half a liter. That's the size, maybe, a lit- of my fist. So, you're increasing the volume by 20%, but you're, 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, 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, we have this amazing, um, mechanical advantage by having a diaphragm. Uh-

   20. AHAndrew Huberman31:37

       Do you think that, 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?

   21. JFDr. Jack Feldman31:46

       I would say a key step in the ability to develop a large brain that has a continuous demand for oxygen is the diaphragm. Without a diaphragm, you're an amphibian. And there... and, and there- there's another solution to increasing oxygen uptake which is the way birds breathe, but birds have other limitations, and they still can't get brains as big as, uh, mammals have. So we, we, the, uh... The brain utilizes maybe 20% of all the oxygen that we intake, and it needs it continuously. You can't... 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 ph- very pliant ribcage, and now you have to develop into an adult, which has a stiffer ribcage. And so there are changes happening in your brain and your body where breathing, the neural control of breathing has to change on the fly. It's not like for things like vision, um, where you have the opportunity to sleep, and while you're sleeping, the brain is capable of doing things that are not easy to do during wakefulness, like the construction crew comes in during sleep. Uh, breathing has been, the change in breathing have been described as trying to build an airplane while it's, while it's flying.

   22. AHAndrew Huberman33:20

       Basically what Jack is saying is that, uh, respiration science is more complex and hard-working than vision science, which is a direct jab at me, um, that some of you might have missed, but I definitely did not miss, and I appreciate that you always, uh, take the opportunity like a good New Yorker to, to, you know, give me a good healthy, uh, intellectual jab.

9. 33:40 – 36:23

   Stomach & Chest Movements During Breathing

   1. AHAndrew Huberman33:40

      A question, um, related to diaphragmatic breathing versus non-diaphragmatic breathing, because the way you describe it, the diaphragm is always involved, but, you know, over the years, um, whether it be for, you know, a yoga class or a breath work thing or you hear online that we should be breathing with our diaphragm. That rather than lifting our ribcage when we breathe (inhales deep) and our chest, that it is "healthier" or better somehow to have the belly expand when we inhale. Uh, I'm not aware of any particular studies that really examined the direct health benefits of diaphragmatic versus non-diaphragmatic breathing, but if you don't mind commenting on anything you're aware of, uh, as it relates to diaphragmatic versus non-diaphragmatic breathing, whether or not people tend to be diaphragmatic breathers by default, et cetera. That would be, um, I think interesting to a number of people.

   2. JFDr. Jack Feldman34:34

      Well, I think by default, we are obligate diaphragm breathers. I, um... There may be pathologies where the diaphragm is compromised and you have to use other muscles, and that's a challenge. Um, it, uh... Certainly at rest, other muscles can take over, but if you need to increase your ventilation, the diaphragm is very important. It's, would be hard to increase your ventilation otherwise.

   3. AHAndrew Huberman35:05

      Do you pay attention to whether or not you are breathing in a manner where your belly, uh, goes out a little bit as you inhale? Because I can do it both ways, right? I can inhale (inhales deep) , bring my belly in, or I can inhale (inhales deep) , push my di- diaphragm and belly out. Um, not the diaphragm out, but... Uh, and that's interesting, right? Because it's a completely different muscle set for each, uh, each version.

   4. JFDr. Jack Feldman35:28

      Well, I... In the, in the context of things like breath practice, I'm a, a bit a- agnostic about the effects of some of the different patterns of breathing. Clearly some are going to 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. Uh, I think that the changes that, 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 you're choosing. But that just could be my own prejudice.

   5. AHAndrew Huberman36:17

      Okay. And we'll, we will return to that, um, as a general theme in a little bit. I,

10. 36:23 – 49:39

    Physiological Sighs, Alveoli Re-Filling, Bombesin

    1. AHAndrew Huberman36:23

       I want to ask you about sighing. Uh, one of the gr- many great gifts that you've given us over the years, uh, is an understanding of these things that we call physiological sighs. Um, could you tell us about physiological sighs, uh, what's known about them?... what your particular interest in them is, and, um, what they're good for.

    2. JFDr. Jack Feldman36:48

       Uh, a very interesting and important question. So, everyone has a, um, sense of what a sigh is. We certainly, when we're emotional, emotional in some ways, we're stressed, we're particularly happy, (gasps) we'll take a... we'll sigh. It turns out that we're sighing all the time, and, uh, when I would ask people who are not particularly knowledgeable, that haven't read my papers or James Nestor's book or listened to your podcast, um, they're usually off by two orders of magnitude about how frequently we sigh on the low side. In other words, they say, oh, once an hour, you know, 10 times a day. We sigh about every five minutes, and I would, uh, encourage anyone who finds that to be, uh, 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 (gasps) taking a deep breath, and you can't stop it. You know, it, it just, it just happens. Now, why? Well, we have to go back to the lung again. The lung has these 500 million alveoli, and they're very tiny. They're 200 microns across. So, they're really, really tiny. And you can think of them as fluid-filled. They're fluid lined, and the reason they're fluid lined has to do with the, um, esoterica of the mechanics of that. It makes it a little easier to stretch them with this fluid line, which is called surfactant. And surfactant is important during development that is a determining factor in the, uh, when premature infants are born. If they have not, do not have lung surfactant, it makes it much more challenging to take care of them than after they have lung surfactant, which is sometime, if I remember correctly, in the late second, early third trimester which it appears. In any case, it's fluid lined. Now, think of a balloon that you would blow up, but now before you blow it up, fill the balloon with water. Squeeze all the water out, and now, hold... When you squeeze all the water out, you notice the sides 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... or you'll notice if you've ever done it before, that the balloon is a little harder to inflate than if it were dry on the inside. Why is that? Because you have to overcome that surface tension. Well, your alveoli 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 an alveolus 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, but if they keep collapsing, you can lose a significant part of the surface area of your lung. Now, a normal breath is not enough to pop them open, but if you take (gasps) a deep breath, it pops 'em open.

    3. AHAndrew Huberman40:28

       Through nose, through nose or mouth?

    4. JFDr. Jack Feldman40:31

       It just increased that lung volume 'cause you're just pulling on the lungs. They'll pop open about every five minutes. Um, 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 put in these big steel tubes, and the way they would work is that the pressure outside the body would drop. That would put a expansion pressure on the, the lungs, excuse me, on the rib cage. The rib cage would expand, and then the lung would expand, and then the pressure would go back to normal and the lung and rib cage would go back to normal. There was a, this was great for getting ventilation, but there was a relatively high mortality rate. It was a bit of a mystery, and one solution was to just give bigger breaths. They gave bigger breaths when the mortality rate dropped, 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'd have one big breath. So, you have a couple of minutes of normal breaths and then one big breath, just mimicking the physiological size, and then the mortality rate drops significantly. And if you see someone on a vent- a ventilator in the hospital, if you watch every couple of minutes, you'll 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, uh, pressure to pop it open, it's the same thing with the alveoli. You need a bigger pressure, and a normal breath is not enough. So, you have to take a big inhale. (inhales) 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 want to, we asked is...... how is this happening? Why every five minutes? What's, what's doing it? And we g- got into it through a backdoor. Uh, typical of the way a lot of science gets done, there's a serendipitous, uh, uh, event where you run across a paper and something clicks and you just, you know, you, you follow it up. Sometimes you go down blind ends, but this turned out to be incredibly productive. Uh, one of the guys in my lab was reading a paper about stress, and during stress, lots of things happen in the body. One of which is that the hypothalamus, which is very reactive to body state, releases peptides, which are specialized molecules which then circulate throughout the brain and body to have particular effects, usually to help deal better with the stress. And one class of the peptides that are released are called bombesin-related peptides. And he also realized, because he was a breathing guy, that when you're stressed, you sigh more. So, we said, "All right, maybe they're related." Bombesin is relatively cheap to buy. We said, "Let's buy some bombesin and throw it in the brain stem. Let's see what happens." And, you know, they... one of the nice things about, uh, some experiments that we try to design is to fail quickly. So, here we had the idea. We throw bombesin in, and if bombesin did nothing, noth- nothing lost, maybe $50 to buy the bombesin. But if it did something, it might be of some interest. So, we... one afternoon, he did the experiment, and he comes to me. He says... I won't quote exactly what he said because that, uh, might, uh, need to be censored, but he said, "Look at this." And it was in a rat. Rats sigh about every two minutes. They're smaller than we are and they need to sigh more often. Their sigh rate from- went from 20 to 30 per hour to 500 per hour when you put bombesin into the preBotzinger complex.

    5. AHAndrew Huberman44:58

       Amazing.

    6. JFDr. Jack Feldman44:59

       And the way he did that is he took a very, very fine glass needle and anesthetize a rat and inserted that needle directly into the preBotzinger complex. So, it wasn't a generalized delivery of the peptide. It was localized to the preBotzinger, and (snaps fingers) the sigh rate went through the roof.

    7. AHAndrew Huberman45:20

       And I would, um, add that that was an important experiment to deliver the bombesin directly to that site because one could have concluded that the injection of the bombesin increased sighing because it increased stress rather than directly increased sighing.

    8. JFDr. Jack Feldman45:34

       Yeah, a- 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 was originating, we never could have done this experiment. And so, then we, then we did another experiment. We said, "Okay, what happens if we take the cells in the preBotzinger that are responding to the peptides?" So, neurons will respond to a peptide because they have specialized receptors for that peptide, and not every neuron expresses those receptors. In the preBotzinger complex, it's probably a few hundred out of thousands. So, we, uh, used the technique we had used before, and this was a technique d- developed by Doug Lappy down in San Diego, where you could take a peptide and conjugate it with a molecule called saporin. Saporin is a plant-derived molecule which is a cousin to ricin, and many of your listeners may have heard of ricin. Ricin-

    9. AHAndrew Huberman46:48

       It's a ribosomal toxin.

    10. JFDr. Jack Feldman46:49

        It, it's very nasty. It's, it... a, a single, you know, stab with an umbrella will kill you, which is a, uh, something that supposedly happened to a Bulgarian diplomat by a Russian operative on a bridge in London. He got stabbed. And the way ricin works is it goes inside a cell, crosses the cell membrane, goes inside the cell, kills the cell, then it goes to the next cell, and then the next cell, and then the next cell. It's, um, it's extremely, uh, dangerous. In fact, it's firstly impossible to work on in a lab in the United States. They won't let you-

    11. AHAndrew Huberman47:26

        Ricin?

    12. JFDr. Jack Feldman47:26

        ... touch it. Ricin.

    13. AHAndrew Huberman47:27

        'Cause, uh, we've worked with saporin many times.

    14. JFDr. Jack Feldman47:30

        Saporin is safe because it doesn't cross cell membranes. So, you get an injection of saporin, it won't do anything 'cause it stays outside of cells.

    15. AHAndrew Huberman47:39

        Please, nobody do that. Even though it doesn't (laughs) cross cell membranes, please, nobody inject saporin whether or not you are a-

    16. JFDr. Jack Feldman47:47

        (laughs)

    17. AHAndrew Huberman47:47

        ... operative or otherwise.

    18. JFDr. Jack Feldman47:49

        Thank you, Andrew, for protecting me there. Um, so, but what Doug Lappy figured out is that when a ligand binds to a receptor, that is when a molecule binds to its receptor, in many cases, that receptor ligand complex gets pulled inside the cell. So, it goes from the membrane of the cell inside the cell.

    19. AHAndrew Huberman48:13

        Sort of like you can't go to the dance alone, but if you're coupled up, you get in the door.

    20. JFDr. Jack Feldman48:17

        That's right. So, what he figured out is if you put saporin to the peptide, the peptide binds to its receptor, it gets internalized, and then when it's inside the cell, saporin does the same thing that ricin 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, ablated, are cells that express that receptor. So, if you have a big conglomeration of cells and you have a few thousand and only 50 of them res- express that receptor-... then you inject the safran conjugated to the ligand, to the peptide, and only those 50 cells die. (sniffs) So, we took bombesin conjugated to safran, injected in the preBotzinger complex of rats, and it took about (smacks lips) a couple of days for the safran to actually ablate cells, and what happened is that (sniffs) the mice started sighing less and less and l-, uh, excuse me, the rats started sighing less and less and less and less and essentially stopped sighing.

    21. AHAndrew Huberman49:26

        So, um, (smacks lips) your student, or post-doc was it, murdered these cells, and as a consequence the sighing goes away.

    22. JFDr. Jack Feldman49:36

        Right.

    23. AHAndrew Huberman49:36

        What was the consequence of eliminating

11. 49:39 – 1:00:42

    If We Don’t Sigh, Our Lung (& General) Health Suffers

    1. AHAndrew Huberman49:39

       sighing on the internal state or the behavior of the rats?

    2. JFDr. Jack Feldman49:44

       Uh-

    3. AHAndrew Huberman49:45

       Did they... In other words, if one can't sigh, generate physiological sighs, what is the consequence on state of mind? Uh, do... You would imagine that carbon dioxide would build up more readily or mo-, um, to higher levels in the bloodstream and that the animals would be more stressed. Tha- that's the kind of logical extension of the way we set it up.

    4. JFDr. Jack Feldman50:07

       Uh, it was less benign than that. When the animals got to the point where they weren't sighing, then... And we did not, uh, determine this but the presumption was that their lung function significantly deteriorated and their physio- their whole 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, um, uh, deteriorated that we sacrificed them at that point. Now, we don't know whether that is specifically related to the fact they didn't sigh or that it's, there was secondary damage due to the fact that some cells die, so we never determined that. Now, w- 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. (sniffs) And then I got a phone call from a graduate student at Stanford, Kevin Yakel, 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 lung in Drosophila, fruit flies, uh, Marc Krasnow.

    5. AHAndrew Huberman51:36

       Yeah.

    6. JFDr. Jack Feldman51:36

       And I said-

    7. AHAndrew Huberman51:37

       My nextdoor colleague.

    8. JFDr. Jack Feldman51:38

       Right.

    9. AHAndrew Huberman51:38

       Yeah.

    10. JFDr. Jack Feldman51:38

        And I said, "Why are you asking me this?" And he said, (laughs) "I was an undergraduate at UCLA and you gave a lecture in, 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, uh, something you really affected the life of a student.

    11. AHAndrew Huberman51:56

        Well, then you birthed a competitor but you had only yourself to blame.

    12. JFDr. Jack Feldman51:59

        No, I, I don't look at that as a competitor. I g- 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."

    13. AHAndrew Huberman52:12

        No one I ever trained with said that. It's o- it's open field. You want to work on something, you, you hop in the mix.

    14. JFDr. Jack Feldman52:17

        Yeah, yeah. And, um, but there, there are people like that, uh, neuroscientists like that. I never felt like that-

    15. AHAndrew Huberman52:22

        I, I hear that their breathing apparati are disrupted and it causes a brain dysfunction that leads to the behavior just, just described. It's actually not true.

    16. JFDr. Jack Feldman52:29

        (smacks lips) Um, um, so-

    17. AHAndrew Huberman52:31

        Um, but, but in terms of the... So, eh, I, I, the, uh, before, eh, you, we talk about the, the beautiful story with, with Yakel and Krasnow and Phelp, um, I want to just make sure that I understand. So, if physiological sighs don't happen, basically breathing overall suffers?

    18. JFDr. Jack Feldman52:54

        Well, that, that would go back to the observations in, uh, polio victims in these iron lungs where the principal deficit was there was no s- hi- hyperinflation of the lungs and they, many of them deteriorated and died.

    19. AHAndrew Huberman53:08

        Um, and just to stay on this one more moment before, uh, uh, 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. So barbiturates, alcohol combined with barbiturates is a common cause of death, uh, for drug users and, um, contraindications of drugs and these kinds of things. You hear all the time about celebrities dying because they combined alcohol with barbiturates. Is there any evidence that the sighs that occur during sleep or during states of, you know, deep, deep, um, uh, relaxation, um, and, and sedation, that sighs recover the, the brain? Because, uh, you could imagine that if the sighs don't happen as a consequence of some drug impacting these brain centers, that that could be one cause of basically asphyxiation and death.

    20. JFDr. Jack Feldman54:02

        W- if you look at the progression of any mammal to death, you find that their breathing slows down, uh, uh, uh, a death due to, quote, "natural causes." Their breathing slows down. It s- will stop and then they'll gasp, so we have the phrase dying gasp, the (gasps) super large breaths. Um, they're often described as an attempt to autoresuscitate, that is you take that super deep breath and that maybe it can kickstart the engine again. We do not know the degree to such things as gasps are really sighs that are particularly large, and so if you suppress the ability to gasp in an individual who is subject to an overdose then-...whereas they might been able to re-arouse their breathing, if that's prevented, they don't get re-aroused. So, that is certainly a, a possibility. Um, but this has not been investigated. I mean, one of the things that I'm interested in is in individuals who have, um, diseases which will affect pre-Botzinger complex. And there's, there's data in Parkinson's disease and multiple system atrophy, which is another form of neurodegeneration, where there's loss of neurons in pre-Botzinger. And the question is- and it also may happen in ALS, sometimes referred to as Lou Gehrig's disease, amyotrophic lateral sclerosis. These individuals often die during sleep. We have an idea that we have not been able to get anyone to test is that patients with Parkinson's, patients with MLS typically breathe normally during wakefulness. The disturbances that they have in breathing is during sleep. So, Parkinson's patients at the end stages of s- 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.

    21. AHAndrew Huberman56:42

        Wow.

    22. JFDr. Jack Feldman56:42

        And that resuscitation may or may not be due to an explicit suppression of SIAHs, but to an overall suppression of the whole apparatus of the pre-Botzinger complex.

    23. AHAndrew Huberman56:54

        Got it. Thank you. So, Yakel calls you up?

    24. JFDr. Jack Feldman56:59

        So, he calls us, calls me up-

    25. AHAndrew Huberman57:01

        Mm-hmm.

    26. JFDr. Jack Feldman57:01

        ...and he's g- g- great kid, s- super smart, and he tells me about these e- these experiments that he's doing where he's looking in 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 in one of these databases to see what's enriched. And I said, "That's great. Would you be willing to sort of share our work together?" And he says, "N- n- no. I have, my advisor doesn't want me to do that." So, I said, "Okay." But Kevin's a great kid and I enjoyed talking to him, and he's a smart guy, and you know, what I found, uh, in academia and, is that the smartest people only want to hire people smarter than them, and only want to int- and have the preference to interact with people smarter than them. The a- a- the faculty who are not at the highest level, and at every institution there's a distribution.

    27. AHAndrew Huberman58:12

        Yeah.

    28. JFDr. Jack Feldman58:12

        There are points above the mean and those below the mean. Those whom below the mean are very threatened by that. And, um, I saw Kevin as like a, 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 would, I did whatever I can to help, 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 head of the training program for neurologists at Stanford, and he invited me. And at the end of my visit, I go to Mark Krasnow's office, and Kevin is there and a post-doc, Peng Li, who was also working on a project was there. And towards the end of the conversation, um, the, uh, Mark says to me, "You know, we found this one molecule which is highly concentrated in a important region for breathing." And I said, "Oh, that's great. What is it?" And he says, "I can't tell you because we want to work on it." So, um, of course I'm disappointed, but I realized that, uh, s- and, uh, the ethic in some areas of science or the custom in some areas of science is that until you get a publication, you be relatively restricted in sharing information.

    29. AHAndrew Huberman59:42

        Mark and I are gonna have a chat when I come back.

    30. JFDr. Jack Feldman59:44

        Okay. All right.
12. 1:00:42 – 1:05:34

    Breathing, Brain States & Emotions

    1. AHAndrew Huberman1:00:42

       Kevin Yakel is spectacular. Uh, has his own lab at UCSF, and the work that I'm familiar with, uh, from Kevin is, is worth mentioning now, um, or I'll, I'll ask you to, to mention it, which is this reciprocal 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. Uh, 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. W- what is the relationship between brain state and breathing? And if you would, because I know you have a particular, um, love of, of one particular aspect of this, what is the relationship between brain rhythms, oscillations if you will, and breathing?

    2. JFDr. Jack Feldman1:01:47

       This is a topic which has really intrigued me over the past decade. I would say before that, I was, uh, in my silo, just interested about how the rhythm of breathing is generated and didn't really pay much attention to this other stuff. (smacks lips) For some reason, I got interested in it, uh, and I think it was triggered by an article in The New York Times about mindfulness. Now, believe it or not, although I had lived in California for 20 years at that time, I'd never heard of 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." 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, um, 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? Um, you know, we have a motto 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 tried. And I should tell you now, I still haven't done it yet, but I haven't given up-

    3. AHAndrew Huberman1:03:11

       Yet.

    4. JFDr. Jack Feldman1:03:11

       ... yet. I haven't given up. Um, so I, 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, uh, move your index finger to the same effect, but I really be- believed that the breathing part was involved. Now, I'm not an unbiased observer, so, uh, question is how can I demonstrate that? I didn't feel competent to do experiments in humans and I didn't feel like I'd design 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, but if we can, then we can actually study how this happens." So, believe it or not, I was able to get a, um, sort of a starter grant, an R21 from NCCIH. That's the National Complementary, uh, Medicine Institute.

    5. AHAndrew Huberman1:04:25

       A wonderful institute, I should mention. Our government puts major tax dollars toward studies of things like meditation, breath work, supplements, herbs, acupuncture. Uh, this is, I think, not well-known and it's an incredible thing that this, that our government does that, and I think it deserves a nod and more funding. (laughs)

    6. JFDr. Jack Feldman1:04:49

       Uh, I, I totally agree with you. I think that it's the kind of thing that many of us, including many neuro- many scientists thinks is too woo-woo and, and unsubstantiated, but we're learning more and more. You know, we used to laugh at neuroimmunology, that the nervous system didn't have anything to do with the immune system, and, uh, pain 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- there's real nuggets to be learned here. So, they went out on a limb and they funded this particular project, and now I'm going to leap ahead because for three years, we threw stuff up against the wall that didn't work, and

13. 1:05:34 – 1:11:00

    Meditating Mice, Eliminating Fear

    1. JFDr. Jack Feldman1:05:34

       recently, we had a major breakthrough. We found a protocol by which we can get mice to breathe slowly, awake mice to breathe slowly. I won't tell you.

    2. AHAndrew Huberman1:05:48

       Normally, they don't breathe slowly.

    3. JFDr. Jack Feldman1:05:49

       No, no. In other words, whatever their normal breath is, 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.

    4. AHAndrew Huberman1:06:05

       Do they levitate?

    5. JFDr. Jack Feldman1:06:07

       We haven't measured that yet. (laughs) I would say, a priori, we haven't seen them floating to the top of their cage, but we haven't weighed them. Maybe they weigh less. You know, they... Maybe, you know, levitation is inv- is graded, and so maybe if you weigh less, it's sort of, uh, partial levitation. In any case, um, we then tested them and we had control animals, mice. We did e- 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 through a standard fear conditioning, which we did with my colleague, Michael Fanzolo, who's one of the real gurus of fear, and we measured... A standard test is to put, uh, mice in a condition where they're concerned they'll receive a shock and their response is 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 grade to describe, uh, w- uh, the validity of the test, but it's very valid. The mi- the control mice had a freezing time which was just the same as ordinary mice would have. The ones that went through our protocol froze much, much less. Ac- ac- according to Michael, the degree to which they w- showed less freezing was as much 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. (laughs) The problem we have now is the grant ran out of money, the post-doc working on it left, and now we have to try and piece together everything, and, um, but the data's spectacular.

    6. AHAndrew Huberman1:08:06

       Well, I think it's, um, 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, the benefits of doing rodent studies that you can get deep into mechanism, um, and for people that, um, might think, "Well, we've known that meditation has these benefits. Why do you need to get mechanistic science?" I think that, uh, one thing that's important for people to remember is that first of all, as many people as one might think, uh, are meditating out there or doing breath work, f- a far, far, far greater number of people are not, right? I mean, there's a, uh, m- the majority of people don't take any time to do dedicated breath work nor meditate. Um, so whatever can incentivize people would be, uh, 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, a practical effect. People say, "30 minutes a day, 20 minutes a day, once a week, twice a week." Same thing with breath work. Um, finding minimum or effective thresholds for changing neural circuitry is what I think is the holy grail of all these, uh, practices, and that's only gonna be determined by the sorts of mechanistic studies that you describe. So I, this is wonderful. I, I do hope the work gets completed and, um, we can talk about ways that, uh, uh, we can ensure that that happens, but, um-

    7. JFDr. Jack Feldman1:09:25

       But let me, let me add one thing to what you're saying, Andrew. One of, one of the con- uh, 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, uh, th- uh, the intervention is. And so, it's easy to say that the meditative response is a plac- has a big component which is the placebo effect. My mice don't believe in the placebo effect. And so, if we could show there's a bonafide effect in mice, 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. In mice, it's, it's a non-issue. So I think that, uh, that in of itself would be a enormous message to send.

    8. AHAndrew Huberman1:10:14

       Excellent, and indeed, uh, a better point. Um, I think a 30-minute-a-day meditation, um, i- in these mice, if I understand correctly, the meditation, we don't know what they're thinking about-

    9. JFDr. Jack Feldman1:10:28

       Oh, it was breath practice, really.

    10. AHAndrew Huberman1:10:28

        Right, so it's breath practice.

    11. JFDr. Jack Feldman1:10:30

        Right.

    12. AHAndrew Huberman1:10:30

        So there, 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 (laughs) do it anyway.

    13. JFDr. Jack Feldman1:10:40

        (laughs)

    14. AHAndrew Huberman1:10:40

        So, 30 minutes a day in which breathing is deliberately slowed or is slowed relative to their normal patterns of breathing. Got it. Um, what was the frequency of sighing during that, uh, 30 minutes?

    15. JFDr. Jack Feldman1:10:54

        Uh, uh, uh-

    16. AHAndrew Huberman1:10:54

        Unclear?

    17. JFDr. Jack Feldman1:10:54

        ... we don't know yet.

    18. AHAndrew Huberman1:10:55

        Okay.

    19. JFDr. Jack Feldman1:10:55

        Well, no, we have the data. We just, we're analyzing the data.

    20. AHAndrew Huberman1:10:58

        To be determined, uh, or to

14. 1:11:00 – 1:16:25

    Brain States, Amygdala, Locked-In Syndrome, Laughing

    1. AHAndrew Huberman1:11:00

       be announced at some point. So, uh, so the fear centers are altered in some way that creates, uh, a shorter fear response to a foot shock.

    2. JFDr. Jack Feldman1:11:10

       Right.

    3. AHAndrew Huberman1:11:11

       Um, 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?

    4. JFDr. Jack Feldman1:11:22

       Okay. So, this gets back to our prior conversation. I sort of went off on a tangent. (sniffs) Um, we, we need, I think we need to think separately of the effect of volitional changes of breathing on emotion versus the effect, um, um, the e- the effect of brain state on breathing. So the effect of brain state on breathing, like when you're stressed is a effect, uh, 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 that may ultimately be tied together. So there's a landmark paper published in the '50s where they stimulated in the amygdala of cats and depending (laughs) on where they stimulated, they got profound changes in breathing. There's like every pattern of breathing you could possibly imagine, they found a site in the amygdala which could produce that. So there's clearly a powerful descending effect coming from the am- uh, the amygdala, which is a major site for processing emotion, fear, stress, or 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 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 controlled muscles are transmitted. So the fibers coming from your motor cortex-... go down to this part of the, the brainstem, which is called the ventral pons, 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 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, are rostral, closer to... are not interrupted. In other words, the interruption is below that. They continue to breathe because the centers for breathing don't require that volitional command. In any case, they're below that, so they're, they're fine. So, these people continue to breathe. Normal intelligence, but they can't move. There's a great book called The Diving Bell and the Butterfly about a young man, um, who ha- this happens to, and he describes his life, and it's a real testament to human, the human condition that he's, does this. It's a remarkable book. It's a short book. A-

    5. AHAndrew Huberman1:14:27

       Did he write the book by blinking-

    6. JFDr. Jack Feldman1:14:28

       He wro-

    7. AHAndrew Huberman1:14:29

       ... to a translator?

    8. JFDr. Jack Feldman1:14:29

       He, he, he did it by blinking to his caretaker. Uh, it's pretty amazing. And there was a movie, which I've never seen, with Javier Bardem as the protagonist, uh, but the book I highly recommend as, uh, anyone to read. Um, so a colleague's studying an individual who had locked-in syndrome, and they, this patient breathed very robotically, (laughs) 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, (blows raspberry) nothing happened. Just the patient recognized the command, but couldn't change it. Then all of a sudden, the patient's breathing changed considerably and they said to their patient, "What happened?" They said, "You told a joke and I laughed." And they went back, and whenever they told a joke that the patient found funny, the patient's breathing pattern changed, and you know your breathing pattern when you laugh is (inhales sharply) , you know, you inhale and you go, "Ha, 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.

    9. AHAndrew Huberman1:15:51

       Yeah, well, I'll, I'm, I'll name them. Um, Eric Kandel-

    10. JFDr. Jack Feldman1:15:54

        For one.

    11. AHAndrew Huberman1:15:55

        ... has an inspiratory laugh.

    12. JFDr. Jack Feldman1:15:56

        Yeah.

    13. AHAndrew Huberman1:15:56

        He's famous for a (inhales sharply) as opposed to a (laughs) .

    14. JFDr. Jack Feldman1:16:00

        Exactly.

    15. AHAndrew Huberman1:16:00

        Yeah.

    16. JFDr. Jack Feldman1:16:01

        Exactly. So, the, it's very stereotyped, but it, it's maintained in these people who lose volitional control of breathing. So, there's an emotive component controlling your breathing which has nothing to do with your emis- uh, vi- uh, volitional control, and it goes down through a different pathway 'cause it's not disrupted by this locked-in syndrome. If you look at motor control

15. 1:16:25 – 1:19:00

    Facial Expressions

    1. JFDr. Jack Feldman1:16:25

       of the face, we have the volitional control of the face, but we also have motor cont- uh, uh, emotional control of the face, which most of us can't control. So, when we look at another person, we tend, w- we're able to read a lot about what their, 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, um, poker players. Well, now poker players, you know, have tells, but many of them now wear, you know, dark glasses because a lot of the tells you blink or whatnot.

    2. AHAndrew Huberman1:17:03

       Pupil size is a tell.

    3. JFDr. Jack Feldman1:17:04

       Pupil size, pupil size is a tell, um, which is an autonomic function, not a s- a s- a, um, skeletal muscle function. But we have these, all these skeletal muscles which we're controlling which give us away. I have the th- I've tried to get my imaging friends to image some of the great actors that we have in Los Angeles.

    4. AHAndrew Huberman1:17:27

       You mean brain imagers?

    5. JFDr. Jack Feldman1:17:28

       Brain imagers.

    6. AHAndrew Huberman1:17:29

       Yeah.

    7. JFDr. Jack Feldman1:17:29

       I'm sorry.

    8. AHAndrew Huberman1:17:29

       No, that's all right.

    9. JFDr. Jack Feldman1:17:30

       I, I mean, I, yeah, brain imagers, because I think when, when I s- tell y- ask you to smile, I could tell that you're not happy that you're smiling because I asked you to smile. I think any of us can tell-

    10. AHAndrew Huberman1:17:44

        I just think you're about to crack a joke, but we're (laughs) , we're old friends, so, you know. (laughs)

    11. JFDr. Jack Feldman1:17:48

        (laughs) No, I'm, I'm, uh, that, that, you know, when, when you see a picture, uh, like at a birthday or whatnot and say s- say, "Cheese," you could tell that at least half of the people are not happy they're saying, "Cheese." Whereas a great actor, when, when they're able to dissemble in the fact that they're sad or they're happy, you believe it. They're not faking it. It's like-

    12. AHAndrew Huberman1:18:11

        (laughs) .

    13. JFDr. Jack Feldman1:18:11

        ... 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 parts of their emotive control system that the rest of us don't have. Maybe they develop it through training and maybe not, but I think that this can be imaged, so I would like to get one of these great actors in a imager and have them go through that and then, then get a normal person and see whether or not they can emulate that, and I think you're gonna find big differences in the way they control this emotive thing. So, this emotive control of the, the facial muscles I think is in large part similar to your emotive control of breathing. So, there's that emotive control and there's that volitional control, and they're different. They're, they're different.

16. 1:19:00 – 1:29:40

    Locus Coeruleus & Alertness

    1. JFDr. Jack Feldman1:19:00

       Now, the, you asked me about the Yakel stuff. The Yakel paper had to do with ascending at the effect of breathing on emotion. What Kevin found was that there was a population of neurons in the preBotzinga complex that-... we're always looking to things that are projecting ultimately on motor neurons, he found a population of cells that projected to locus coeruleus. Locus coeruleus, excuse me, is one of those places in the brain that seem to go everywhere.

    2. AHAndrew Huberman1:19:34

       It's like a sprinkler system.

    3. JFDr. Jack Feldman1:19:35

       Exactly, exactly. And influence mood and, you know, you've had podcasts about this. I mean, there's a lot of stuff going on with the amygdala, so, excuse me, the locus coeruleus. So you get into the locus coeruleus, you can now spray information out throughout the entire brain. He found specific cells that projected from preBotzinger to locus coeruleus, and that these cells are inspiratory modulated. Now, it's been known for a long time, since the '60s, that if you look in the locus coeruleus of cats when they're awake, you find many neurons that have respiratory modulation. No one paid much attention to them. I mean, why, why bother? Not why bother paying attention, but why would the brain bother to have these inputs? So what Kevin did with, um, Lindsay Schwartz and Li- Li-Shun Loh's lab, is they killed, ablated those cells going to locus coeruleus from preBotzinger and the animals became calmer, and their EEG levels changed in ways that are indicative that they became calmer.

    4. AHAndrew Huberman1:20:49

       And as I recall, they didn't just become calmer, but they weren't really capable of high arousal states. They were kind of flat.

    5. JFDr. Jack Feldman1:20:57

       Hmm, I- I don't think we really pursued that in the paper. Um, and so we'd have to ask John Huguenard about that, but, uh, I don't-

    6. AHAndrew Huberman1:21:08

       He's on the other side of my lap, so we'll, we'll ask him.

    7. JFDr. Jack Feldman1:21:11

       Yeah.

    8. AHAndrew Huberman1:21:11

       But- but nonetheless, um, that beautifully illustrates how there is a bidirectional control, right, of-

    9. JFDr. Jack Feldman1:21:21

       Well, that's ascending.

    10. AHAndrew Huberman1:21:23

        ... emotion, emotion, well, no, the, the, the two, uh, the two stories of the locked-in, um, syndrome plus the Jakob paper shows that emotional states influence breathing and breathing influences emotional states, eh, which, uh, but you mentioned inspiration, which I always call inhalation, but people will, will fo- follow... No, no, that's fine. We'll, those are interchangeable. Um, people can follow that. Um, there are some interesting papers from Noam Sobol's group and from a number of other groups that w- as we inhale or right after we inhale, (inhales) the brain is actually more alert 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.

    11. JFDr. Jack Feldman1:22:07

        Um, maybe. I, I mean, I don't, I don't, I mean, Noam's work is great. Um, l- l- l- let me backtrack a bit because I'm, I want people to understand that when we're talking about breathing affecting emotion and cognitive state, it's not simply coming from preBotzinger. There are l- there are at least... Well, there are several other sites, and let me sort of desc- I need to sort of go through that. One is olfaction. So when you're breathing, normal, normal breathing, you're inhaling and exhaling. 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 a profound influence and projections through many parts of the brain. So there's a signal arising from this rhythmic moving of air in and out of the nose that's going into the brain that has contained in it a respiratory modulation. So that signal is there. The brain doesn't have to be using it, but when it's dis- you know, discriminating odor and whatnot, that's riding on a oscillation which is respiratory related. Another potential source is the vagus nerve. The vagus nerve is a major nerve which is containing afferents from all of the viscera.

    12. AHAndrew Huberman1:23:34

        Afferents just being, uh-

    13. JFDr. Jack Feldman1:23:35

        A signal-

    14. AHAndrew Huberman1:23:36

        ... signals to, yeah.

    15. JFDr. Jack Feldman1:23:37

        Yeah, signals from the viscera. It also has signals coming from the brainstem down which are called efferents, 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, the lung stretch.

    16. AHAndrew Huberman1:24:02

        These are baroreceptors. Oh, sorry, the, uh, eight, the, well, you-

    17. JFDr. Jack Feldman1:24:06

        They're pressure receptors.

    18. AHAndrew Huberman1:24:06

        We have another, like the, like the piezoresceptors of the, of this year's Nobel Prize, yeah.

    19. JFDr. Jack Feldman1:24:10

        Yeah, yeah. So they're responding to the expansion and relaxation of the lung, and so if you record from the vagus nerve, you'll see that there's a huge respiratory modulation 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 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 vagus nerve is playing a role in normal processing. Okay, let me, let me continue. Carbon dioxide and oxygen levels. Now, under normal circumstances your oxygen levels are fine 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.Um, I have a colleague, Alisha Morrett, who is working with patients who have, who are anxious and many of them hyperventilate, and as a result of that hyperventilation their carbon dioxide levels are low. And she has developed a therapeutic treatment where she trains these people to breathe slower and the br- 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 sort of as a continuous background, can change and if it's changed chronically we know that highly elevated levels of CO2 can produce panic attacks. Uh, and, uh, we don't know the degree to that so it gets exacerbated by people who get, who have a panic attack, the degree to which their ambient CO2 levels are affecting their degree of discomfort.

    20. AHAndrew Huberman1:26:42

        What about people who are, um, tend to be too calm, meaning they're, they're feeling sleepy, they, they're under-breathing as opposed to over-breathing. Is there any, uh, knowledge of what the status of CO2 is in their system?

    21. JFDr. Jack Feldman1:26:57

        I don't know, which doesn't mean there's no knowledge but I'm unaware, una- unaware but that's blissfully unaware. I have not looked at that literature so I don't know.

    22. AHAndrew Huberman1:27:07

        I mean, most people, um, or 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, um, under-stimulated or exhausted all the time, it's a, it's a complicated thing to measure. I mean, you can do it but it's not as straightforward.

    23. JFDr. Jack Feldman1:27:25

        Well, CO2 is easy to measure.

    24. AHAndrew Huberman1:27:27

        But in terms of the, sort of the measures for feeling, uh, fatigue, you know, they're in- they're somewhat indirect, whereas stress we can, we can get at pulse rates and HRV and things of that sort.

    25. JFDr. Jack Feldman1:27:37

        Well, imagine that these, uh, these devices that we're all wearing will soon be able to measure... well, now they can measure oxygen levels, oxygen saturation.

    26. AHAndrew Huberman1:27:45

        Which is amazing.

    27. JFDr. Jack Feldman1:27:46

        Yeah. Um, but oxygens, you know, will pretty much stay above 90% unless there's some pathology or you go to altitude. But CO2 levels vary quite a bit and CO- in fact, because they vary, 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. So, even a small change in your CO2 will have a significant effect on your ventilation. So, this is another thing that not only changes your ventilation but affects your brain state. Now, another thing that could affect, um, breathing pra- how breathing practice can affect your emotional state is simply the descending command, because breathing practice involves volitional control of your breathing and therefore there's a signal it's originating somewhere in your motor cortex. That is not, of course that's going to go down to pre-Botzinger, 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 that 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, the mechanism is occurring is that these breathing related oscillations in the brain, they are playing a role in signal processing and maybe should I talk a little bit about the role that oscillations may be playing in signal processing?

    28. AHAndrew Huberman1:29:34

        Definitely, but before you do I, I just want to, um, ask you a, uh, intermediate question. We've

17. 1:29:40 – 1:35:22

    Breath Holds, Apnea, Episodic Hypoxia, Hypercapnia

    1. AHAndrew Huberman1:29:40

       talked a lot about inhalation, inspiration, and exhalation. Um, what about breath holds? You know, in apnea for instance, uh, people are holding their breath whether or not it's conscious or, or unconscious, they're holding their breath. Uh, what's known about breath holds, um, in terms of how it might interact with brain state or oxygen 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, uh, looking at a mechanistic level, but I find it really interesting and even if there are no studies, uh, I'd love it if you'd care to speculate.

    2. JFDr. Jack Feldman1:30:20

       Well, one of the breath practices that intrigue me is where you basically hyperventilate for a minute and then hold your breath for as long as you can.

    3. AHAndrew Huberman1:30:29

       Tummo style, Wim Hof style.

    4. JFDr. Jack Feldman1:30:31

       Yeah, exactly.

    5. AHAndrew Huberman1:30:31

       We call it in the laboratory, because frankly before Tummo and before Wim, um, there, there, it was referred to as cyclic hyperventilation. So it's basically, (breathing heavily) right-

    6. JFDr. Jack Feldman1:30:45

       Exactly.

    7. AHAndrew Huberman1:30:45

       ...followed by a breath hold and that breath hold could be done with lungs full or lungs empty.

    8. JFDr. Jack Feldman1:30:49

       So, I had a long talk with some colleagues about what they might think the underlying mechanisms are, particularly for the breath hold, and there's certainly a com- I suddenly envision that there's a component with respect to the presence or absence of that rhythmicity in your cortex which is having effect, but the other thing with the hyperventilation, hypoventilation or the apnea, is your CO2 levels are going from low to high.

    9. AHAndrew Huberman1:31:23

       Anytime you're holding your breath.

    10. JFDr. Jack Feldman1:31:24

        Anytime you're holding your breath. Okay, and those are going to have a profound influence. Now, I have to talk about episodic hypoxia.... 'cause there's a lot of work going on, particularly with Gordon Mitchell at the University of Florida is doing some extraordinary work on episodic hypoxia.

    11. AHAndrew Huberman1:31:44

        (sniffs)

    12. JFDr. Jack Feldman1:31:44

        So, in the '80s, David Millhorn, uh, did some really intriguing work. If I ask you to hold your breath, to, excuse me. If I gave you a low oxygen mixture for a couple of minutes, your breathing level would go up 'cause you'd have, you, wouldn't, you want to have more oxygen-

    13. AHAndrew Huberman1:32:05

        You're starving for air.

    14. JFDr. Jack Feldman1:32:06

        Yeah.

    15. AHAndrew Huberman1:32:06

        Yeah.

    16. JFDr. Jack Feldman1:32:06

        No. You're starving for oxygen.

    17. AHAndrew Huberman1:32:07

        All right.

    18. JFDr. Jack Feldman1:32:08

        Okay? Um, 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 air again, your ventilation quickly relaxes back down to normal. If, on the other hand, I gave you three minutes of hypoxia, five minutes of normoxia, three minutes of hypoxia, five minutes of normoxia, three minutes of hypoxia, five minutes of normoxia-

    19. AHAndrew Huberman1:32:38

        Normoxia being normal?

    20. JFDr. Jack Feldman1:32:39

        Normal, normal air.

    21. AHAndrew Huberman1:32:41

        Normal breathing, yeah.

    22. JFDr. Jack Feldman1:32:41

        ... your ventilation goes up, down, up, down, up, down, up, down. 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.

    23. AHAndrew Huberman1:32:58

        Mm-hmm.

    24. JFDr. Jack Feldman1:32:58

        This was originally done in animals, but in humans all the time. It seems to have profound benefit on motor function and cognitive function.

    25. AHAndrew Huberman1:33:08

        In what direction?

Episode duration: 2:23:36