back to indexDr. Jack Feldman: Breathing for Mental & Physical Health & Performance | Huberman Lab Podcast #54
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, my guest is Dr. Jack Feldman.
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Dr. Jack Feldman is a distinguished professor
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of neurobiology at the University of California, Los Angeles.
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He is known for his pioneering work
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on the neuroscience of breathing.
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We are all familiar with breathing
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and how essential breathing is to life.
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We require oxygen,
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and it is only by breathing that we can bring oxygen
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to all the cells of our brain and body.
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However, as the work from Dr. Feldman and colleagues
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tells us, breathing is also fundamental
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to organ health and function
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at an enormous number of other levels.
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In fact, how we breathe, including how often we breathe,
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the depth of our breathing,
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and the ratio of inhales to exhales
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actually predicts how focused we are,
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how easily we get into sleep,
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how easily we can exit from sleep.
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Dr. Feldman gets credit for the discovery
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of the two major brain centers
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that control the different patterns of breathing.
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Today, you'll learn about those brain centers
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and the patterns of breathing they control
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and how those different patterns of breathing
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influence all aspects of your mental and physical life.
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What's especially wonderful about Dr. Feldman and his work
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is that it not only points to the critical role
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of respiration in disease, in health, and in daily life,
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but he's also a practitioner.
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He understands how to leverage particular aspects
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of the breathing process in order to bias the brain
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to be in particular states that can benefit us all.
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Whether or not you are a person
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who already practices breath work
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or whether or not you're somebody
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who simply breathes to stay alive,
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by the end of today's discussion,
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you're going to understand a tremendous amount
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about how the breathing system works
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and how you can leverage that breathing system
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toward particular goals in your life.
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Dr. Feldman shares with us
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his own particular breathing protocols that he uses,
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and he suggests different avenues for exploring respiration
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in ways that can allow you, for instance,
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to be more focused for work,
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to disengage from work in high stress endeavors,
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to calm down quickly.
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And indeed, he explains not only how to do that,
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but all the underlying science in ways that will allow you
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to customize your own protocols for your needs.
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All the guests that we bring on the Huberman Lab Podcast
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are considered at the very top of their fields.
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Today's guest, Dr. Feldman,
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is not only at the top of his field, he founded the field.
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Prior to his coming into neuroscience
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from the field of physics,
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there really wasn't much information
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about how the brain controls breathing.
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There was a little bit of information,
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but we can really credit Dr. Feldman and his laboratory
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for identifying the particular brain areas
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that control different patterns of breathing
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and how that information can be leveraged
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towards health, high performance, and for combating disease.
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So today's conversation,
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you're going to learn a tremendous amount
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from the top researcher in this field.
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It's a really wonderful and special opportunity
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to be able to share his knowledge with you.
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And I know that you're not only going to enjoy it,
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but you are going to learn a tremendous amount.
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Before we begin, I'd like to emphasize
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that this podcast is separate
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from my teaching and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science-related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Thesis.
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Thesis is a company that makes nootropics.
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Now I've talked before on the podcast and elsewhere
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about the fact that I don't really like the term nootropics,
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One quick mention before we dive
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into the conversation with Dr. Feldman.
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During today's episode,
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we discuss a lot of breath work practices.
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And by the end of the episode,
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all of those will be accessible to you.
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However, I'm aware that there are a number
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of people out there that want to go even further
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into the science and practical tools of breath work.
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And for that reason, I want to mention a resource to you.
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There is a cost associated with this resource,
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but it's a terrific platform
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for learning about breath work practices
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and for building a number of different routines
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that you can do or that you could teach.
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It's called Our Breath Work Collective.
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I'm not associated with the Breath Work Collective,
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but Dr. Feldman is an advisor to the group
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and they offer daily live guided breathing sessions
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and an on-demand library that you can practice anytime,
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free workshops on breath work.
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And these are really developed by experts in the field,
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including Dr. Feldman.
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So as I mentioned, I'm not on their advisory board,
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but I do know them in their work
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and it is of the utmost quality.
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So anyone wanting to learn or teach breath work
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could really benefit from this course, I believe.
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If you'd like to learn more,
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you can click on the link in the show notes
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or visit ourbreathcollective.com slash Huberman
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and use the code Huberman at checkout.
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And if you do that,
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they'll offer you $10 off the first month.
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Again, it's ourbreathcollective.com slash Huberman
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to access the Our Breath Collective.
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And now for my conversation with Dr. Jack Feldman.
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Thanks for joining me today.
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It's a pleasure to be here, Andrew.
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Yeah, it's been a long time coming.
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You're my go-to source for all things respiration.
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I mean, I breathe on my own,
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but when I want to understand how I breathe
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and how the brain and breathing interact,
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you're the person I call.
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Well, I'll do my best.
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As you know, there's a lot that we don't understand,
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which still keeps me employed and engaged,
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but we do know a lot.
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Why don't we start off by just talking about
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what's involved in generating breath?
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could you comment on some of the mechanisms
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for rhythmic breathing versus non-rhythmic breathing?
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Okay, so on the mechanical side,
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which is obvious to everyone,
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we want to have air flow in, inhale,
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and we need to have air flow out.
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And the reason we'd need to do this
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is because for body metabolism, we need oxygen.
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And when oxygen is utilized
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through the aerobic metabolic process,
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we produce carbon dioxide.
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And so we have to get rid of the carbon dioxide
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that we produce, in particular,
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because the carbon dioxide affects the acid-base balance
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of the blood, the pH.
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And all living cells are very sensitive
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to what the pH value is.
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So your body is very interested in regulating that.
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Regulating that pH.
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So we have to have enough oxygen for our normal metabolism,
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and we have to get rid of the CO2 that we produce.
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So how do we generate this air flow?
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Well, the air comes into the lungs.
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We have to expand the lungs.
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And as the lungs expand,
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basically it's like a balloon that you would pull apart,
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the pressure inside that balloon drops,
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and air will flow into the balloon.
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So we put pressure on the lung to pull it apart
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that lowers the pressure in the air sacs called alveoli,
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and air will flow in because pressure outside the body
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is higher than pressure inside the body
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when you're doing this expansion, when you're inhaling.
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What produces that?
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Well, the principal muscle is the diaphragm,
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which is sitting inside the body just below the lung.
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And when you want to inhale,
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you basically contract the diaphragm, and it pulls it down.
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And as it pulls it down,
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it's inserting pressure forces on the lung.
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The lung wants to expand.
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At the same time, the rib cage is gonna rotate up and out,
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and therefore expanding the cavity, the thoracic cavity.
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At the end of inspiration,
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under normal conditions when you're at rest,
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you just relax, and it's like pulling on a spring.
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You pull down a spring,
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and you let go, and it relaxes.
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So you inhale, and you exhale.
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Inhale, relax, and exhale.
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So the exhale is passive?
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At rest, it's passive.
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We'll get into what happens when you need to increase
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the amount of air you're bringing in
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because your ventilation,
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your metabolism goes up like during exercise.
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Now, the muscles themselves,
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skeletal muscles, don't do anything
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unless the nervous system tells them to do something.
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And when the nervous system tells them to do something,
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So there are specialized neurons in the spinal cord,
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and then above the spinal cord,
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the region called the brain stem,
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which go to respiratory muscles,
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in particular for inspiration, the diaphragm,
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and the external intercostal muscles in the rib cage,
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and they contract.
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So these respiratory muscles, these inspiratory muscles
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become active, and they become active for a period of time.
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Then they become silent, and when they become silent,
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the muscles then relax back to their original resting level.
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Where does that activity in these neurons
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that innervate the muscle, which are called motor neurons,
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where does that originate?
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Well, this was a question that's been bandied
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around for thousands of years,
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and when I was a beginning assistant professor,
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it was fairly high priority for me
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to try and figure that out,
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because I wanted to understand where this rhythm
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of breathing was coming from,
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and you couldn't know where it was coming from
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until you knew where it was coming from.
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I didn't phrase that properly.
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You couldn't understand how it was being done
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until you know where to look.
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So we did a lot of experiments,
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which I can go into detail,
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and finally found there was a region in the brain stem,
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that's once again this region sort of above the spinal cord,
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which was critical for generating this rhythm.
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It's called the pre-Butzinger complex,
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and we can talk about how that was named.
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This small site, which contains in humans
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a few thousand neurons, it's located on either side,
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and it works in tandem, and every breath begins
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with neurons in this region beginning to be active,
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and those neurons then connect ultimately
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to these motor neurons going to the diaphragm
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and to the external intercostals,
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causing them to be active and causing
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this inspiratory effort.
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When the neurons in the pre-Butzinger complex
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finish their burst of activity,
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then inspiration stops, and then you begin to exhale
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because of this passive recall of the lung and rib cage.
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Could I just briefly interrupt you
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to ask a few quick questions before we move forward
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in this very informative answer.
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The two questions are, is there anything known
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about the activation of the diaphragm
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and the intercostal muscles between the ribs
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as it relates to nose versus mouth breathing,
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or are they activated in the equivalent way
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regardless of whether or not someone is breathing
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through their nose or mouth?
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I don't think we fully have the answer to that.
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Clearly, there are differences
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between nasal and mouth breathing.
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At rest, the tendency is to do nasal breathing
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because the air flows that are necessary
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for normal breathing are easily managed
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by passing through the nasal cavities.
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However, when your ventilation needs to increase,
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like during exercise, you need to move more air,
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you do that through your mouth
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because the airways are much larger then,
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and therefore you can move much more air.
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But at the level of the intercostals and the diaphragm,
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their contraction is almost agnostic
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to whether or not the nose and mouth are open.
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Okay, so if I understand correctly,
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there's no reason to suspect that there are particular,
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perhaps even non-overlapping sets of neurons
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in pre-Butzinger area of the brainstem
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that trigger nasal versus mouth inhales?
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No, I would say that it's not
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that the pre-Butzinger complex is not concerned
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and cannot influence that,
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but it does not appear as if there's any modulation
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of whether or not it's where the air is coming from,
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whether it's coming through your nasal passages
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or through your mouth.
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Thank you, and then the other question I have
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is that these intercostal muscles between the ribs
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that move the ribs up and out, if I understand correctly,
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and the diaphragm, are those skeletal,
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or as the Brits would say, skeletal muscles,
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or smooth muscles?
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What type of muscle are we talking about here?
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As I said earlier, these are skeletal,
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I didn't say they were skeletal muscles,
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but they're muscles that need neural input
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You talked about smooth muscles.
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They're specialized muscles like we have in the gut
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and in the heart, and these are muscles that are capable
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of actually contracting and relaxing on their own.
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So the heart beats.
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It doesn't need neural input in order to beat.
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The neural inputs modulate the strength of it
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and the frequency, but they beat on their own.
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The skeletal muscles involved in breathing
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need neural input.
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Now, there are smooth muscles that have an influence
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on breathing, and these are muscles
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that are lining the airways,
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and so the airways have smooth muscle,
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and when they become activated,
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the smooth muscle can contract or relax,
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and when they contract inappropriately
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is when you have problems breathing like in asthma.
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Asthma is a condition where you get
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inappropriate constriction of the smooth muscles
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So there's no reason to think that in asthma
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that the pre-butsinger or these other neuronal centers
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in the brain that activate breathing,
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that they are involved or causal for things like asthma?
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As of now, I would say the preponderance of evidence
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is that it's not involved, but we've not really fully
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investigated that.
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Sorry to break your flow, but I was terribly interested
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in knowing answers to those questions,
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and you provided them, so thank you.
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Now, remind me again where I was in my...
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We were just landing in pre-butsinger,
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and we will return to the naming of pre-butsinger
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because it's a wonderful and important story, really,
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that I think people should be aware of,
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but maybe you could march us through the brain centers
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that you've discovered and others have worked on as well
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that control breathing, pre-butsinger
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as well as related structures.
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So when we discovered the pre-butsinger,
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we thought that it was the primary source
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of all rhythmic respiratory movements,
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both inspiration and expiration.
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The notion of a single source is like day or night.
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It's like they're all coming,
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they all have the same origin that the earth rotates
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and day follows night.
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And we thought that the pre-butsinger complex
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would be inhalation, exhalation.
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And then in a series of experiments we did
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in the early part of 2000, we discovered
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that there seemed to be another region
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which was dominant in producing expiratory movements,
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that is the exhalation.
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We had made a fundamental mistake
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with the discovery of the pre-butsinger
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not taking into account that at rest
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expiratory muscle activity or exhalation is passive.
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So if that's the case, a group of neurons
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that might generate active expiration,
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that is to contract the expiratory muscles
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like the abdominal muscles of the internal intercostals
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We just thought it wasn't there was coming from one place.
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But we got evidence that in fact
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it may have been coming from another place.
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And following up on these experiments,
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we discovered that there was a second oscillator
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and that oscillator is involved
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in generating what we call active expiration.
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That is this active.
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Yeah, or when you begin to exercise,
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you have to go, and actually move that air out.
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This group of cells, which is silent at rest,
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suddenly becomes active to drive those muscles.
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And it appears that it's an independent oscillator.
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When maybe you could just clarify for people
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what an oscillator is.
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Okay, an oscillator is something that goes in a cycle.
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So you can have a pendulum as an oscillator
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going back and forth.
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The earth is an oscillator because it goes around
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and it's day and night.
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Some people's moods are oscillating.
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And it depends how regular they are.
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You can have oscillators that are highly regular
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that are in a watch,
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or you can have those that are sporadic or episodic.
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Breathing is one of those oscillators
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that for life has to be working continuously, 24-7.
link |
It starts late in the third trimester
link |
because it has to be working when you're born
link |
and basically works throughout life.
link |
And if it stops, if there's no intervention
link |
beyond a few minutes, it will likely be fatal.
link |
What is this second oscillator called?
link |
Well, we found it in a region around the facial nucleus.
link |
So we initially, when this region was initially identified,
link |
we thought it was involved in sensing carbon dioxide.
link |
It was what we call a central chemoreceptor.
link |
That is, we want to keep carbon dioxide levels,
link |
particularly in the brain, at a relatively stable level
link |
because the brain is extraordinarily sensitive
link |
If there's a big shift in carbon dioxide
link |
to be a big shift in brain pH,
link |
to be a big shift in brain pH,
link |
and that'll throw your brain,
link |
if I can use the technical term, out of whack.
link |
And so you want to regulate that.
link |
And the way to regulate something in the brain
link |
is you have a sensor in the brain.
link |
And others basically identified
link |
that the ventral surface of the brainstem,
link |
that is the part of the brainstem that's on this side,
link |
was critical for that.
link |
And then we identified a structure
link |
that was near the trapezoid nucleus.
link |
It was not named in any of these neuroanatomical atlases.
link |
So we just picked the name out of the hat
link |
and we called it the retrotrapezoid nucleus.
link |
I should clarify for people,
link |
when Jack is saying trapezoid,
link |
it doesn't mean the trapezoid muscles.
link |
Trapezoid refers to the shape of this nucleus,
link |
this cluster of neurons.
link |
Para-facial makes me think that this general area
link |
is involved in something related to mouth or face.
link |
Is it an area rich with neurons
link |
controlling other parts of the face?
link |
Eye blinks, nose twitches, lip curls, lip smacks?
link |
If you go back in an evolutionary sense,
link |
and a lot of things that are hard to figure out
link |
begin to make sense when you look
link |
at the evolution of the nervous system,
link |
when control of facial muscles,
link |
going back to more primitive creatures,
link |
because they had to take things in their mouth for eating.
link |
So we call that the face sort of developed.
link |
The eyes were there, the mouth is there.
link |
These nuclei that contained the motor neurons,
link |
a lot of the control systems for them
link |
developed in the immediate vicinity.
link |
So if you think about the face,
link |
there's a lot of subnuclei around there
link |
that had various roles
link |
at various different times in evolution.
link |
And at one point in evolution,
link |
the facial muscles were probably very important
link |
in moving fluid in and out of the mouth
link |
and moving air in and out of the mouth.
link |
And so part of these many different subnuclei
link |
now seems to be in mammals
link |
to be involved in the control of expiratory muscles.
link |
But we have to remember that mammals are very special
link |
when it comes to breathing,
link |
because we're the only class of vertebrates
link |
that have a diaphragm.
link |
If you look at amphibians and reptiles,
link |
they don't have a diaphragm.
link |
And the way they breathe
link |
is not by actively inspiring and passively expiring.
link |
They breathe by actively expiring and passively inspiring
link |
because they don't have a powerful inspiratory muscle.
link |
And somewhere along the line, the diaphragm developed.
link |
And there are lots of theories about how it developed.
link |
I don't think it's particularly clear.
link |
There was something that you can find in alligators
link |
and lizards that could have turned into a muscle
link |
that was the diaphragm.
link |
The amazing thing about the diaphragm
link |
is that it's mechanically extremely efficient.
link |
And what do I mean by that?
link |
Well, if you look at how oxygen gets from outside the body
link |
into the bloodstream,
link |
the critical passage is across the membrane in the lung.
link |
It's called the alveolar capillary membrane.
link |
The alveolus is part of the lung
link |
and the blood runs through capillaries,
link |
which are the smallest tubes in the circulatory system.
link |
And at that point, oxygen can go from the air-filled alveolus
link |
I find that amazing.
link |
Even though it's just purely mechanical,
link |
the idea that we have these little sacs in our lungs,
link |
we inhale and the air goes in
link |
and literally the oxygen can pass into the bloodstream.
link |
Passes into the bloodstream.
link |
But the rate at which it passes
link |
will depend on the characteristics of the membrane,
link |
what the distance is between the alveolus
link |
and the blood vessel, the capillary.
link |
But the key element is the surface area.
link |
The bigger the surface area,
link |
the more oxygen that can pass through.
link |
It's entirely a passive process.
link |
There's no magic about making oxygen go in.
link |
Now, how do you pack a large surface area in a small chest?
link |
Well, you start out with one tube, which is the trachea.
link |
The trachea expands.
link |
Now you have two tubes.
link |
Then you have four tubes and it keeps branching.
link |
At some point, at the end of those branches,
link |
you put a little sphere, which is an alveolus.
link |
And that determines what the surface area is going to be.
link |
Now, you then have a mechanical problem.
link |
You have the surface area.
link |
You have to be able to pull it apart.
link |
So imagine you have a little square of elastic membrane.
link |
It doesn't take a lot of force to pull it apart.
link |
But now if you increase it by 50 times,
link |
you need a lot more force to pull it apart.
link |
So amphibians who were breathing,
link |
not by compressing the lungs
link |
and then just passively expanding it,
link |
weren't able to generate a lot of force.
link |
So they have relatively few branches.
link |
So if you look at the surface area
link |
that they pack in their lungs,
link |
relative to their body size,
link |
it's not very impressive.
link |
Whereas when you get to mammals,
link |
the amount of branching that you have
link |
is you have four to 500 million alveoli.
link |
If we were to take those four to five million alveoli-
link |
A hundred million.
link |
Four to five million.
link |
A hundred million.
link |
A hundred million, excuse me.
link |
And lay those out flat,
link |
what sort of surface area are we talking about?
link |
About 70 square meters,
link |
which is about a third the size of a tennis court.
link |
So you have a membrane inside of you,
link |
a third the size of a tennis court,
link |
that you actually have to expand every breath.
link |
And you do that without exerting much of a,
link |
you don't feel it.
link |
And that's because you have this amazing muscle,
link |
which because of its positioning,
link |
just by moving two thirds of an inch down,
link |
is able to expand that membrane enough
link |
to move air into the lungs.
link |
the volume of air in your lungs
link |
is about two and a half liters.
link |
Do we need to convert that to courts?
link |
It's about two and a half liters.
link |
When you take a breath,
link |
you're taking another 500 milliliters or half a liter.
link |
That's the size maybe a little of my fist.
link |
So you're increasing the volume by 20%,
link |
but you're doing that
link |
by pulling on this 70 square meter membrane.
link |
But that's enough to bring enough fresh air into the lung
link |
to mix in with the air that's already there,
link |
that the oxygen levels in your bloodstream
link |
goes from a partial pressure of oxygen,
link |
which is 40 millimeters of mercury,
link |
to 100 millimeters of mercury.
link |
So that's a huge increase in oxygen.
link |
And that's enough to sustain normal metabolism.
link |
So we have this amazing
link |
mechanical advantage by having a diaphragm.
link |
Do you think that our brains are larger
link |
than that of other mammals in part
link |
because of the amount of oxygen
link |
that we have been able to bring into our system?
link |
I would say a key step in the ability
link |
to develop a large brain
link |
that has a continuous demand for oxygen is the diaphragm.
link |
Without a diaphragm, you're an amphibian.
link |
And there's another solution to increasing oxygen uptake,
link |
which is the way birds breathe,
link |
but birds have other limitations
link |
and they still can't get brains as big as mammals have.
link |
So the brain utilizes maybe 20% of all the oxygen
link |
that we intake, and it needs it continuously.
link |
The brain doesn't want to be neglected.
link |
So this puts certain demands on breathing system.
link |
In other words, you can't shut it down for a while,
link |
which poses other issues.
link |
You're born and you have to mature.
link |
You have the small body, you have a small lung,
link |
you have a third plant rib cage,
link |
and now you have to develop into an adult,
link |
which has a stiffer rib cage.
link |
And so there are changes happening in your brain,
link |
in your body, where breathing,
link |
the neural control of breathing has to change on the fly.
link |
It's not like for things like vision,
link |
where you have the opportunity to sleep,
link |
and while you're sleeping,
link |
the brain is capable of doing things
link |
that are not easy to do during wakefulness,
link |
like the construction crew comes in during sleep.
link |
Breathing has been, the change of breathing
link |
has been described as trying to build an airplane
link |
while it's flying.
link |
Basically what Jack is saying is that
link |
respiration science is more complex
link |
and hardworking than vision science,
link |
which is a direct jab at me
link |
that some of you might've missed,
link |
but I definitely did not miss.
link |
And I appreciate that you always take the opportunity,
link |
like a good New Yorker,
link |
to give me a good, healthy intellectual jab.
link |
A question related to diaphragmatic breathing
link |
versus non-diaphragmatic breathing,
link |
because the way you describe it,
link |
the diaphragm is always involved,
link |
but over the years,
link |
whether it be for yoga class or a breath work thing,
link |
or you hear online that we should be breathing
link |
with our diaphragm,
link |
that rather than lifting our rib cage when we breathe
link |
and our chest, that it is healthier, in air quotes,
link |
or better somehow to have the belly expand when we inhale.
link |
I'm not aware of any particular studies
link |
that have really examined the direct health benefits
link |
of diaphragmatic versus non-diaphragmatic breathing.
link |
But if you don't mind commenting on anything you're aware of
link |
as it relates to diaphragmatic
link |
versus non-diaphragmatic breathing,
link |
whether or not people tend to be diaphragmatic breathers
link |
by default, et cetera,
link |
that would be, I think, interesting to a number of people.
link |
Well, I think by default, we are obligate diaphragm breathers.
link |
There may be pathologies where the diaphragm is compromised
link |
and you have to use other muscles,
link |
and that's a challenge.
link |
at rest, other muscles can take over,
link |
but if you need to increase your ventilation,
link |
the diaphragm is very important.
link |
It would be hard to increase your ventilation otherwise.
link |
Do you pay attention to whether or not
link |
you are breathing in a manner
link |
where your belly goes out a little bit as you inhale?
link |
Because I can do it both ways, right?
link |
I can inhale, bring my belly in,
link |
or I can inhale, push my diaphragm and belly out,
link |
not the diaphragm out, and that's interesting, right?
link |
Because it's a completely different muscle set
link |
Well, in the context of things like breath practice,
link |
I'm a bit agnostic about the effects
link |
of some of the different patterns of breathing.
link |
Clearly some are gonna work through different mechanisms
link |
and we can talk about that,
link |
but at certain level, for example,
link |
whether it's primarily diaphragm
link |
where you move your abdomen or not,
link |
I am agnostic about it.
link |
I think that the changes that breathing induces
link |
in emotion and cognition,
link |
I have different ideas about what the influence is,
link |
and I don't see that primarily
link |
as how which particular muscles you're choosing,
link |
but that just could be my own prejudice.
link |
Okay, and we will return to that
link |
as a general theme in a little bit.
link |
I wanna ask you about sighing.
link |
One of the many great gifts
link |
that you've given us over the years
link |
is an understanding of these things
link |
that we call physiological sighs.
link |
Could you tell us about physiological sighs,
link |
what's known about them,
link |
what your particular interest in them is,
link |
and what they're good for?
link |
Very interesting and important question.
link |
So everyone has a sense of what a sigh is.
link |
We certainly, when we're emotional in some ways,
link |
we're stressed, we're particularly happy,
link |
we'll take a, we'll sigh.
link |
It turns out that we're sighing all the time,
link |
and when I would ask people
link |
who are not particularly knowledgeable
link |
that haven't read my papers or James Nestor's book
link |
or listened to your podcast,
link |
they're usually off by two orders of magnitude
link |
about how frequently we sigh on the low side.
link |
In other words, they say once an hour,
link |
10 times a day, we sigh about every five minutes.
link |
And I would encourage anyone who finds that
link |
to be a unbelievable fact
link |
is to lie down in a quiet room and just breathe normally,
link |
just relax, just let go,
link |
and just pay attention to your breathing,
link |
and you'll find that every couple of minutes
link |
you're taking a deep breath and you can't stop it.
link |
You know, it just happens.
link |
Well, we have to go back to the lung again.
link |
The lung has these 500 million alveoli,
link |
and they're very tiny.
link |
They're 200 microns across.
link |
So they're really, really tiny.
link |
And you can think of them as fluid-filled.
link |
They're fluid-lined.
link |
And the reason they're fluid-lined
link |
has to do with the esoterica of the mechanics of that.
link |
It makes it a little easier to stretch them
link |
with this fluid line, which is called surfactant.
link |
And surfactant is important during development.
link |
It is a determining factor when premature infants are born.
link |
If they do not have lung surfactant,
link |
it makes it much more challenging to take care of them
link |
than after they have lung surfactant,
link |
which is sometime, if I remember correctly,
link |
in the late second, early third trimester, which it appears.
link |
In any case, it's fluid-lined.
link |
Now think of a balloon that you would blow up,
link |
but now before you blow it up, fill the balloon with water.
link |
Squeeze all the water out,
link |
and now when you squeeze all the water out,
link |
you notice the size of the balloons stick to each other.
link |
Well, that's because water has what's called surface tension
link |
and when you have two surfaces of water together,
link |
they actually tend to stick to each other.
link |
Now, when you try and blow that balloon up,
link |
you know that it, or you'll notice
link |
if you've ever done it before,
link |
that the balloon is a little harder to inflate
link |
than if we're dry on the inside.
link |
Because you have to overcome that surface tension.
link |
Well, your alveoli have a tendency to collapse.
link |
There's 500 million of them.
link |
They're not collapsing at a very high rate,
link |
but it's a slow rate that's not trivial.
link |
And when an alveolus collapses,
link |
it no longer can receive oxygen or take carbon dioxide out.
link |
It's sort of taken out of the equation.
link |
Now, if you have 500 million of them and you lose 10,
link |
no big deal, but if they keep collapsing,
link |
you can lose a significant part
link |
of the surface area of your lung.
link |
Now, a normal breath is not enough to pop them open,
link |
but if you take a deep breath, it pops them open.
link |
Through nose or mouth.
link |
It doesn't matter.
link |
It doesn't matter.
link |
Or it's just increased that lung volume
link |
because you're just pulling on the lungs.
link |
They'll pop open about every five minutes.
link |
And so we're doing it every five minutes
link |
in order to maintain the health of our lung.
link |
In the early days of mechanical ventilation,
link |
which was used to treat polio victims,
link |
who had weakness of their respiratory muscles,
link |
they'd be put in these big steel tubes.
link |
And the way they would work is that the pressure
link |
outside the body would drop.
link |
That would put a expansion pressure on the lungs,
link |
excuse me, on the rib cage.
link |
The rib cage would expand.
link |
And then the lung would expand.
link |
And then the pressure would go back to normal.
link |
And the lung and rib cage would go back to normal.
link |
There was a, this was great for getting ventilation,
link |
but there was a relatively high mortality rate.
link |
It was a bit of a mystery.
link |
And one solution was to just give bigger breaths.
link |
They gave bigger breaths and the mortality rate dropped.
link |
And it wasn't until, I think it was the 50s,
link |
where they realized that they didn't have to increase
link |
every breath to be big.
link |
What they needed to do is every so often
link |
they'd have one big breath.
link |
So you have a couple of minutes of normal breaths
link |
and then one big breath,
link |
just mimicking the physiological size.
link |
And then the mortality rate dropped significantly.
link |
And if you see someone on a ventilator in the hospital,
link |
if you watch, every couple of minutes
link |
that you see the membrane move up and down,
link |
every couple of minutes there'll be a super breath
link |
and that pops it open.
link |
So there are these mechanisms for these physiological size.
link |
So just like with the collapse of the lungs
link |
where you need a big pressure to pop it open,
link |
it's the same thing with the alveoli.
link |
You need a bigger pressure
link |
and a normal breath is not enough.
link |
So you have to take a big inhale.
link |
And what nature has done is instead of requiring us
link |
to remember to do it, it does it automatically.
link |
And it does it about every five minutes.
link |
And one of the questions we asked is,
link |
how is this happening?
link |
Why every five minutes?
link |
And we got into it through a back door.
link |
Typical of the way a lot of science gets done,
link |
there's a serendipitous event
link |
where you run across a paper and something clicks
link |
and you just, you know, you follow it up.
link |
Sometimes you go down blind ends
link |
but this turned out to be incredibly productive.
link |
One of the guys in my lab was reading a paper about stress
link |
and during stress, lots of things happen in the body.
link |
One of which is that the hypothalamus,
link |
which is very reactive to body state,
link |
releases peptides, which are specialized molecules
link |
which then circulate throughout the brain and body
link |
to have particular effects,
link |
usually to help deal better with the stress.
link |
And one class of the peptides that are released
link |
are called bombastin-related peptides.
link |
And he also realized because he was a breathing guy
link |
that when you're stressed, you sigh more.
link |
So we said, all right, maybe they're related.
link |
Bombastin is relatively cheap to buy.
link |
We said, let's buy some bombastin,
link |
throw it in the brainstem, let's see what happens.
link |
And, you know, one of the nice things about some experiments
link |
that we try to design is to fail quickly.
link |
So here we had the idea, we throw bombastin in
link |
and if bombastin did nothing,
link |
nothing lost, maybe $50 to buy the bombastin.
link |
But if it did something, it might be of some interest.
link |
So one afternoon he did the experiment
link |
and he comes to me, he says,
link |
I won't quote exactly what he said
link |
because it might need to be censored,
link |
but he said, look at this.
link |
And it was in a rat.
link |
Rats sigh about every two minutes.
link |
They're smaller than we are
link |
and they need to sigh more often.
link |
Their sigh rate went from 20 to 30 per hour
link |
to 500 per hour when he put bombastin
link |
into the pre-butts in the complex.
link |
And the way he did that is he took a very,
link |
very fine glass needle and anesthetized a rat
link |
and inserted that needle directly
link |
into the pre-butts in the complex.
link |
So it wasn't a generalized delivery of the peptide,
link |
it was localized to the pre-butts in there
link |
and the sigh rate went through the roof.
link |
And I would add that that was an important experiment
link |
to deliver the bombastin directly to that site
link |
because one could have concluded
link |
that the injection of the bombastin increased sighing
link |
because it increased stress
link |
rather than directly increase sighing.
link |
Amongst hundreds of other possible interpretations.
link |
So the precision here is very important
link |
and that goes back to what I said at the very beginning,
link |
knowing where this is happening
link |
allows you to do the proper investigations.
link |
If we didn't know where the inspiratory rhythm
link |
was originating, we never could have done this experiment.
link |
And so then we did another experiment.
link |
We said, okay, what happens if we take the cells
link |
in the pre-butts in there
link |
that are responding to the peptide?
link |
So neurons will respond to a peptide
link |
because they have specialized receptors for that peptide.
link |
And not every neuron expresses those receptors.
link |
In the pre-butts in a complex,
link |
it's probably a few hundred out of thousands.
link |
So we use the technique we had used before.
link |
And this is a technique developed by Doug Lappe
link |
down in San Diego, where you could take a peptide
link |
and conjugate it with a molecule called saprin.
link |
Saprin is a plant-derived molecule
link |
which is a cousin to ricin.
link |
And many of your listeners may have heard of ricin.
link |
It's a ribosomal toxin.
link |
A single stab with an umbrella will kill you,
link |
which is something that supposedly happened
link |
to a Bulgarian diplomat by a Russian operative
link |
on a bridge in London.
link |
And the way ricin works is it goes inside a cell,
link |
crosses the cell membrane, goes inside the cell,
link |
kills the cell, then it goes to the next cell,
link |
and then the next cell, and then the next cell.
link |
It's extremely dangerous.
link |
In fact, it's firstly impossible to work on in a lab
link |
in the United States.
link |
They won't let you touch a ricin.
link |
Because we've worked with saprin many times.
link |
Saprin is safe because it doesn't cross cell membranes.
link |
So you get an injection of saprin and won't do anything
link |
because it stays outside of cells.
link |
Please, nobody do that,
link |
even though it doesn't cross cell membranes.
link |
Please, nobody inject saprin,
link |
whether or not you are a operative or otherwise.
link |
Thank you, Andrew, for protecting me there.
link |
But what Doug Lappe figured out is that
link |
when a ligand binds to a receptor,
link |
that's when a molecule binds to its receptor,
link |
in many cases, that receptor ligand complex
link |
gets pulled inside the cell.
link |
So it goes from the membrane of the cell inside the cell.
link |
It's more like you can't go to the dance alone,
link |
but if you're coupled up, you get in the door.
link |
So what he figured out is he put saprin to the peptide.
link |
The peptide binds to its receptor.
link |
It gets internalized.
link |
And then when it's inside the cell,
link |
saprin does the same thing the ricin does.
link |
It kills the cell.
link |
But then it can't go into the next cell.
link |
So the only cells that get killed,
link |
or the more polite term, ablated,
link |
are cells that express that receptor.
link |
So if you have a big conglomeration of cells,
link |
and you have a few thousand,
link |
and only 50 of them express that receptor,
link |
then you inject the saprin conjugated to the ligand,
link |
to the peptide, and only those 50 cells die.
link |
So we took bombicin conjugated to saprin,
link |
injected in the pre-butzinger complex of rats,
link |
and it took about a couple of days for the saprin
link |
to actually ablate cells.
link |
And what happened is that the mice started sighing
link |
less and less, excuse me, the rats started sighing less
link |
and less and less and less, and essentially stopped sighing.
link |
So your student, or postdoc was it,
link |
murdered these cells, and as a consequence,
link |
the sighing goes away.
link |
What was the consequence of eliminating sighing
link |
on the internal state or the behavior of the rats?
link |
In other words, if one can't sigh,
link |
generate physiological sighs,
link |
what is the consequence on state of mind?
link |
You would imagine that carbon dioxide
link |
would build up more readily,
link |
or to higher levels in the bloodstream,
link |
and that the animals would be more stressed.
link |
That's the kind of logical extension
link |
of the way we set it up.
link |
It was less benign than that.
link |
When the animals got to the point where they weren't sighing,
link |
then, and we did not determine this,
link |
but the presumption was that their lung function
link |
significantly deteriorated, and their whole health
link |
deteriorated significantly, and we had to sacrifice them.
link |
So I can't tell you whether they were stressed or not,
link |
but their breathing got to be significantly
link |
deteriorated that we sacrificed them at that point.
link |
Now, we don't know whether that is specifically related
link |
to the fact they didn't sigh,
link |
or that there was secondary damage
link |
due to the fact that some cells die,
link |
so we never determined that.
link |
Now, after we did this study, to be candid,
link |
it wasn't a high priority for us
link |
to get this out the door and publish it,
link |
so it stayed on the shelf.
link |
Then I got a phone call from a graduate student
link |
at Stanford, Kevin Yackel, who starts asking me
link |
all these interesting questions about breathing,
link |
and I'm happy to answer them, but at some point,
link |
it concerned me because he was working
link |
for a renowned biochemist who worked on lung and Drosophila,
link |
fruit flies, Mark Krasnow.
link |
Yeah, got my next door colleague.
link |
Right, and I said, why are you asking me this?
link |
And he said, I was an undergraduate at UCLA,
link |
and you gave a lecture in my undergraduate class,
link |
and I was curious about breathing ever since.
link |
So that's one of those things which, as a professor,
link |
you love to hear, that actually is something
link |
you really affected the life of a student.
link |
Well, and you birthed a competitor,
link |
but you had only yourself to blame.
link |
No, I don't look at that as a competitor.
link |
I think that there's enough interesting things to go on.
link |
I know some of our neuroscience colleagues say,
link |
you can work on my lab, but then when you leave my lab,
link |
you got to work on something different.
link |
No one I ever trained with said that.
link |
You want to work on something, you hop in the mix.
link |
But there are people like that, neuroscientists like that.
link |
I never felt like that.
link |
I hear that their breathing apparatus are disrupted,
link |
and it causes a brain dysfunction
link |
that leads to the behavior you just described.
link |
That's actually not true.
link |
Not true, but in terms of the,
link |
so before we talk about the beautiful story
link |
with Yackel and Krasnow and Feld lab,
link |
I want to just make sure that I understand.
link |
So if physiological sighs don't happen,
link |
basically breathing overall suffers.
link |
Well, that would go back to the observations
link |
and polio victims in these iron lungs
link |
where the principle deficit was
link |
there was no hyperinflation of the lungs
link |
and many of them deteriorated and died.
link |
And just to stay on this one more moment
link |
before we move to what you were about to describe,
link |
we hear often that people will overdose
link |
on drugs of various kinds because they stop breathing.
link |
So barbiturates, alcohol combined with barbiturates
link |
is a common cause of death for drug users
link |
and contraindications of drugs and these kinds of things.
link |
You hear all the time about celebrities dying
link |
because they combined alcohol with barbiturates.
link |
Is there any evidence that the sighs
link |
that occur during sleep or during states
link |
of deep, deep relaxation and sedation
link |
that sighs recover the brain?
link |
Because you could imagine that if these sighs don't happen
link |
as a consequence of some drug impacting these brain centers,
link |
that that could be one cause
link |
of basically asphyxiation and death.
link |
If you look at the progression of any mammal to death,
link |
you find that their breathing slows down,
link |
a death due to quote natural causes.
link |
Their breathing slows down, it will stop
link |
and then they'll gasp.
link |
So we have the phrase dying gas, super large breaths.
link |
They're often described as an attempt to auto resuscitate.
link |
That is you take that super deep breath
link |
and that maybe it can kickstart the engine again.
link |
We do not know the degree to such things as gas
link |
are really sighs that are particularly large.
link |
And so if you suppress the ability to gasp
link |
in an individual who is subject to an overdose,
link |
then whereas they might been able
link |
to re-arouse their breathing,
link |
if that's prevented, they don't get re-aroused.
link |
So that is certainly a possibility.
link |
But this has not been investigated.
link |
I mean one of the things that I'm interested in
link |
is in individuals who have
link |
diseases which will affect pre-Butzinger complex.
link |
And there's data in Parkinson's disease
link |
and multiple system atrophy,
link |
which is another form of neurodegeneration
link |
where there's loss of neurons in pre-Butzinger.
link |
And the question is, and it also may happen in ALS,
link |
sometimes referred to as Lou Gehrig's disease,
link |
and mitral foot glottal sclerosis.
link |
These individuals often die during sleep.
link |
We have an idea that we have not been able
link |
to get anyone to test is that
link |
patients with Parkinson's, patients with MLS,
link |
typically breathe normally during wakefulness.
link |
The disturbances that they have in breathing
link |
So Parkinson's patients at the end stages of the disease
link |
often have significant disturbances in their sleep pattern,
link |
but not during wakefulness.
link |
And we think that what could be happening
link |
is that the proximate cause of death
link |
is not heart failure, is that they become apneic,
link |
they stop breathing and don't resuscitate.
link |
And that resuscitation may or may not be due
link |
to an explicit suppression of size,
link |
but to an overall suppression of the whole apparatus
link |
of the pre-Butzinger complex.
link |
Got it, thank you.
link |
So Yackel calls you up.
link |
So he calls me up and he's great kids, super smart,
link |
and he tells me about these experiments that he's doing
link |
where he's looking at a database
link |
to try and find out what molecules are enriched
link |
in regions of the brain that are critical for breathing.
link |
So we and others have mapped out these regions
link |
in the brain stem, and he was looking
link |
at one of these databases to see what's enriched.
link |
And I said, that's great.
link |
Would you be willing to sort of share our work together?
link |
He says, no, my advisor doesn't want me to do that.
link |
But Kevin's a great kid and I enjoyed talking to him
link |
and he's a smart guy.
link |
And you know, what I found in academia
link |
and is that the smartest people
link |
only wanna hire people smarter than them
link |
and only wanna have the preference
link |
to interact with people smarter than them.
link |
The faculty who are not at the highest level
link |
and at every institution there's a distribution,
link |
the ones above the mean and those below the mean,
link |
those who are below the mean are very threatened by that.
link |
And I saw Kevin as like a shining light
link |
and I didn't care whether he was gonna out-compete me
link |
because whatever he did was gonna help me in the field.
link |
So I did whatever I can to help, to work with Kevin.
link |
So at one point I got invited
link |
to give grand rounds of neurology at Stanford.
link |
Turns out an undergraduate student who had worked with me
link |
was now head of the training program
link |
for neurologists at Stanford and he invited me.
link |
And at the end of my visit,
link |
I go to Mark Krausner's office and Kevin is there
link |
and a postdoc Pungley who was also working on a project
link |
was there and towards the end of the conversation,
link |
you know, we found this one molecule
link |
which is highly concentrated
link |
in an important region for breathing.
link |
I said, oh that's great, what is it?
link |
And he says, I can't tell you
link |
because we wanna work on it.
link |
So of course I'm disappointed
link |
but I realized that the ethic in some areas of science
link |
or the custom in some areas of science
link |
is that until you get a publication,
link |
you'll be relatively restricted in sharing information.
link |
Mark and I are gonna have a chat when I get back.
link |
Well he may remember the story differently
link |
And as I'm walking out the door,
link |
I remember these experiments I described to you
link |
about Bombesan and that was the only unusual molecule
link |
So the reason I'm rushing out the door
link |
is I have a flight to catch.
link |
So I stick my head in, I said,
link |
is this molecule related to Bombesan?
link |
And then I run off, I don't even wait for them to reply.
link |
I get to the airport, Mark calls me and he says,
link |
Bombesan, the peptide we found is related to Bombesan,
link |
And I said, I'm not telling.
link |
Oh my, I'm so glad I wasn't involved in this collaboration.
link |
No, no, but that was sort of a tease
link |
because I said, well, let's work together on this.
link |
And then we worked together on this.
link |
It was a prisoner's dilemma at that point, yeah.
link |
So Kevin Yackel is spectacular,
link |
has his own lab at UCSF.
link |
And the work that I'm familiar with from Kevin
link |
is worth mentioning now, or I'll ask you to mention it,
link |
which is this reciprocal relationship between brain state,
link |
or we could even say emotional state and breathing.
link |
And I'd love to get your thoughts on how breathing interacts
link |
with other things in the brain.
link |
You've beautifully described how breathing controls
link |
the lungs, the diaphragm and the interactions
link |
between oxygen and carbon dioxide and so forth.
link |
But as we know, when we get stressed,
link |
our breathing changes.
link |
When we're happy and relaxed, our breathing changes.
link |
But also if we change our breathing,
link |
we in some sense can adjust our internal state.
link |
What is the relationship between brain state and breathing?
link |
And if you would, because I know you have a particular love
link |
of one particular aspect of this,
link |
what is the relationship between brain rhythms,
link |
oscillations, if you will, and breathing?
link |
This is a topic which has really intrigued me
link |
over the past decade.
link |
I would say before that, I was in my silo,
link |
just interested about how the rhythm of breathing
link |
is generated and didn't really pay much attention
link |
to this other stuff.
link |
For some reason, I got interested in it.
link |
And I think it was triggered by an article
link |
in the New York Times about mindfulness.
link |
Now, believe it or not, although I'd lived in California
link |
for 20 years at that time, I never heard of mindfulness.
link |
It's staggering how isolated you can be from the real world.
link |
And I Googled it, and there was a mindfulness institute
link |
at UCLA, and they were giving courses in meditation.
link |
So I said, oh, this is great because I can now see
link |
whether or not the breathing part of meditation
link |
has anything to do with the purported effects of meditation.
link |
So I signed up for the course.
link |
And as I joked to you before, I had two goals.
link |
One was to see whether or not breathing had an effect,
link |
and the other was to levitate.
link |
Because I grew up with all these kung fu things,
link |
and all the monks could levitate when they meditated.
link |
We have a model in the lab.
link |
You can't do anything interesting
link |
if you're afraid of failing.
link |
And if I fail to levitate, well, at least I tried.
link |
And I should tell you now, I still haven't done it yet,
link |
but I haven't given up yet.
link |
I haven't given up.
link |
So I took this course in mindfulness,
link |
and it became apparent to me that the breathing part
link |
was actually critical.
link |
It wasn't simply a distraction or a focus.
link |
They could have had you move your index finger
link |
to the same effect.
link |
But I really believed that the breathing part was involved.
link |
Now, I'm not an unbiased observer,
link |
so the question is, how can I demonstrate that?
link |
I didn't feel competent to do experiments in humans,
link |
and I didn't feel like I designed
link |
the right experiments in humans,
link |
but I felt maybe I can study this in rodents.
link |
So we got this idea that we're gonna teach rodents
link |
And that's laughable, but we said,
link |
but if we can, then we can actually study how this happens.
link |
So believe it or not,
link |
I was able to get a sort of a starter grant,
link |
an R21 from NCCIH.
link |
That's the National Complementary Medicine Institute.
link |
A wonderful institute I should mention.
link |
Our government puts major tax dollars
link |
toward studies of things like meditation, breath work,
link |
supplements, herbs, acupuncture.
link |
This is, I think, not well known,
link |
and it's an incredible thing
link |
that our government does that,
link |
and I think it deserves a nod and more funding.
link |
I totally agree with you.
link |
I think that it's the kind of thing that many of us,
link |
including many scientists,
link |
thinks is too woo-woo and unsubstantiated.
link |
But for learning more and more,
link |
we used to laugh at neuroimmunology,
link |
that the nervous system didn't have anything
link |
to do with the immune system,
link |
and pain itself can influence your immune system.
link |
I mean, there are all these things that we're learning
link |
that we used to dismiss,
link |
and I think there's real nuggets to be learned here.
link |
So they went out on a limb
link |
and they funded this particular project.
link |
And now I'm gonna leap ahead because for three years,
link |
we threw stuff up against the wall that didn't work.
link |
And recently, we had a major breakthrough.
link |
We found a protocol by which we can get mice
link |
to breathe slowly, awake mice to breathe slowly.
link |
Normally, they don't breathe slowly.
link |
In other words, whatever their normal breath is,
link |
we could slow it down by a factor of 10,
link |
and they're fine doing that.
link |
So we could do that for,
link |
we did that 30 minutes a day for four weeks, okay?
link |
Like a breath practice.
link |
We haven't measured that yet.
link |
I would say a priori,
link |
we haven't seen them floating to the top of their cage,
link |
but we haven't weighed them.
link |
Maybe they weigh less.
link |
You know, maybe levitation is graded,
link |
and so maybe if you weigh less,
link |
it's sort of a partial levitation.
link |
In any case, we then tested them,
link |
and we had control animals, mice,
link |
where we did everything the same,
link |
except the manipulation we made
link |
did not slow down their breathing.
link |
So, but they went through everything else.
link |
We then put them through a standard fear conditioning,
link |
which we did with my colleague, Michael Fanzolo,
link |
who's one of the real gurus of fear.
link |
And we measured a standard test
link |
is to put mice in a condition
link |
where they're concerned that we receive a shock,
link |
and their response is that they freeze.
link |
And the measure of how fearful they are
link |
is how long they freeze.
link |
This is well validated,
link |
and it's way above my pay grade to describe
link |
the validity of the test, but it's very valid.
link |
The control mice had a freezing time,
link |
which was just the same as ordinary mice would have.
link |
The ones that went through our protocol
link |
froze much, much less.
link |
According to Michael,
link |
the degree to which they showed less freezing
link |
was as much as if there was a major manipulation
link |
in the amygdala, which is a part of the brain
link |
that's important in fear processing.
link |
It's a staggering change.
link |
The problem we have now is the grant ran out of money,
link |
the postdoc working on it left,
link |
and now we have to try and piece together everything,
link |
but the data is spectacular.
link |
Well, I think it's,
link |
I'll just pause you for a moment there,
link |
because I think that the,
link |
you know, you're talking about a rodent study,
link |
but I think the benefits of doing rodent studies
link |
that you can get deep into mechanism,
link |
and for people that might think,
link |
well, we've known that meditation has these benefits,
link |
why do you need to get mechanistic science?
link |
I think that one thing that's important
link |
for people to remember is that,
link |
first of all, as many people as one might think
link |
are meditating out there or doing breath work,
link |
a far, far, far greater number of people are not, right?
link |
I mean, the majority of people don't take any time
link |
to do dedicated breath work nor meditate.
link |
So whatever can incentivize people would be wonderful.
link |
But the other thing is that
link |
it's never really been clear to me
link |
just how much meditation is required for a real effect,
link |
meaning a practical effect.
link |
People say 30 minutes a day, 20 minutes a day,
link |
once a week, twice a week, same thing with breath work.
link |
Finding minimum or effective thresholds
link |
for changing neural circuitry
link |
is what I think is the holy grail of all these practices,
link |
and that's only going to be determined
link |
by the sorts of mechanistic studies that you describe.
link |
So this is wonderful.
link |
I do hope the work gets completed
link |
and we can talk about ways that,
link |
we can ensure that that happens, but-
link |
But let me add one thing to what you're saying, Andrew.
link |
One of the issues I think for a lot of people
link |
is that there's a placebo effect.
link |
That is, in humans, they can respond to something
link |
even though the mechanism has nothing to do
link |
with what the intervention is.
link |
And so it's easy to say that the meditative response
link |
has a big component which is a placebo effect.
link |
My mice don't believe in the placebo effect.
link |
And so if we could show there's a bona fide effect in mice,
link |
it is convincing in ways that no matter
link |
how many human experiments you did,
link |
the control for the placebo effect
link |
is extremely difficult in humans.
link |
In mice, it's a non-issue.
link |
So I think that that in of itself
link |
would be an enormous message to send.
link |
Excellent and indeed a better point.
link |
I think a 30-minute-a-day meditation in these mice,
link |
if I understand correctly, the meditation,
link |
we don't know what they're thinking about-
link |
Well, it's breath practice.
link |
Right, so it's breath practice.
link |
Because presumably they're not thinking
link |
about their third eye center, lotus position, levitation,
link |
whatever it is, they're not instructed as to what to do
link |
and if they were, they probably wouldn't do it anyway.
link |
So 30 minutes a day in which breathing
link |
is deliberately slowed or is slowed
link |
relative to their normal patterns of breathing.
link |
What was the frequency of sighing during that 30 minutes?
link |
Unclear. We don't know yet.
link |
Well, no, we have the data.
link |
We just, we're analyzing the data.
link |
To be determined or to be announced at some point.
link |
So the fear centers are altered in some way
link |
that creates a shorter fear response to a foot shock.
link |
What are some other examples that you are aware of
link |
from working in your laboratory
link |
or work in other laboratories for that matter
link |
about interactions between breathing
link |
and brain state or emotional state?
link |
So this gets back to a prior conversation
link |
I sort of went off on a tangent.
link |
We need, I think we need to think separately
link |
of the effect of volitional changes of breathing
link |
on emotion versus the effect,
link |
the effect of brain state on breathing.
link |
So the effect of brain state on breathing
link |
like when you're stressed is a effect
link |
or presumably originating in higher centers
link |
if I can use that term, affecting breathing.
link |
The reciprocal is that when you change breathing,
link |
it affects your emotional state.
link |
I think of those two things as different
link |
that may ultimately be tied together.
link |
So there's a landmark paper published in the 50s
link |
where they stimulated in the amygdala of cats
link |
and depending on where they stimulated,
link |
they got profound changes in breathing.
link |
There's like every pattern of breathing
link |
could possibly imagine they found a site in the amygdala
link |
which could produce that.
link |
So there's clearly a powerful descending effect
link |
coming from the amygdala, which is a major site
link |
for processing emotion, fear, stress and whatnot
link |
that can affect breathing.
link |
And clearly we have volitional control over breathing.
link |
So we have profound effects there.
link |
Now I should say about emotional control of breathing,
link |
I need to segue into talking about locked-in syndrome.
link |
Locked-in syndrome is a devastating lesion
link |
that happens in a part of the brainstem
link |
where signals that controlled muscles are transmitted.
link |
So the fibers coming from your motor cortex
link |
go down to this part of the brainstem
link |
which is called the ventral pons.
link |
And if there's a stroke there, it can damage these pathways.
link |
What happens in individuals who have locked-in syndrome
link |
is they lose all volitional movement
link |
except lateral movement of the eyes
link |
and maybe the ability to blink.
link |
The reason they're able to still blink and move their eyes
link |
is that those control centers are rostral,
link |
closer to, are not interrupted.
link |
In other words, the interruption is below that.
link |
They continue to breathe
link |
because the centers for breathing
link |
don't require that volitional command.
link |
In any case, they're below that.
link |
So these people continue to breathe.
link |
Normal intelligence, but they can't move.
link |
There's a great book called
link |
The Diving Bell and the Butterfly
link |
about a young man who this happens to
link |
and he describes his life.
link |
And it's a real testament to the human condition
link |
that he does this.
link |
It's a remarkable book.
link |
It's a short book.
link |
Did he write the book by blinking to the translator?
link |
He did it by blinking to his caretaker.
link |
It's pretty amazing.
link |
And there was a movie which I've never seen
link |
with Javier Bardin as the protagonist,
link |
but the book I highly recommend to anyone to read.
link |
So I had colleagues studying an individual
link |
who had locked-in syndrome.
link |
And this patient breathed very robotically.
link |
Totally consistent, very regular.
link |
They gave the patient a low oxygen mixture to breathe.
link |
Ventilation went up.
link |
A CO2 mixture to breathe, ventilation went up.
link |
So all the regulatory apparatus for breathing was there.
link |
They asked the patient to hold his breath
link |
or to breathe faster.
link |
Just the patient recognized the command,
link |
but couldn't change it.
link |
And all of a sudden the patient's breathing
link |
changed considerably.
link |
And they said to the patient, what happened?
link |
They said, you told a joke and I laughed.
link |
And they went back.
link |
Whenever they told a joke that the patient found funny,
link |
the patient's breathing pattern changed.
link |
And you know your breathing pattern when you laugh
link |
is you inhale, you go ha ha ha ha.
link |
But it's also very distinctive.
link |
We have some neuroscience colleagues who will go unnamed
link |
who if you heard them laugh 50 yards away,
link |
you know exactly who they are.
link |
Yeah, well, I'll name them.
link |
Eric Kandel for one has an inspiratory laugh.
link |
He's famous for a, as opposed to a ha ha.
link |
So it's very stereotyped,
link |
but it's maintained in these people
link |
who lose volitional control of breathing.
link |
So there's an emotive component controlling your breathing,
link |
which has nothing to do with your volitional control
link |
and it goes down to a different pathway
link |
because it's not disrupted by this locked-in syndrome.
link |
If you look at motor control of the face,
link |
we have the volitional control of the face,
link |
but we also have motor control,
link |
emotional control of the face,
link |
which most of us can't control.
link |
So when we look at another person,
link |
we tend, we're able to read a lot about
link |
what their emotional state is.
link |
And that's a lot about how primates communicate.
link |
Humans communicate.
link |
And you have people who are good deceivers,
link |
probably used car salesman, poker players,
link |
or now poker players have tells,
link |
but many of them now wear dark glasses
link |
because a lot of the tells you blink or whatnot.
link |
Pupil size is a tell.
link |
Pupil size, pupil size is a tell,
link |
which is an autonomic function,
link |
not a skeletal muscle function.
link |
But we have all these skeletal muscles
link |
which we're controlling, which give us away.
link |
I have, I've tried to get my imaging friends
link |
to image some of the great actors
link |
that we have in Los Angeles.
link |
You mean brain imagers.
link |
Brain imagers, I'm sorry.
link |
No, that's all right.
link |
I mean, yeah, brain imagers.
link |
when I tell, ask you to smile,
link |
I could tell that you're not happy,
link |
that you're smiling because I asked you to smile.
link |
I think anybody's that's right.
link |
That's a crack at joke, but we're old friends, so.
link |
No, I'm not, that when you see a picture
link |
like at a birthday or whatnot and say, say cheese,
link |
you could tell that at least half of the people
link |
are not happy they're saying cheese.
link |
Whereas a great actor,
link |
when they're able to dissemble
link |
in the fact that they're sad or they're happy,
link |
you believe it, they're not faking it.
link |
It's like, that's great acting.
link |
And I don't think everyone could do that.
link |
I think that the individuals who are able to do that
link |
have some connection to the parts
link |
of their emotive control system
link |
that the rest of us don't have.
link |
Maybe they develop it through training and maybe not,
link |
but I think that this can be imaged.
link |
So I would like to get one of these great actors
link |
in an imager and have them go through that
link |
and then get a normal person
link |
and see whether or not they can emulate that.
link |
And I think you're gonna find big differences
link |
in the way they control this emotive thing.
link |
So this emotive control of the facial muscles,
link |
I think is in large part
link |
similar to the emotive control of breathing.
link |
So there's that emotive control
link |
and there's that volitional control
link |
and they're different, they're different.
link |
Now, you asked me about the Yakl stuff.
link |
The Yakl paper had to do with ascending,
link |
that the effect of breathing on emotion.
link |
What Kevin found was that there was a population of neurons
link |
in the pre-Butzinger complex
link |
that we're always looking to things
link |
that are projecting ultimately emotive neurons.
link |
He found the population of cells
link |
that projected to locus coeruleus.
link |
Locus coeruleus, excuse me,
link |
is one of those places in the brain
link |
that seem to go everywhere.
link |
Take a sprinkler system.
link |
And influence mood.
link |
And, you know, you've had podcasts about this.
link |
I mean, there's a lot of stuff going on with the amygdala.
link |
So, excuse me, the locus coeruleus.
link |
So you get into the locus coeruleus,
link |
you can now spray information out
link |
throughout the entire brain.
link |
He found specific cells that projected
link |
from pre-Butzinger to locus coeruleus.
link |
And that these cells are inspiratory modulator.
link |
Now, it's been known for a long time, since the 60s,
link |
that if you look in the locus coeruleus of cats
link |
when they're awake, you find many neurons
link |
that have respiratory modulation.
link |
No one paid much attention to them.
link |
Not why bother paying attention,
link |
but why would the brain bother to have these inputs?
link |
So what Kevin did with Lindsey Schwartz
link |
and Lee Shun Low's lab is they killed a blade
link |
at those cells going to locus coeruleus from pre-Butzinger.
link |
And the animals became calmer.
link |
And their EEG levels changed in ways
link |
that are indicative that they became calmer.
link |
And as I recall, they didn't just become calmer,
link |
but they weren't really capable of high arousal states.
link |
They were kind of flat.
link |
I don't think we really pursued that in the paper.
link |
And so we'd have to ask Johnny Huguenard about that.
link |
He's on the other side of my lap, so we'll ask him.
link |
that beautifully illustrates
link |
how there is a bi-directional control, right,
link |
of emotion. Well, that's ascending.
link |
Well, no, the two stories of the locked-in syndrome
link |
plus the Yakl paper shows that emotional states
link |
influence breathing,
link |
and breathing influences emotional states.
link |
But you mentioned inspiration,
link |
which I always call inhalation, but people will follow.
link |
No, no, it's fine. Those are interchangeable.
link |
People can follow that.
link |
There's some interesting papers from Noam Sobel's group
link |
and from a number of other groups that as we inhale,
link |
or right after we inhale,
link |
the brain is actually more alert and capable
link |
of storing information than during exhales,
link |
which I find incredible, but it also makes sense.
link |
I'm able to see things far better when my eyes are open
link |
than when my eyelids are closed for that matter.
link |
Maybe, I don't doubt, I mean, Noam's work is great.
link |
Let me backtrack a bit because I want people to understand
link |
that when we're talking about breathing affecting
link |
emotional cognitive state,
link |
it's not simply coming from pre-Butzinger.
link |
There are at least, well, there are several other sites,
link |
and let me sort of, I need to sort of go through that.
link |
So when you're breathing, normal breathing,
link |
you're inhaling and exhaling.
link |
This is creating signals coming from the nasal mucosa
link |
that is going back into the olfactory bulb.
link |
That's respiratory modulated.
link |
And the olfactory bulb has a profound influence
link |
and projections through many parts of the brain.
link |
So there's a signal arising from this rhythmic moving
link |
of air in and out of the nose that's going into the brain
link |
that has contained in it a respiratory modulation.
link |
So that signal is there.
link |
The brain doesn't have to be using it,
link |
but when it's discriminating over and whatnot,
link |
that's riding on a oscillation which is respiratory related.
link |
Another potential source is the vagus nerve.
link |
The vagus nerve is a major nerve
link |
which is containing afferents from all of the viscera.
link |
Afferents just being signals too.
link |
Signals from the viscera.
link |
It also has signals coming from the brain stem down
link |
which are called efferents,
link |
but it's getting major signals from the lung,
link |
from the gut, and this is going up into the brain stem.
link |
There are very powerful receptors in the lung
link |
that are responding to the lung volume, the lung stretch.
link |
So, baro receptors.
link |
Sorry, well, we have a number like that,
link |
like the piezo receptors of this year's Nobel Prize, yeah.
link |
Yeah, so they're responding to the expansion
link |
and relaxation in the lung.
link |
And so if you record from the vagus nerve,
link |
you'll see that there's a huge respiratory modulation
link |
due to the mechanical changes in the lung.
link |
Now, why that is of interest is that
link |
for some forms of refractory depression,
link |
electrostimulation of the vagus nerve
link |
can provide tremendous relief.
link |
Why this is the case still remains to be determined,
link |
but it's clear that signals in the vagus nerve,
link |
at least artificial signals in the vagus nerve,
link |
can have a positive effect on reducing depression.
link |
So it's not a leap to think that
link |
under normal circumstances,
link |
that that rhythm coming in from the vagus nerve
link |
is playing a role in normal processing.
link |
Okay, let me continue.
link |
Carbon dioxide and oxygen levels.
link |
Now, under normal circumstances,
link |
your oxygen levels are fine.
link |
And unless you go to altitude,
link |
they don't really change very much.
link |
But your CO2 levels can change quite a bit
link |
with even a relatively small change
link |
in your overall breathing.
link |
That's gonna change your pH level.
link |
I have a colleague, Alicia Morette,
link |
who is working with patients who are anxious,
link |
and many of them hyperventilate.
link |
And as a result of that hyperventilation,
link |
their carbon dioxide levels are low.
link |
And she has developed a therapeutic treatment
link |
where she trains these people to breathe slower
link |
and to restore their CO2 levels back to normal,
link |
and she gets relief from their anxiety.
link |
So CO2 levels, which are not gonna affect brain function
link |
on a breath-by-breath level,
link |
although it does fluctuate breath-by-breath,
link |
but sort of as a continuous background, can change.
link |
And if it's changed chronically,
link |
we know that highly elevated levels of CO2
link |
can produce panic attacks.
link |
And we don't know the degree to that gets exacerbated
link |
by people who get, who have a panic attack,
link |
the degree to which their ambient CO2 levels
link |
are affecting their degree of discomfort.
link |
What about people who are, tend to be too calm,
link |
meaning they're feeling sleepy,
link |
they're underbreathing as opposed to overbreathing.
link |
Is there any knowledge of what the status of CO2
link |
is in their system?
link |
I don't know, which doesn't mean there's no knowledge,
link |
but I'm unaware, unaware, but that's blissfully unaware.
link |
I have not looked at that literature, so I don't know.
link |
And I have a feeling, I mean, most people,
link |
or excuse me, most of the scientific literature
link |
around breathing in humans that I'm aware of
link |
relates to these stress states
link |
because they're a little bit easier to study in the lab,
link |
whereas people feeling understimulated
link |
or exhausted all the time,
link |
it's a complicated thing to measure.
link |
I mean, you can do it, but it's not as straightforward.
link |
Well, CO2 is easier to measure.
link |
But in terms of the sort of,
link |
the measures for feeling fatigue,
link |
they're somewhat indirect,
link |
whereas stress, we can get at pulse rates in HRV
link |
and things of that sort.
link |
So imagine that these devices that we're all wearing
link |
will soon be able to measure,
link |
well, now they can measure oxygen levels, oxygen saturation.
link |
But oxins will pretty much stay above 90%
link |
unless there's some pathology or you go to altitude.
link |
But CO2 levels vary quite a bit.
link |
And in fact, because they vary, your body is so sensitive,
link |
the control of breathing,
link |
like how much you breathe per minute,
link |
is determined in a very sensitive way by the CO2 level.
link |
So even a small change in your CO2
link |
will have a significant effect on your ventilation.
link |
So this is another thing that not only changes
link |
your ventilation, but affects your brain state.
link |
Now, another thing that could affect breathing,
link |
how breathing practice can affect your emotional state
link |
is simply the descending command.
link |
Because breathing practice involves volitional control
link |
of your breathing.
link |
And therefore, there's a signal that's originating
link |
somewhere in your motor cortex.
link |
That is not, of course, that's gonna go down
link |
But it's also gonna send off collaterals to other places.
link |
Those collaterals could obviously influence
link |
your emotional state.
link |
So we have quite a few different potential sources.
link |
None of them are exclusive.
link |
And there's an interesting paper which shows
link |
that if you block nasal breathing,
link |
you still see breathing-related oscillations in the brain.
link |
And this is where I think the mechanism is occurring,
link |
is that these breathing-related oscillations in the brain,
link |
they are playing a role in signal processing.
link |
And maybe, should I talk a little bit about the role
link |
that oscillations may be playing in signal processing?
link |
Definitely, but before you do,
link |
I just want to ask you a intermediate question.
link |
We've talked a lot about inhalation,
link |
inspiration, and exhalation.
link |
What about breath holds?
link |
You know, in apnea, for instance,
link |
people are holding their breath,
link |
whether or not it's conscious or unconscious,
link |
they're holding their breath.
link |
What's known about breath holds
link |
in terms of how it might interact with brain state
link |
And I'm particularly interested in how breath holds
link |
with lungs empty versus breath holds with lungs full
link |
might differ in terms of their impact on the brain.
link |
I'm not aware of any studies on this,
link |
looking at a mechanistic level,
link |
but I find it really interesting.
link |
And even if there are no studies,
link |
I'd love it if you'd care to speculate.
link |
Well, one of the breath practices that intrigued me
link |
is where you basically hyperventilate for a minute
link |
and then hold your breath for as long as you can.
link |
Tummo style, Wim Hof style,
link |
or we call it in the laboratory
link |
because frankly, before Tummo and before Wim,
link |
it was referred to as cyclic hyperventilation.
link |
So it was basically, right, followed by a breath hold.
link |
And that breath hold could be done with lungs full
link |
So I had a long talk with some colleagues
link |
about what they might think the underlying mechanisms are,
link |
particularly for the breath hold.
link |
And I certainly envision that there's a component
link |
with respect to the presence or absence of that rhythmicity
link |
in your cortex which is having effect.
link |
But the other thing with the hyperventilation,
link |
hypoventilation, or the apnea,
link |
is your CO2 levels are going from low to high.
link |
Anytime you're holding your breath.
link |
Anytime you're holding your breath, okay.
link |
And those are gonna have a profound influence.
link |
Now, I have to talk about episodic hypoxia.
link |
Of course, there's a lot of work going on,
link |
particularly with Gordon Mitchell
link |
at the University of Florida
link |
is doing some extraordinary work on episodic hypoxia.
link |
So in the 80s, David Millhorn
link |
did some really intriguing work.
link |
If I ask you to hold your breath, excuse me,
link |
if I gave you a low oxygen mixture for a couple of minutes,
link |
your breathing level would go up
link |
because you wanna have more oxygen.
link |
You're starving for air, yeah.
link |
No, you're starving for oxygen, okay.
link |
And for a couple of minutes, you'd go up,
link |
you'd reach some steady state level.
link |
Not so hypoxic that you can't reach an equilibrium.
link |
And then I give you room there again,
link |
your ventilation quickly relaxes back down to normal.
link |
If on the other hand, I gave you three minutes of hypoxia,
link |
five minutes of normoxia,
link |
three minutes of hypoxia, five minutes of normoxia,
link |
three minutes of hypoxia, five minutes of normoxia.
link |
Normoxia being normal.
link |
Normal, normal air.
link |
Your ventilation goes up, down, up, down, up, down.
link |
After the last episode, your breathing comes down
link |
and doesn't continue to come down but rises again
link |
and stays up for hours, okay.
link |
This is well validated now.
link |
This was originally done in animals
link |
but in humans all the time.
link |
It seems to have profound benefit
link |
on motor function and cognitive function.
link |
In what direction?
link |
Positive, positive.
link |
I've often toyed with the idea of getting a 5%,
link |
an 8% oxygen, don't do this listeners,
link |
getting an 8% oxygen tank by my desk when I'm writing a grant
link |
and doing like in Blue Velvet
link |
and going through the episodic hypoxia
link |
to improve my cognitive function
link |
because certainly I could use improvement
link |
when I'm writing grants.
link |
But you could do this without the low oxygen.
link |
I mean, you could do this through breath work presumably.
link |
It's hard to lower your oxygen enough, okay.
link |
We're going in the experimental studies,
link |
they typically use 8% oxygen.
link |
It's hard to hold your breath long enough.
link |
And there is another difference here
link |
that is what's happening to your CO2 levels.
link |
When you hold your breath,
link |
your oxygen levels are dropping,
link |
your CO2 levels are going up.
link |
When you're doing episodic hypoxia,
link |
your CO2 levels are gonna stay pretty normal
link |
because you're still breathing,
link |
it's just the oxygen levels are gone.
link |
So unlike normal conditions which you described before
link |
where oxygen is relatively constant
link |
and CO2 is fluctuating depending on emotional state
link |
and activity and things of that sort,
link |
in episodic hypoxia, CO2 is relatively constant
link |
but you're varying the oxygen level
link |
coming into the system quite a bit.
link |
I would say it's relatively,
link |
I would say CO2 is relatively constant
link |
but it's not going to go in a direction
link |
which is gonna be significantly far from normal.
link |
Whereas when you're holding your breath,
link |
you're gonna become both hypoxic
link |
and hypo-capnic at the same time.
link |
We should explain to people
link |
what hypoxic and hypo-capnic are
link |
because we haven't done that.
link |
Hypoxic is just a technical term for low levels of oxygen.
link |
Or you could say hypoxic, low, hyper is high.
link |
So hyperoxia or hypo-capnia, low CO2
link |
or hyper-capnia, highest levels of CO2.
link |
So when you're in episodic hypoxia,
link |
if anything you're gonna become hypo-capnic
link |
And that could play an influence on this.
link |
One example that I remember
link |
and Gordon will have to forgive me
link |
if I'm misquoting this,
link |
is they had a patient who had a stroke
link |
and had weakness in ankle flexion.
link |
That is, excuse me, ankle extension to extend the ankle.
link |
And so they had the patient in a seat
link |
where they can measure ankle extension.
link |
And then they measured it.
link |
And then they exposed the patient to episodic hypoxia.
link |
And they measured again,
link |
the strength of the ankle extension went way up.
link |
And so Gordon is looking at this.
link |
They're looking at this now for spinal cord rehab.
link |
And I imagine for all sorts of neuromuscular performance,
link |
it could be beneficial.
link |
Gordon is looking into athletic performance.
link |
We have a project which we haven't been able
link |
to push to the next level to do golf.
link |
Because you love golf.
link |
Well, it's because it's motor performance, coordination.
link |
So it's not simply running as fast as you can.
link |
It's coordination, it's concentration.
link |
It's a whole variety of things.
link |
And so the idea would be to get a group of golfers
link |
and give them their placebo controls.
link |
They don't know whether they're breathing a gas mixture,
link |
which is just normal air or hypoxic gas mixture,
link |
although they may be able to figure it out
link |
based on their response.
link |
Do it under controlled circumstances,
link |
then do it into a net.
link |
Measure their length of their drives,
link |
their dispersion and whatnot, and see what happens.
link |
Look, if we could find that this works for golfers,
link |
forget about cognitive function.
link |
We could sell this for unbelievable amounts of money.
link |
That sounds like a terrible idea.
link |
By the way, I'm not serious about selling it.
link |
I know you're joking.
link |
Maybe people should know that you are joking by that.
link |
No, I think that anything that can improve cognitive
link |
and neuromuscular performance is going to be of interest
link |
for a wide range of both pathologic states
link |
like injury, TBI, et cetera.
link |
I mean, one of the most frequent questions I get
link |
is about recovery from concussion or traumatic brain injury.
link |
A lot of people think sports, they think football,
link |
they think rugby, they think hockey,
link |
but if you look at the statistics on traumatic brain injury,
link |
most of it is construction workers,
link |
car crashes, bicycle accidents.
link |
I mean, the sports part of it is a tiny, tiny,
link |
minuscule fraction of the total amount
link |
of traumatic brain injury out there.
link |
I think these protocols tested in the context of golf
link |
would be very interesting
link |
because of the constraints of the measures
link |
as you mentioned, and it could be exported
link |
to a number of things.
link |
I want to just try and imagine whether or not
link |
there is any kind of breathing patterned or breath work,
link |
just to be direct about it,
link |
that even partially mimics what you described
link |
in terms of episodic hypoxia.
link |
I've done a lot of Tummo, Wim Hof,
link |
cyclic hyperventilation type breathing before.
link |
My lab studies this in humans,
link |
and what we find is that
link |
if people do cyclic hyperventilation,
link |
so for about a minute, then exhale, hold their breath
link |
for 15 to 60 seconds, depending on what they can do,
link |
and just keep repeating that for about five minutes,
link |
it seems to me that it at least partially mimics
link |
the state that you're talking about.
link |
Because afterwards, people report heightened levels
link |
of alertness, lower levels of kind of triggering
link |
due to stressful events.
link |
They feel comfortable at a higher level
link |
of autonomic arousal, cognitive focus,
link |
a number of improvements that are pretty impressive.
link |
That any practitioner of Wim Hof or Tummo
link |
will be familiar with.
link |
Is that pattern of breathing even,
link |
can we say that it maps to what you're describing
link |
in some general sense?
link |
Well, the expert in this would be Gordon Mitchell.
link |
I would say it moves in that direction,
link |
but it's not as extreme,
link |
because I don't think you can get down
link |
to the levels of hypoxia that they do clinically.
link |
I know that our pals at our breath collective
link |
actually just bought a machine,
link |
because you buy a machine that does this,
link |
and they bought it and they're going to do
link |
their own self-testing to see whether or not
link |
this has any effect on anything that they can measure.
link |
Of course, you have to be concerned
link |
about self-experimentation,
link |
but I applaud their curiosity in going after it.
link |
Hyperbaric chambers.
link |
I hear a lot nowadays about hyperbaric chambers.
link |
People are buying them and using them,
link |
and what are your thoughts on hyperbaric chambers
link |
as it relates to any of the-
link |
Hyperbaric chambers.
link |
Okay, so you're not talking about altitude.
link |
I don't really have much to say.
link |
I mean, your oxygen levels will probably go up a little bit,
link |
and that could have a beneficial effect,
link |
but that's way outside my area of confidence.
link |
I think 2022, I think is going to be the year
link |
of two things I keep hearing a lot about,
link |
which is the deliberate use of high salt intake
link |
for performance, increasing blood volume, et cetera,
link |
and hyperbaric chambers seem to be catching on
link |
much in the same way that ice baths were
link |
and saunas seem to be right now.
link |
But anyway, a prediction we can return to at some point.
link |
I want to ask you about some of the studies
link |
that I've seen out there exploring
link |
how deliberately restricting one's breathing
link |
to nasal breathing can do things like improve memory.
link |
There's a couple of papers in Journal of Neuroscience,
link |
which is a respectable journal in our field,
link |
one looking at olfactory memory.
link |
So that kind of made sense because you can smell things
link |
better through your nose than your mouth,
link |
unless you're some sort of elk or something
link |
where they can, presumably they have some sense of smell
link |
in their mouth as well,
link |
but humans generally smell with their nose.
link |
That wasn't terribly surprising,
link |
but there was a companion study that showed
link |
that the hippocampus, an area involved in encoding memories
link |
in one form or another, was more active, if you will,
link |
and memory and recall was better
link |
when people learned information while nasal breathing
link |
as opposed to mouth breathing.
link |
Does that make sense from any mechanistic perspective?
link |
Well, given that there's a major pathway
link |
going from the olfactory system into the brain
link |
and not one from any receptors in the mouth,
link |
the degree of respiratory modulation
link |
you're gonna see throughout the forebrain
link |
is gonna be less with mouth breathing than nose breathing.
link |
So it's certainly plausible.
link |
I think there are a lot of experiments
link |
that need to be done to distinguish
link |
between the two, that is the nasal component
link |
and the non-nasal component
link |
of these breathing-related signals.
link |
There's a tendency sometimes when you have a strong effect
link |
to be exclusive, and I think what's going on here
link |
is that there are many inputs that can have an effect.
link |
Now, whether they're parceled,
link |
that some affect this part of behavior
link |
and some affect that part of behavior
link |
remains to be investigated.
link |
There's certainly a strong olfactory component.
link |
My interest is trying to follow the central component
link |
because we know that there's a strong central component.
link |
In fact, there's a strong central projection
link |
to the olfactory bulb.
link |
So regardless of whether or not
link |
there's any effluent in and out of the nose,
link |
there's a respiratory input into the olfactory bulb,
link |
which combines with the respiratory modulated signals
link |
coming from the sensory receptors.
link |
And as long as we are poking around, forgive the pun,
link |
the nose, what about one nostril versus the other nostril?
link |
I know it sounds a little crazy to imagine,
link |
but there have been theories in yogic traditions
link |
and others that breathing through one nostril
link |
somehow activates certain brain centers,
link |
maybe hemispherically one side of the brain versus the other,
link |
or that right nostril and left nostril breathing
link |
might differ in terms of the levels of alertness
link |
or calmness they produce.
link |
I'm not aware of any mechanistic data on that,
link |
but if there's anything worthwhile
link |
about right nostril versus left nostril breathing
link |
that you're aware of, I'd love to know.
link |
Well, it's certainly plausible.
link |
I don't know of any data demonstrating it
link |
except the anecdotal reports.
link |
As you know, the brain is highly lateralized
link |
and we have speech on one side
link |
and a dominant hand is on one side.
link |
And so the notion that if you have this huge signal
link |
coming from the olfactory system
link |
and to some degree it's lateralized,
link |
it's not perfectly symmetrical,
link |
that is one side is not going evenly to both sides,
link |
then you can imagine that once the signal gets distributed
link |
in a way that's not uniform,
link |
that the effectiveness or the response
link |
is gonna be particular to the cortex
link |
in which either the signal still remains
link |
or the signal is removed from.
link |
What are some of the other features of our brain and body,
link |
be it blinking or eye movements
link |
or ability to encode sounds
link |
or any features of the way that we function
link |
and move and perceive things
link |
that are coordinated with breathing in some interesting way?
link |
Thank you for that question.
link |
Almost everything.
link |
So we have, for example, on the autonomic side,
link |
we have respiratory sinus arrhythmia,
link |
that is during expiration, the heart slows down.
link |
Your pupils oscillate with the respiratory cycle.
link |
I don't know what the functional basis for that is,
link |
but they do oscillate with the respiratory cycle.
link |
When we inhale, our pupils constrict, presumably,
link |
because there's an increase in heart rate
link |
and sympathetic tone, I would think of constriction.
link |
And I'm guessing as you relax,
link |
the people will get, and you exhale,
link |
the people wouldn't go. I think you're right,
link |
but I always get the valence of that.
link |
Well, it's counterintuitive
link |
because people wouldn't think that when the pupils get,
link |
I mean, it depends.
link |
I mean, you can get very alert and aroused
link |
and that for stress or for good reasons,
link |
and the pupils get wider, but your visual field narrows,
link |
and then the opposite is true.
link |
Anyway, I guess the idea is that the pupils
link |
are changing size and therefore the aperture
link |
of your visual window is changing
link |
in coordination with breathing.
link |
Your fear response changes with the respiratory cycle.
link |
Tell us more about that.
link |
Well, there's a paper by Zolano,
link |
which I think showed rather clearly
link |
that if you show individuals fearful faces,
link |
that their measured response of fearfulness
link |
changes between inspiration and expiration.
link |
You know, I don't know why, but it does.
link |
Your reaction time changes.
link |
So you talk about blinking,
link |
the reaction time changes between inspiration and expiration.
link |
If I asked you to punch something,
link |
that time will change between inspiration and expiration.
link |
In fact, I don't know the degree
link |
to which martial artists exploit that.
link |
You know, you watch the breathing pattern
link |
and your opponent will actually move slower
link |
during one cycle compared to the other.
link |
Meaning as they're, in which direction?
link |
If they're exhaling, they can punch faster?
link |
I have to say, I don't keep a table
link |
of which direction things move in
link |
because I'm out of the martial arts field now.
link |
My vague understanding is that exhales on strikes
link |
is the more typical way to do that.
link |
And so as people strike, they exhale.
link |
No, as you exhale.
link |
But there are other components to striking
link |
because you want to stiffen your rib cage,
link |
you want to make a valsalva maneuver.
link |
So that's, you know, both an inspiration
link |
and an expiration, it's at the same time.
link |
So I don't know enough about when you say during expiration,
link |
I would assume that when you make your strike,
link |
you actually sort of want to stiffen here,
link |
which is a valsalva-like maneuver.
link |
And oftentimes they'll clench their fist at the last moment.
link |
Anyway, there's a whole set of motor things there
link |
that we can talk to some fighters.
link |
We know people who know fighters, so we can ask them.
link |
Interesting, what are some other things
link |
that are modulated by breathing?
link |
You know, I think anything anyone looks at
link |
seems to have a breathing component
link |
because it's all over your brain.
link |
And it's hard to imagine it not being effective.
link |
Now, whether it's incidental
link |
or just background and doesn't really have
link |
any behavioral advantage is possible.
link |
In other cases, it might have a behavioral advantage.
link |
I mean, the big, this eye-opening thing for me
link |
probably a decade ago was digging into literature
link |
and seeing how much of cortical activity
link |
and subcortical activity
link |
had a respiratory modulated component to it.
link |
And I think a lot of my colleagues who are studying cortex
link |
are oblivious to this.
link |
And they find, I heard a talk the other day
link |
of a person who'll go unnamed,
link |
who find a lot of things correlated
link |
with a particular movement.
link |
And I think it all, when I looked, I said,
link |
gee, that's a list of things that are respiratory modulated.
link |
And rather than it being correlated
link |
to the movement they were looking at,
link |
I think the movement they were looking at
link |
was modulated by breathing, as was everything else.
link |
So there wasn't that the movement itself
link |
was driving that correlation,
link |
it was that they were all correlated to something else,
link |
which is the breathing movement.
link |
And whether or not that is a behaviorally relevant
link |
or behaviorally something you can exploit, I don't know.
link |
I suspect you're right, that breathing is, if not the,
link |
foundational driver of many, if not all of these things,
link |
that it's at least one of the foundational drivers.
link |
It's in the background, it's in the brain,
link |
and oscillations play an important part in brain function.
link |
And they vary in frequency from maybe a hundred hertz
link |
down to, well, we can get to circadian
link |
and sort of monthly cycles.
link |
But breathing occupies a rather unusual place in all that
link |
because, so let me talk about what people think
link |
the oscillations are doing, particularly the faster ones.
link |
They're important in coordinating signals across neurons.
link |
Just like in a computer, a computer steps.
link |
So a computer knows when information is coming
link |
from another part of a computer
link |
that it was originated at a particular time.
link |
And so that discrete step-by-step thing
link |
is important in computer control.
link |
Now the brain is not a digital device,
link |
it's an analog device.
link |
But when I have a signal that coming in my ear and my eye,
link |
which is Andrew Huberman speaking,
link |
and I'm looking at his face, I see that as a whole,
link |
but the signal is coming into different parts of my brain.
link |
How do I unify that?
link |
Well, my neurons are very sensitive to changes
link |
in signals arriving by fractions of a millisecond.
link |
So how do I assure that those signals coming in
link |
represent the same signal?
link |
Well, if I have throughout my brain an oscillation
link |
and the signals ride on that oscillation,
link |
let's say the peak of the oscillation,
link |
I can then have a much better handle on the road of timing
link |
and say those two signals came in at the same time,
link |
they may relate to the same object,
link |
and aha, I see you as one unified thing spouting,
link |
you know, talking.
link |
And so these oscillations come in many different frequency
link |
ranges and are important in memory formation
link |
and all sorts of things.
link |
I don't think people pay much attention to breathing
link |
because it's relatively slow to this, the range when you
link |
think about milliseconds.
link |
But we have important things that
link |
are thought to be important in cognitive function, which
link |
are a few cycles per second to 20, 30, 40, 50 cycles per second.
link |
Breathing in humans is maybe 0.2 cycles per second,
link |
every five seconds, although in rodents,
link |
they're up to four per second, which is pretty fast.
link |
But breathing has one thing which is special.
link |
That is, you can readily change it.
link |
So the degree to which the brain is
link |
using that slow signal for anything,
link |
if that becomes part of its normal signal processing,
link |
you now change it, that signal processing has to change.
link |
And as that signal processing changes,
link |
acutely there's a change.
link |
So, you know, you asked about breath practice,
link |
how long do you have to do it?
link |
Well, a single breath will change your state.
link |
You know, you're nervous, you take a deep breath,
link |
and it seems to help relax.
link |
Call it what you will.
link |
Call it what you will.
link |
Now, it doesn't have a permanent change,
link |
but, you know, when I'm getting up to bat
link |
or getting up to the first tea or getting to give a big talk
link |
or coming to do a podcast, get a little bit anxious,
link |
a deep breath or a few deep breaths
link |
are tremendously effective in calming one down.
link |
And so you can get a transient disruption.
link |
But on the other hand, let's take something
link |
I think you can envision depression
link |
as activity sort of going around in a circuit.
link |
And because it's continuous in the nervous system
link |
as signals keep repeating, they tend to get stronger.
link |
And they can get so strong, you can't break them.
link |
So you can imagine depression being something
link |
going on and on and on, and you can't break it.
link |
And so we have trouble when we get
link |
to certain levels of depression.
link |
I mean, all of us get depressed at some point.
link |
But if it's not continuous, it's not long-lasting,
link |
we're able to break it.
link |
But if it's long-lasting and very deep, we can't break it.
link |
So the question is, how do we break it?
link |
Well, there are extreme measures to break it.
link |
We could do electroconvulsive shock.
link |
We shock the whole brain.
link |
That's disrupting activity in the whole brain.
link |
And when the circuit starts to get back together again,
link |
it's been disruptive.
link |
And we know that the brain, when signals
link |
get disrupted a little bit, we can weaken the connections.
link |
And weakening the connections, if it's
link |
then in the circuit involved in depression,
link |
we may get some relief.
link |
And electroconvulsive shock does work
link |
for relieving many kinds of depression.
link |
That's pretty heroic.
link |
Focal deep brain stimulation does the same thing,
link |
but more localized, or transcranial stimulation.
link |
You're disrupting a network.
link |
And while it's getting back together,
link |
it may weaken some of the connections.
link |
If breathing is playing some role in this circuit,
link |
and now instead of doing like a one-second shock,
link |
I do 30 minutes of disruption by doing slow breathing
link |
or other breathing practice, those circuits
link |
begin to break down a little bit.
link |
And I get some relief.
link |
And if I continue to do it before the circuit can then
link |
build back up again, I gradually can wear that circuit down.
link |
I sort of liken this.
link |
I tell people it's like walking around on a dirt path.
link |
You build a rut, the rut gets so deep you can't get out of it.
link |
And what breathing is doing is sort of filling in the rut
link |
bit by bit to the point that you can climb out of that rut.
link |
And that is because breathing, the breathing signal
link |
is playing some role in the way the circuit works.
link |
And then when you disrupt it, the circuit
link |
gets a little thrown off kilter.
link |
And as you know, when circuits get thrown off,
link |
the nervous system tries to adjust in some way or another.
link |
And it turns out, at least for breathing,
link |
for some evolutionary reason or just by happenstance,
link |
it seems to improve our emotional function
link |
or our cognitive function.
link |
And we're very fortunate that that's the case.
link |
It's a terrific segue into what I want to ask you next.
link |
And this is part of a set of questions
link |
I want to make sure we touch on before we wrap up,
link |
which is what do you do with all this knowledge
link |
in terms of a breathing practice?
link |
You mentioned that one breath can shift your brain state
link |
and that itself can be powerful.
link |
I think that's absolutely true.
link |
You've also talked about 30 minute breath work practices,
link |
which is 30 minutes of breath work
link |
is a pretty serious commitment, I think, but it's doable.
link |
Certainly a zero cost except for the time in most cases.
link |
What do you see out there in the landscape of breath work
link |
that's being done that you like and why do you like it?
link |
What do you think or what would you like to see more of
link |
in terms of exploration of breath work and what do you do?
link |
Well, I'm a relatively new convert to breath work.
link |
Through my own investigation of it,
link |
I became convinced that it's real.
link |
And I'm basically a beginner in terms of my own practice.
link |
And I like to keep things simple.
link |
And I think I've discussed this before.
link |
I liken it to someone who's a couch potato
link |
who's told they got to begin to have a
link |
to exercise, you don't go out and run a marathon.
link |
So, couch potato, you say,
link |
okay, get up and walk for five minutes and 10 minutes.
link |
And then, okay, now you're walking for a longer period,
link |
And then you reach a point and say,
link |
well, gee, I'm interested in this sport.
link |
And there may be particular kinds of practices
link |
that you can use that could be helpful
link |
in optimizing performance at that sport.
link |
I'm not there yet.
link |
I find I get tremendous benefit by relatively short periods
link |
between five and maybe 20 minutes of doing box breathing.
link |
It's very simple to do.
link |
I have a simple app which helps me keep the timing.
link |
Do you recall which app it is?
link |
Is it the Apnea Trainer?
link |
Well, I was using Calm for a long time,
link |
but I let my subscription relapse
link |
and I have another one whose name I don't remember.
link |
But so it's very simple and it works for me.
link |
Now trying this Tummo because I'm just curious
link |
and exploring it because it may be acting
link |
through a different way.
link |
And I wanna see if I respond differently.
link |
So I don't have a particular point of view now.
link |
I have friends and colleagues who are into particular styles
link |
like Wim Hof and I think what he's doing is great
link |
in getting people who are interested.
link |
I think the notion is that I would like to see
link |
more people exploring this and to some degree,
link |
as you point out, 30 minutes a day,
link |
some of the breath patterns that some of these styles
link |
like Wim Hof are a little intimidating to newbies.
link |
And so I would like to see something very simple
link |
that what I tell my friends is look,
link |
just try it five or 10 minutes, see if you feel better,
link |
do it for a few days.
link |
If you don't like it, stop it, it doesn't cost anything.
link |
And invariably they find that it's helpful.
link |
I will often interrupt my day to take five or 10 minutes.
link |
Like if I find that I'm lagging,
link |
I think there's some pretty good data
link |
that your performance after lunch declines.
link |
And so very often what I'll do after lunch,
link |
which I didn't do today, is take five or 10 minutes
link |
and just sort of breath practice.
link |
Lately, what does that breath practice look like?
link |
It's just box breathing for five or 10 minutes.
link |
And the duration of your inhales and holds and exhales
link |
and holds is set by the app, is that right?
link |
Well, I do five seconds.
link |
So five seconds, inhale, five second hold,
link |
five second exhale, five second hold.
link |
And sometimes I'll do doubles.
link |
I'll do 10 seconds just because I get bored.
link |
I feel like doing it.
link |
And it's very helpful.
link |
Now that's not the only thing I do with respect
link |
to trying to maintain my sanity and my health.
link |
No, I can imagine there'll be a number of things.
link |
Although you seem, because you seem very sane
link |
and very healthy, I in fact know that you are.
link |
Both of those things.
link |
Well, you suspect that.
link |
I suspect, but there's data.
link |
A while back, we had a conversation, a casual conversation,
link |
but you said something that really stuck in my mind,
link |
which is that it might be that the specific pattern
link |
of breath work that one does is not as important
link |
as experiencing transitions between states
link |
based on deliberate breath work or something to that extent,
link |
which I interpreted to mean that if I were to do
link |
box breathing with five second in, five second hold,
link |
five second exhale, five second hold for a couple of days,
link |
or maybe even a couple of minutes,
link |
and then switch to 10 seconds, or then switch to Tummo,
link |
that there's something powerful perhaps in the transitions
link |
and realizing the relationship between different patterns
link |
of breathing and those transitions.
link |
Much in the same way that you can get into one of these cars
link |
at an amusement park that just goes at a constant rate
link |
Very different than learning how to shift gears.
link |
I used to drive a manual, I still can,
link |
so I'm thinking about a manual transmission,
link |
but even with an automatic transmission,
link |
you start to get a sense of how the vehicle behaves
link |
under different conditions.
link |
And I thought that was a beautiful seed
link |
for a potential breath work practice that,
link |
at least to my awareness, nobody has really formalized,
link |
which is that you introduce some variability
link |
within the practice that's somewhat random
link |
in order to be able to sense the relationship
link |
between different speeds and depths of inhales,
link |
exhales, and holds, and so forth.
link |
And essentially, it's like driving around the track,
link |
but with obstacles at different rates,
link |
and braking, and restarting, and things of that sort.
link |
That's how you learn how to drive.
link |
What do you think about that?
link |
And if you like it enough,
link |
can we call it the Feldman protocol?
link |
You know, I was asked in this BBC interview once,
link |
why didn't I name it the Feldman complex
link |
instead of the pre-busting complex?
link |
I said I already have a Feldman complex.
link |
Well, it sounds like a psychiatric disorder,
link |
but I think the primary effect
link |
is this disruptive effect, which I described.
link |
And, but the particular responses may clearly vary
link |
depending on what that disruption is.
link |
I don't know of any particular data
link |
which are some well-controlled experiments,
link |
which can actually work through
link |
the different types of breathing patterns,
link |
or simply with a box pattern, just varying the durations.
link |
I mean, Prayama is sort of similar,
link |
but the amount of time you spend
link |
going around the box is different.
link |
So I don't really have much to say about this.
link |
I mean, this is why we need
link |
better controlled experiments in humans.
link |
And I think this is where being able to study it in rodents,
link |
where you can have a wide range of
link |
perturbations while you're doing more invasive studies
link |
to really get down as to which regions are affected,
link |
how is the signal processing disrupted,
link |
which is still a hypothesis, but how it's disrupted.
link |
It could tell us a lot about, you know,
link |
maybe there's a resonant point
link |
at which there's an optimal effect
link |
when you take a particular breathing practice.
link |
And then when we talked about, you know,
link |
the fact that different breathing practices
link |
could be affecting the outcome through different pathways.
link |
You know, you have the olfactory pathway,
link |
you have a central pathway, you have a vagal pathway,
link |
you have a descending pathway,
link |
how different practices may
link |
change the summation of those things,
link |
because I think all those things are probably involved.
link |
And we're just beginning to scratch the surface.
link |
And I just hope that we can get serious neuroscientists
link |
and psychologists to do the right experiments
link |
to get at this, because I think there's a lot of value
link |
to human health here.
link |
I do too, and it's one of the reasons my lab
link |
has shifted to these sorts of things in humans.
link |
I'm delighted that you're continuing to do
link |
the hardcore mechanistic work in mice
link |
and probably do work in humans as well,
link |
if you're not already.
link |
And there are other groups, Epple Lab at UCSF
link |
and a number of, I'm starting to see some papers out there
link |
about respiration in humans a little bit,
link |
some more brain imaging.
link |
I can't help but ask about a somewhat unrelated topic,
link |
but it is important in light of this conversation
link |
because you're here.
link |
And one of the things that I really enjoy
link |
about conversations with you as it relates to health
link |
and neuroscience and so forth is that
link |
you're one of the few colleagues I have
link |
who openly admits to exploring supplementation.
link |
I'm a long time supplement fan.
link |
I think there's power in compounds,
link |
both prescription, non-prescription, natural, synthesized.
link |
I don't use these haphazardly,
link |
but I think there's certainly power in them.
link |
And one of the places where you and I converge
link |
in terms of our interest in the nervous system
link |
and supplementation is vis-a-vis magnesium.
link |
Now I've talked endlessly on the podcast and elsewhere
link |
about magnesium for sake of sleep
link |
and improving transitions to sleep and so forth.
link |
But you have a somewhat different interest in magnesium
link |
as it relates to cognitive function
link |
and durability of cognitive function.
link |
Would you mind just sharing with us a little bit
link |
about what that interest is, where it stems from,
link |
and because it's the Human Men Lab podcast
link |
and we often talk about supplementation,
link |
what you do with that information?
link |
So I need to disclose that I am a scientific advisor
link |
to a company called Neurocentria,
link |
which my graduate student called Song Liu was CEO.
link |
So that said, I can give you some background.
link |
Guo Song, although when he was in my lab,
link |
worked on breathing,
link |
had a deep interest in learning and memory.
link |
And when he left my lab, he went to work for it
link |
with a renowned learning and memory guy
link |
at Stanford, Dick Chen.
link |
And when he finished there,
link |
he was hired by Susumu Tonogawa at MIT.
link |
Who also knows a thing or two about memory.
link |
I'm teasing, Susumu has a Nobel for his work on
link |
immunoglobulins, but then is a world-class memory researcher.
link |
And Guo Song had very curious, very bright guy,
link |
and he was interested in how signals between neurons
link |
get strengthened, which is called
link |
long-term potentiation or LTP.
link |
And one of the questions that arose was,
link |
if I have inputs to a neuron and I get LTP,
link |
is the LTP bigger if the signal is bigger
link |
or the noise is less?
link |
So we can imagine that when we're listening to something,
link |
if it's louder, we can hear it better.
link |
Or if there's less noise, we can hear it better.
link |
And he wanted to investigate this.
link |
So he did this in tissue culture of hippocampal neurons.
link |
And what he found was that if he lowered
link |
the background activity in all of the neurons,
link |
that the LTP he elicited got stronger.
link |
And the way he did that was increasing
link |
the level of magnesium in the bathing solution.
link |
This gets into some esoteric electrophysiology,
link |
but basically there's a background level
link |
of noise in all neurons and that part of it is regulated
link |
by the degree of magnesium in the extracellular bath.
link |
And you mean electrical noise?
link |
Electrical noise, I'm sorry, electrical noise.
link |
And if you, in what's called the physiological range,
link |
which is between 0.8 and 1.2 millimolar,
link |
which, don't worry about the number.
link |
I can't believe I remember the millimolar
link |
of the magnesium in that.
link |
Well, I'm always frightened that I get,
link |
you know, I say micro or femto or something,
link |
I go off by several loads of magnitude.
link |
So in that physiological range,
link |
there's a big difference in the amount of noise
link |
in a neuron between 0.8 and 1.2 millimolar.
link |
So he played around with the magnesium
link |
and he found out that when the magnesium was elevated,
link |
there was more LTP.
link |
All right, that's an observation in a tissue culture.
link |
Right, and I should just mention that more LTP
link |
essentially translates to more neuroplasticity,
link |
more rewiring of connections in essence.
link |
So he tested this in mice
link |
and basically he offered them a,
link |
he had control mice, which got a normal diet
link |
and one that had more than the rich magnesium
link |
and the ones that lived enriched with magnesium
link |
had higher cognitive function, lived longer,
link |
everything you'd want in some magic pill.
link |
Those mice did that, excuse me, rats.
link |
The problem was that you couldn't imagine
link |
taking this into humans because most magnesium salts
link |
don't passively get from the gut
link |
into the bloodstream, into the brain.
link |
They pass via what's called a transporter.
link |
Transporter is something in a membrane
link |
that grabs a magnesium molecule or atom
link |
and pulls it into the other side.
link |
So if you imagine you have magnesium in your gut,
link |
you have transporters that pull the magnesium
link |
into the gut into the bloodstream.
link |
Well, if you had taken normal magnesium supplement
link |
that you can buy at the pharmacy,
link |
it doesn't cross the gut very easily
link |
and if you would take enough of it
link |
to get it in your bloodstream, you start getting diarrhea.
link |
So it's not a good way to go.
link |
Oh, it is a good way to go.
link |
Oh, I couldn't help myself.
link |
So he worked with this brilliant chemist, Fei Mao,
link |
and Fei looked at a whole range of magnesium compounds
link |
and he found the magnesium threonate
link |
was much more effective in crossing the gut blood barrier.
link |
Now, they didn't realize at the time,
link |
but threonate is a metabolite of vitamin C
link |
and there's lots of threonate in your body.
link |
So magnesium threonate would appear to be safe
link |
and maybe a part of the role
link |
or now they believe it's part of the role of the threonate
link |
is that it supercharges the transporter
link |
to get the magnesium in.
link |
And remember, you need a transporter at the gut,
link |
into the brain and into cells.
link |
So they gave magnesium threonate to mice who had...
link |
No, let me backtrack a bit.
link |
They did a study in humans.
link |
They hired a company to do a test.
link |
It was a hands-off test.
link |
It's one of these companies that gets hired
link |
by the big pharma to do their test for them.
link |
And they got patients who were diagnosed
link |
as mild cognitive decline.
link |
These are people who had cognitive disorder,
link |
which was age inappropriate.
link |
And the metric that they use for determining
link |
how far off they were is Spearman's G-factor,
link |
which is a generalized measure of intelligence
link |
that most psychologists accept.
link |
And the biological age of the subjects was,
link |
I think 51 and the cognitive age was 61
link |
based on the Spearman G-factor.
link |
I should say the Spearman G-factor
link |
starts at a particular level in the population
link |
at age 20 and declines about 1% a year.
link |
So sorry to say, we're not 20 year olds anymore.
link |
But when you get a number from that,
link |
you can put on the curve and see whether
link |
it's about your age or not.
link |
These people were about 10 years older
link |
according to that metric.
link |
And long story short, after three months,
link |
this is a placebo-controlled double-blind study.
link |
The people who were in the placebo arm
link |
improved two years, which is common for human studies
link |
because of the placebo effect.
link |
The people who got the compound
link |
improved eight years on average.
link |
And some improved more than eight years.
link |
They didn't do any further diagnosis
link |
as to what caused the monoclonal decline.
link |
But it was pretty, it was extraordinarily impressive.
link |
So it moved their cognition closer to their biological age.
link |
Do you recall what the dose is of magnesium 3-N-H?
link |
It's in the paper and it's basically
link |
what they have in the compound,
link |
which is sold commercially.
link |
So the compound, which is sold commercially,
link |
is handled by a nutraceutical compound
link |
or nutraceutical wholesaler who sells it to the retailers
link |
and they make whatever formulation they want.
link |
But it's a dosage which is,
link |
my understanding is, readily tolerable.
link |
I take half a dose.
link |
The reason I take half a dose
link |
is that I had my magnesium, blood magnesium measured
link |
and it was low normal for my age.
link |
I took half a dose, it became high normal.
link |
And I felt comfortable staying in the normal range.
link |
But, you know, a lot of people are taking the full dose
link |
I'm not looking to get smarter.
link |
I'm looking to decline more slowly.
link |
And it's hard for me to tell you
link |
whether or not it's effective or not.
link |
Well, you remembered the millimolar of the magnesium
link |
and the solution and on the high and low end.
link |
So I would say it's not a well-controlled study
link |
when it's an N of one, but it seems to be working.
link |
When I've recommended it to my friends,
link |
academics who are not by nature skeptical, if not cynical,
link |
and I insist that they try it,
link |
they usually don't report a major change
link |
in their cognitive function,
link |
although sometimes they do report,
link |
well, I feel a little bit more alert and my physical movements
link |
are better, but many of them report their sleep better.
link |
And that makes sense.
link |
I think there's good evidence that three and eight
link |
can accelerate the transition into sleep
link |
and maybe even access to deeper modes of sleep
link |
There are, for many people actually,
link |
a small percentage of people who take three and eight,
link |
including one of our podcast staff here,
link |
have stomach issues with it.
link |
They can't tolerate it.
link |
I would say just anecdotally,
link |
about 5% of people don't tolerate three and eight well.
link |
You stop taking it and then they're fine.
link |
It caused them diarrhea or something of that sort,
link |
but most people tolerate it well.
link |
And most people report that it vastly improves their sleep.
link |
And again, that's anecdotally.
link |
There are a few studies and they're more on the way,
link |
but that's very interesting because I,
link |
until you and I had the discussion about three and eight,
link |
I wasn't aware of the cognitive enhancing effects,
link |
but the story makes sense from a mechanistic perspective.
link |
And it brings you around to a bigger
link |
and more important statement,
link |
which is that I so appreciate your attention to mechanism.
link |
I guess this stems from your early training as a physicist
link |
and the desire to get numbers
link |
and to really parse things at a fine level.
link |
So we've covered a lot today.
link |
I know there's much more that we could cover.
link |
I'm going to insist on a part two at some point,
link |
but I really want to speak on behalf
link |
of a huge number of people and just thank you,
link |
not just for your time and energy and attention to detail
link |
and accuracy and clarity around this topic today,
link |
but also what I should have said at the beginning,
link |
which is that, you know,
link |
you really are a pioneer in this field
link |
of studying respiration and the mechanisms
link |
underlying respiration with modern tools
link |
for now for many decades, you know,
link |
and the field of neuroscience was one
link |
that was perfectly content to address issues
link |
like memory and vision and, you know,
link |
sensation, perception, et cetera,
link |
but the respiratory system was largely overlooked
link |
And you've just been steadily clipping away
link |
and clipping away and much because of the events
link |
related to COVID and a number of other things
link |
and this huge interest in breath work
link |
and brain states and wellness,
link |
the field of respiration and interest in respiration
link |
has just exploded.
link |
So I really want to extend a sincere thanks.
link |
It means a lot to me.
link |
And I know to the audience of this podcast
link |
that someone with your depth and rigor in this area
link |
is both a scientist and a practitioner
link |
and that you would share this with us.
link |
Well, I want to thank you.
link |
This is actually a great opportunity for me.
link |
I've been isolated in my silo for a long time
link |
and it's been a wonderful experience
link |
to communicate to people outside the silo
link |
who have an interest in this.
link |
And I think that there's a lot that remains to be done.
link |
And I enjoy speaking to people who have interest in this.
link |
I find the interest to be quite mind-boggling
link |
and it's quite wonderful that people are willing
link |
to listen to things that can be quite esoteric at times,
link |
but it gets down to deep things about who we are
link |
and how we are going to live our lives.
link |
So I appreciate the opportunity
link |
and I would be delighted to come back at any time.
link |
We will absolutely do it.
link |
Thanks again, Jack.
link |
Thank you for joining me for my conversation
link |
with Dr. Jack Feldman.
link |
I hope you found it as entertaining
link |
and as informative as I did.
link |
If you're learning from and or enjoying this podcast,
link |
please subscribe to us on YouTube.
link |
That's a terrific zero cost way to support us.
link |
In addition, please subscribe to the podcast
link |
on Spotify and Apple.
link |
And on Apple, you can leave us a review
link |
and you can leave us up to a five-star rating.
link |
Please also check out the sponsors mentioned
link |
at the beginning of the podcast.
link |
That's the best way to support this podcast.
link |
We also have a Patreon.
link |
It's patreon.com slash Andrew Huberman.
link |
And there you can support the Huberman Lab Podcast
link |
at any level that you like.
link |
In addition, if you're not already following us
link |
on Instagram and Twitter,
link |
I teach neuroscience on Instagram and Twitter.
link |
Some of that information covers information
link |
covered on the podcast.
link |
Some of that information is unique information,
link |
and that includes science and science-based tools
link |
that you can apply in everyday life.
link |
During today's podcast and on many previous podcast episodes
link |
we talk about supplements.
link |
While supplements aren't necessary for everybody,
link |
many people derive tremendous benefit from them.
link |
One of the key issues with supplements,
link |
if you're going to take them,
link |
is that they be of the utmost quality.
link |
For that reason, the Huberman Lab Podcast
link |
has partnered with Thorne, T-H-O-R-N-E.
link |
Thorne supplements are of the very highest quality,
link |
both with respect to the quality
link |
of the ingredients themselves
link |
and the precision of the amounts of the ingredients.
link |
Why do I say that?
link |
Well, many supplement companies out there
link |
list amounts of particular substances on the bottle.
link |
And when they've been tested,
link |
they do not match up to what's actually in those products.
link |
Thorne has the highest levels of stringency for quality
link |
and the particular amounts that are in each product.
link |
They partnered with the Mayo Clinic
link |
and all the major sports teams.
link |
So there's tremendous trust in Thorne products.
link |
That's why we partnered with them.
link |
If you're interested in seeing the supplements that I take,
link |
you can go to thorne.com slash the letter U slash Huberman.
link |
You can see the supplements that I take from Thorne.
link |
If you purchase any of those supplements there,
link |
you can get 20% off.
link |
And if you navigate further into the Thorne site
link |
to see the huge array of other products that they make,
link |
if you go in through thorne.com slash U slash Huberman,
link |
you'll also get 20% off any of the products
link |
that Thorne makes.
link |
I also want to just mention one more time,
link |
the program that I mentioned at the beginning
link |
of the episode, which is Our Breath Collective.
link |
The Our Breath Collective has an advisory board
link |
that includes people like Dr. Jack Feldman,
link |
where you can learn detailed breath work protocols.
link |
If you're interested in doing or teaching breath work,
link |
I highly recommend checking it out.
link |
You can find it at ourbreathcollective.com slash Huberman,
link |
and that will give you $10 off your first month.
link |
So I want to thank you once again for joining me
link |
for my conversation with Dr. Jack Feldman.
link |
And last, but certainly not least,
link |
thank you for your interest in science.
link |
I'll see you next time.