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

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.240 | and I'm a professor of neurobiology and ophthalmology

00:00:12.640 | at Stanford School of Medicine.

00:00:14.620 | Today, my guest is Dr. Jack Feldman.

00:00:17.220 | Dr. Jack Feldman is a distinguished professor of neurobiology

00:00:20.520 | at the University of California, Los Angeles.

00:00:23.280 | He is known for his pioneering work

00:00:25.360 | on the neuroscience of breathing.

00:00:27.800 | We are all familiar with breathing

00:00:29.400 | and how essential breathing is to life.

00:00:31.920 | We require oxygen, and it is only by breathing

00:00:34.460 | that we can bring oxygen to all the cells

00:00:36.760 | of our brain and body.

00:00:38.400 | However, as the work from Dr. Feldman and colleagues

00:00:41.220 | tells us, breathing is also fundamental

00:00:43.920 | to organ health and function

00:00:45.760 | at an enormous number of other levels.

00:00:48.160 | In fact, how we breathe, including how often we breathe,

00:00:51.680 | the depth of our breathing,

00:00:52.700 | and the ratio of inhales to exhales

00:00:56.260 | actually predicts how focused we are,

00:00:58.560 | how easily we get into sleep,

00:01:00.640 | how easily we can exit from sleep.

00:01:02.920 | Dr. Feldman gets credit for the discovery

00:01:05.160 | of the two major brain centers

00:01:06.760 | that control the different patterns of breathing.

00:01:09.320 | Today, you'll learn about those brain centers

00:01:11.080 | and the patterns of breathing they control

00:01:12.840 | and how those different patterns of breathing

00:01:14.760 | influence all aspects of your mental and physical life.

00:01:18.720 | What's especially wonderful about Dr. Feldman and his work

00:01:21.880 | is that it not only points to the critical role

00:01:24.320 | of respiration in disease, in health, and in daily life,

00:01:28.640 | but he's also a practitioner.

00:01:29.960 | He understands how to leverage particular aspects

00:01:32.640 | of the breathing process in order to bias the brain

00:01:36.120 | to be in particular states that can benefit us all.

00:01:39.320 | Whether or not you are a person

00:01:40.480 | who already practices breath work,

00:01:42.120 | or whether or not you're somebody

00:01:43.160 | who simply breathes to stay alive,

00:01:45.160 | by the end of today's discussion,

00:01:47.040 | you're going to understand a tremendous amount

00:01:49.400 | about how the breathing system works

00:01:51.360 | and how you can leverage that breathing system

00:01:53.600 | toward particular goals in your life.

00:01:55.640 | Dr. Feldman shares with us

00:01:57.000 | his own particular breathing protocols that he uses,

00:02:00.160 | and he suggests different avenues for exploring respiration

00:02:03.800 | in ways that can allow you, for instance,

00:02:05.720 | to be more focused for work,

00:02:07.360 | to disengage from work in high stress endeavors,

00:02:10.040 | to calm down quickly.

00:02:11.400 | And indeed, he explains not only how to do that,

00:02:13.780 | but all the underlying science in ways that will allow you

00:02:16.360 | to customize your own protocols for your needs.

00:02:19.600 | All the guests that we bring on the Huberman Lab Podcast

00:02:22.040 | are considered at the very top of their fields.

00:02:24.800 | Today's guest, Dr. Feldman,

00:02:26.760 | is not only at the top of his field, he founded the field.

00:02:30.360 | Prior to his coming into neuroscience

00:02:32.060 | from the field of physics,

00:02:33.400 | there really wasn't much information

00:02:34.880 | about how the brain controls breathing.

00:02:36.480 | There was a little bit of information,

00:02:38.120 | but we can really credit Dr. Feldman and his laboratory

00:02:40.800 | for identifying the particular brain areas

00:02:43.080 | that control different patterns of breathing

00:02:44.920 | and how that information can be leveraged

00:02:47.400 | towards health, high performance, and for combating disease.

00:02:51.060 | So today's conversation,

00:02:52.360 | you're going to learn a tremendous amount

00:02:54.400 | from the top researcher in this field.

00:02:56.580 | It's a really wonderful and special opportunity

00:02:58.420 | to be able to share his knowledge with you.

00:03:00.580 | And I know that you're not only going to enjoy it,

00:03:02.800 | but you are going to learn a tremendous amount.

00:03:05.180 | Before we begin, I'd like to emphasize that this podcast

00:03:07.600 | is separate from my teaching and research roles at Stanford.

00:03:10.320 | It is, however, part of my desire and effort

00:03:12.200 | to bring zero cost to consumer information about science

00:03:14.680 | and science-related tools to the general public.

00:03:17.200 | In keeping with that theme,

00:03:18.160 | I'd like to thank the sponsors of today's podcast.

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00:09:20.280 | One quick mention before we dive

00:09:21.520 | into the conversation with Dr. Feldman.

00:09:23.680 | During today's episode,

00:09:24.840 | we discuss a lot of breathwork practices.

00:09:26.840 | And by the end of the episode,

00:09:28.040 | all of those will be accessible to you.

00:09:30.000 | However, I'm aware that there are a number

00:09:31.520 | of people out there that want to go even further

00:09:33.800 | into the science and practical tools of breathwork.

00:09:36.400 | And for that reason, I want to mention a resource to you.

00:09:39.200 | There is a cost associated with this resource,

00:09:41.040 | but it's a terrific platform

00:09:42.300 | for learning about breathwork practices

00:09:43.960 | and for building a number of different routines

00:09:46.240 | that you can do or that you could teach.

00:09:48.160 | It's called Our Breathwork Collective.

00:09:50.780 | I'm not associated with the Breathwork Collective,

00:09:53.000 | but Dr. Feldman is an advisor to the group

00:09:55.360 | and they offer daily live guided breathing sessions

00:09:58.140 | and an on-demand library that you can practice anytime,

00:10:01.120 | free workshops on breathwork.

00:10:02.700 | And these are really developed by experts in the field,

00:10:04.880 | including Dr. Feldman.

00:10:06.540 | So as I mentioned, I'm not on their advisory board,

00:10:08.720 | but I do know them in their work

00:10:10.220 | and it is of the utmost quality.

00:10:11.980 | So anyone wanting to learn or teach breathwork

00:10:14.040 | could really benefit from this course, I believe.

00:10:16.120 | If you'd like to learn more,

00:10:17.000 | you can click on the link in the show notes

00:10:18.820 | or visit ourbreathcollective.com/huberman

00:10:21.800 | and use the code Huberman at checkout.

00:10:23.760 | And if you do that,

00:10:24.780 | they'll offer you $10 off the first month.

00:10:26.840 | Again, it's ourbreathcollective.com/huberman

00:10:29.660 | to access the Our Breath Collective.

00:10:31.920 | And now for my conversation with Dr. Jack Feldman.

00:10:35.840 | Thanks for joining me today.

00:10:37.080 | - It's a pleasure to be here, Andrew.

00:10:38.820 | - Yeah, it's been a long time coming.

00:10:40.380 | You're my go-to source for all things respiration.

00:10:43.840 | I mean, I breathe on my own,

00:10:45.040 | but when I want to understand how I breathe

00:10:47.580 | and how the brain and breathing interact,

00:10:51.160 | you're the person I call.

00:10:52.640 | - Well, I'll do my best.

00:10:53.580 | As you know, there's a lot that we don't understand,

00:10:55.720 | which still keeps me employed and engaged,

00:10:58.080 | but we do know a lot.

00:11:00.780 | - Why don't we start off by just talking about

00:11:03.200 | what's involved in generating breath?

00:11:06.320 | And if you would,

00:11:08.320 | could you comment on some of the mechanisms

00:11:11.020 | for rhythmic breathing versus non-rhythmic breathing?

00:11:15.560 | - Okay, so on the mechanical side,

00:11:18.920 | which is obvious to everyone,

00:11:20.560 | we want to have air flow in, inhale,

00:11:24.880 | and we need to have air flow out.

00:11:26.720 | And the reason we'd need to do this

00:11:28.960 | is because for body metabolism, we need oxygen.

00:11:33.340 | And when oxygen is utilized

00:11:36.080 | through the aerobic metabolic process,

00:11:39.680 | we produce carbon dioxide.

00:11:41.100 | And so we have to get rid of the carbon dioxide

00:11:43.280 | that we produce, in particular because the carbon dioxide

00:11:46.820 | affects the acid-base balance of the blood, the pH.

00:11:50.440 | And all living cells are very sensitive

00:11:54.260 | to what the pH value is.

00:11:55.600 | So your body is very interested in regulating that pH.

00:11:59.120 | So we have to have enough oxygen for our normal metabolism,

00:12:03.520 | and we have to get rid of the CO2 that we produce.

00:12:06.420 | So how do we generate this air flow?

00:12:09.160 | Well, the air comes into the lungs.

00:12:11.240 | We have to expand the lungs.

00:12:12.880 | And as the lungs expand,

00:12:14.840 | basically it's like a balloon that you would pull apart.

00:12:17.960 | The pressure inside that balloon drops,

00:12:20.700 | and air will flow into the balloon.

00:12:22.220 | So we put pressure on the lung to pull it apart,

00:12:27.220 | that lowers the pressure in the air sacs called alveoli,

00:12:31.820 | and air will flow in because pressure outside the body

00:12:35.180 | is higher than pressure inside the body

00:12:37.140 | when you're doing this expansion, when you're inhaling.

00:12:40.400 | What produces that?

00:12:42.700 | Well, the principal muscle is the diaphragm,

00:12:45.820 | which is sitting inside the body just below the lung.

00:12:49.300 | And when you want to inhale,

00:12:51.540 | you basically contract the diaphragm, and it pulls it down.

00:12:55.060 | And as it pulls it down,

00:12:56.700 | it's inserting pressure forces on the lung.

00:12:59.620 | The lung wants to expand.

00:13:01.340 | At the same time, the rib cage is gonna rotate up and out,

00:13:06.140 | and therefore expanding the cavity, the thoracic cavity.

00:13:10.000 | At the end of inspiration,

00:13:13.620 | under normal conditions when you're at rest,

00:13:16.100 | you just relax, and it's like pulling on a spring.

00:13:19.220 | You pull down a spring, and you let go, and it relaxes.

00:13:21.740 | So you inhale, and you exhale.

00:13:25.840 | Inhale, relax, and exhale.

00:13:27.820 | - So the exhale is passive?

00:13:29.620 | - At rest, it's passive.

00:13:31.220 | We'll get into what happens when you need to increase

00:13:35.580 | the amount of air you're bringing in

00:13:37.720 | because your ventilation,

00:13:39.780 | your metabolism goes up like during exercise.

00:13:42.420 | Now, the muscles themselves,

00:13:45.340 | the skeletal muscles don't do anything unless

00:13:49.180 | the nervous system tells them to do something.

00:13:52.520 | And when the nervous system tells them to do something,

00:13:55.540 | they contract.

00:13:56.940 | So there are specialized neurons in the spinal cord,

00:14:00.700 | and then above the spinal cord,

00:14:02.180 | the region called the brain stem,

00:14:04.000 | which go to respiratory muscles,

00:14:07.140 | in particular for inspiration, the diaphragm,

00:14:09.660 | and the external intercostal muscles in the rib cage,

00:14:13.980 | and they contract.

00:14:15.460 | So these respiratory muscles,

00:14:17.740 | these inspiratory muscles become active.

00:14:22.420 | And they become active for a period of time,

00:14:25.700 | then they become silent, and when they become silent,

00:14:29.380 | the muscles then relax back to their original resting level.

00:14:33.020 | Where does that activity in these neurons

00:14:37.560 | that innervate the muscle, which are called motor neurons,

00:14:39.860 | where does that originate?

00:14:41.840 | Well, this was a question that's been bandied around

00:14:45.760 | for thousands of years.

00:14:47.820 | And when I was a beginning assistant professor,

00:14:52.740 | it was fairly high priority for me

00:14:55.560 | to try and figure that out because I wanted to understand

00:14:58.840 | where this rhythm of breathing was coming from,

00:15:01.920 | and you couldn't know where it was coming from

00:15:04.280 | until you knew where it was coming from.

00:15:07.080 | And I didn't phrase that properly.

00:15:08.660 | You couldn't understand how it was being done

00:15:10.920 | until you know where to look.

00:15:12.780 | So we did a lot of experiments, which I can go into detail,

00:15:16.040 | and finally found there was a region in the brainstem,

00:15:20.040 | that's once again this region sort of above the spinal cord,

00:15:24.020 | which was critical for generating this rhythm.

00:15:27.300 | It's called the pre-Butzinger complex,

00:15:29.340 | and we can talk about how that was named.

00:15:31.340 | This small site, which contains in humans

00:15:35.940 | a few thousand neurons, it's located on either side,

00:15:40.260 | and it works in tandem.

00:15:42.160 | And every breath begins with neurons in this region

00:15:47.160 | beginning to be active.

00:15:50.560 | And those neurons then connect ultimately

00:15:53.540 | to these motor neurons going to the diaphragm

00:15:56.560 | and to the external intercostals,

00:15:58.780 | causing them to be active

00:15:59.960 | and causing this inspiratory effort.

00:16:02.600 | When the neurons in the pre-Butzinger complex

00:16:06.980 | finish their burst of activity,

00:16:09.680 | then inspiration stops, and then you begin to exhale

00:16:14.680 | because of this passive recall of the lung and rib cage.

00:16:19.980 | - Could I just briefly interrupt you

00:16:22.400 | to ask a few quick questions before we move forward

00:16:26.160 | in this very informative answer?

00:16:29.740 | The two questions are, is there anything known

00:16:34.740 | about the activation of the diaphragm

00:16:38.340 | and the intercostal muscles between the ribs

00:16:40.820 | as it relates to nose versus mouth breathing?

00:16:44.220 | Or are they activated in the equivalent way,

00:16:48.700 | regardless of whether or not someone is breathing

00:16:50.400 | through their nose or mouth?

00:16:51.780 | - I don't think we fully have the answer to that.

00:16:55.880 | Clearly, there are differences

00:16:57.140 | between nasal and mouth breathing.

00:16:59.700 | At rest, the tendency is to do nasal breathing

00:17:04.780 | because the air flows that are necessary

00:17:08.460 | for normal breathing are easily managed

00:17:12.140 | by passing through the nasal cavities.

00:17:14.660 | However, when your ventilation needs to increase,

00:17:17.420 | like during exercise, you need to move more air,

00:17:20.340 | you do that through your mouth

00:17:22.040 | because the airways are much larger then,

00:17:24.740 | and therefore you can move much more air.

00:17:26.900 | But at the level of the intercostals and the diaphragm,

00:17:30.620 | their contraction is almost agnostic

00:17:35.620 | to whether or not the nose and mouth are open.

00:17:39.380 | - Okay, so if I understand correctly,

00:17:42.140 | there's no reason to suspect that there are particular,

00:17:45.420 | perhaps even non-overlapping sets of neurons

00:17:47.660 | in pre-Butzinger area of the brainstem

00:17:50.580 | that trigger nasal versus mouth inhales?

00:17:53.960 | - No, I would say that it's not

00:17:59.500 | that the pre-Butzinger complex is not concerned

00:18:01.940 | and cannot influence that,

00:18:03.780 | but it does not appear as if there's any

00:18:06.500 | modulation of whether or not it's,

00:18:10.420 | where the air is coming from,

00:18:11.800 | whether it's coming through your nasal passages

00:18:13.880 | or through your mouth.

00:18:15.500 | - Thank you, and then the other question I have

00:18:16.920 | is that these intercostal muscles between the ribs

00:18:19.360 | that move the ribs up and out, if I understand correctly,

00:18:21.860 | and the diaphragm, are those skeletal,

00:18:25.540 | or as the Brits would say, skeletal muscles,

00:18:28.740 | or smooth muscles?

00:18:30.220 | What type of muscle are we talking about here?

00:18:33.300 | - As I said earlier, these are skeletal,

00:18:35.740 | I didn't say they were skeletal muscles,

00:18:37.160 | but they're muscles that need neural input

00:18:40.100 | in order to move.

00:18:41.340 | You talked about smooth muscles.

00:18:43.700 | They're specialized muscles like we have in the gut

00:18:46.380 | and in the heart, and these are muscles that are capable

00:18:49.740 | of actually contracting and relaxing on their own.

00:18:54.420 | So the heart beats.

00:18:55.980 | It doesn't need neural input in order to beat.

00:18:58.700 | The neural inputs modulate the strength of it

00:19:02.160 | and the frequency, but they beat on their own.

00:19:05.080 | The skeletal muscles involved in breathing

00:19:09.060 | need neural input.

00:19:11.460 | Now, there are smooth muscles that have an influence

00:19:13.920 | on breathing, and these are muscles that are lining

00:19:16.500 | the airways, and so the airways have smooth muscle,

00:19:21.500 | and when they become activated, the smooth muscle

00:19:25.500 | can contract or relax, and when they contract inappropriately

00:19:30.500 | is when you have problems breathing like in asthma.

00:19:34.780 | Asthma is a condition where you get inappropriate

00:19:37.100 | constriction of the smooth muscles of the airways.

00:19:40.880 | - So there's no reason to think that in asthma,

00:19:42.660 | that the pre-bot singer or these other neuronal centers

00:19:45.500 | in the brain that activate breathing,

00:19:47.820 | that they are involved or causal for things like asthma?

00:19:52.500 | - As of now, I would say the preponderance of evidence

00:19:55.500 | is that it's not involved, but we've not really

00:19:58.180 | fully investigated that.

00:19:59.680 | - Thank you.

00:20:00.520 | Sorry to break your flow, but I was terribly interested

00:20:04.140 | in knowing answers to those questions,

00:20:06.260 | and you provided them, so thank you.

00:20:08.060 | - Now, remind me again where I was in my--

00:20:11.740 | - We were just landing in pre-bot singer,

00:20:14.220 | and we will return to the naming of pre-bot singer

00:20:17.460 | 'cause it's a wonderful and important story, really,

00:20:20.340 | that I think people should be aware of.

00:20:22.540 | But yeah, maybe you could march us through the brain centers

00:20:27.180 | that you've discovered and others have worked on as well

00:20:31.740 | that control breathing, pre-bot singer

00:20:33.520 | as well as related structures.

00:20:35.700 | - So when we discovered the pre-bot singer,

00:20:39.500 | we thought that it was the primary source

00:20:42.820 | of all rhythmic respiratory movements,

00:20:45.780 | both inspiration and expiration.

00:20:49.000 | The notion of a single source is like day or night.

00:20:53.860 | It's like they're all coming, they all have the same origin

00:20:56.940 | that the Earth rotates and day follows night.

00:20:59.600 | And we thought that the pre-bot singer complex

00:21:01.860 | would be inhalation, exhalation.

00:21:04.860 | And then in a series of experiments we did

00:21:10.020 | in the early part of 2000, we discovered

00:21:14.280 | that there seemed to be another region

00:21:17.180 | which was dominant in producing expiratory movements,

00:21:21.420 | that is the exhalation.

00:21:22.980 | We had made a fundamental mistake

00:21:28.580 | with the discovery of the pre-bot singer

00:21:32.620 | not taking into account that at rest

00:21:35.180 | expiratory muscle activity or exhalation is passive.

00:21:39.480 | So if that's the case, a group of neurons

00:21:44.600 | that might generate active expiration,

00:21:47.720 | that is to contract the expiratory muscles

00:21:50.040 | like the abdominal muscles or the internal intercostals

00:21:53.280 | are just silent.

00:21:54.820 | We just thought it wasn't there, it was coming

00:21:56.800 | from one place.

00:21:58.480 | But we got evidence that in fact it may have been coming

00:22:01.760 | from another place.

00:22:03.180 | And following up on these experiments,

00:22:04.880 | we discovered that there was a second oscillator

00:22:08.400 | and that oscillator is involved in generating

00:22:12.440 | what we call active expiration.

00:22:14.880 | That is this active.

00:22:16.560 | - Like if I go shh.

00:22:17.760 | - Yeah, or when you begin to exercise,

00:22:21.120 | you have to go, and actually move that air out.

00:22:25.220 | This group of cells, which is silent at rest,

00:22:28.860 | suddenly becomes active to drive those muscles.

00:22:32.120 | And it appears that it's an independent oscillator.

00:22:36.320 | - Maybe you could just clarify for people

00:22:37.520 | what an oscillator is.

00:22:39.080 | - Okay, an oscillator is something that goes

00:22:42.200 | in a cycle.

00:22:43.560 | So you can have a pendulum as an oscillator

00:22:45.760 | going back and forth.

00:22:47.200 | The earth is an oscillator because it goes around

00:22:49.680 | and it's day and night.

00:22:50.760 | - Some people's moods are oscillating.

00:22:52.640 | - Oscillating.

00:22:53.480 | And it depends how regular they are.

00:22:56.240 | You can have oscillators that are highly regular

00:22:58.240 | that are in a watch, or you can have those

00:23:01.400 | that are sporadic or episodic.

00:23:04.240 | Breathing is one of those oscillators that for life

00:23:08.100 | has to be working continuously, 24/7.

00:23:11.720 | It starts late in the third trimester

00:23:14.320 | because it has to be working when you're born,

00:23:16.840 | and basically works throughout life.

00:23:19.240 | And if it stops, if there's no intervention

00:23:22.320 | beyond a few minutes, it will likely be fatal.

00:23:25.800 | - What is this second oscillator called?

00:23:28.480 | - Well, we found it in a region around the facial nucleus.

00:23:33.480 | So we initially, when this region was initially identified,

00:23:41.160 | we thought it was involved in sensing carbon dioxide.

00:23:45.440 | It was what we call a central chemoreceptor.

00:23:48.000 | That is, we wanna keep carbon dioxide levels,

00:23:50.600 | particularly in the brain, at a relatively stable level

00:23:53.960 | 'cause the brain is extraordinarily sensitive

00:23:56.400 | to changes in pH.

00:23:58.240 | If there's a big shift in carbon dioxide,

00:24:01.520 | there'd be a big shift in brain pH,

00:24:03.480 | and that'll throw your brain, if I can use

00:24:06.240 | the technical term, out of whack.

00:24:08.840 | And so you wanna regulate that.

00:24:11.000 | The way to regulate something in the brain

00:24:13.760 | is you have a sensor in the brain.

00:24:15.800 | And others basically identified that the ventral surface

00:24:20.440 | of the brainstem, that is the part of the brainstem

00:24:22.760 | that's on this side, was critical for that.

00:24:27.520 | And then we identified a structure

00:24:30.520 | that was near the trapezoid nucleus.

00:24:35.200 | It was not named in any of these neuroanatomical atlases.

00:24:39.240 | So we just picked the name out of the hat

00:24:41.480 | and we called it the retrotrapezoid nucleus.

00:24:44.520 | - I should clarify for people,

00:24:45.600 | when Jack is saying trapezoid,

00:24:48.320 | it doesn't mean the trapezoid muscles.

00:24:49.640 | Trapezoid refers to the shape of this nucleus,

00:24:52.960 | this cluster of neurons.

00:24:54.240 | Para-facial makes me think that this general area

00:24:58.800 | is involved in something related to mouth or face.

00:25:02.600 | Is it an area rich with neurons

00:25:06.280 | controlling other parts of the face?

00:25:08.080 | Eye blinks, nose twitches, lip curls, lip smacks?

00:25:12.920 | - If you go back in an evolutionary sense,

00:25:15.360 | and a lot of things that are hard to figure out

00:25:18.760 | begin to make sense when you look at the evolution

00:25:21.600 | of the nervous system.

00:25:23.240 | When control of facial muscles going back

00:25:28.080 | to more primitive creatures,

00:25:29.320 | because they had to take things in their mouth for eating.

00:25:33.320 | So we call that the face sort of developed.

00:25:36.720 | The eyes were there, the mouth is there.

00:25:38.960 | These nuclei that contained the motor neurons,

00:25:43.920 | a lot of the control systems for them

00:25:46.320 | developed in the immediate vicinity.

00:25:49.080 | So if you think about the face,

00:25:50.880 | there's a lot of subnuclei around there

00:25:54.080 | that had various roles at various different times

00:25:56.640 | in evolution.

00:25:57.840 | And at one point in evolution,

00:26:00.480 | the facial muscles were probably very important

00:26:03.320 | in moving fluid in and out of the mouth

00:26:06.440 | and moving air in and out of the mouth.

00:26:08.920 | And so part of these many different subnuclei

00:26:13.560 | now seems to be in mammals to be involved

00:26:16.760 | in the control of expiratory muscles.

00:26:19.200 | But we have to remember that mammals are very special

00:26:24.000 | when it comes to breathing,

00:26:25.200 | because we're the only class of vertebrates

00:26:28.480 | that have a diaphragm.

00:26:30.440 | If you look at amphibians and reptiles,

00:26:33.480 | they don't have a diaphragm.

00:26:35.280 | And the way they breathe is not by actively inspiring

00:26:39.440 | and passively expiring.

00:26:41.480 | They breathe by actively expiring and passively inspiring

00:26:46.160 | because they don't have a powerful inspiratory muscle.

00:26:50.560 | And somewhere along the line, the diaphragm developed.

00:26:55.560 | And there are lots of theories about how it developed.

00:26:58.280 | I don't think it's particularly clear.

00:26:59.760 | There was something you can find in alligators and lizards.

00:27:05.320 | That could have turned into a muscle that was a diaphragm.

00:27:08.920 | The amazing thing about the diaphragm

00:27:12.280 | is that it's mechanically extremely efficient.

00:27:15.960 | And what do I mean by that?

00:27:17.680 | Well, if you look at how oxygen gets from outside the body

00:27:22.160 | into the bloodstream, the critical passage

00:27:27.000 | is across the membrane in the lung.

00:27:29.920 | It's called the alveolar capillary membrane.

00:27:33.080 | The alveolus is part of the lung

00:27:36.440 | and the blood runs through capillaries,

00:27:38.960 | which are the smallest tubes in the circulatory system.

00:27:42.600 | And at that point, oxygen can go from the air-filled alveolus

00:27:47.600 | into the blood.

00:27:50.320 | - Which is amazing.

00:27:51.880 | I find that amazing.

00:27:52.920 | Even though it's just purely mechanical,

00:27:54.600 | the idea that we have these little sacs in our lungs,

00:27:56.320 | we inhale and the air goes in

00:27:57.740 | and literally the oxygen can pass into the bloodstream.

00:28:01.000 | - Passes into the bloodstream.

00:28:02.480 | But the rate at which it passes

00:28:05.200 | will depend on the characteristics of the membrane,

00:28:08.600 | what the distance is between the alveolus

00:28:11.960 | and the blood vessel, the capillary.

00:28:14.720 | But the key element is the surface area.

00:28:19.000 | The bigger the surface area,

00:28:20.800 | the more oxygen that can pass through.

00:28:23.320 | It's entirely a passive process.

00:28:25.240 | There's no magic about making oxygen go in.

00:28:28.700 | Now, how do you pack a large surface area in a small chest?

00:28:33.700 | Well, you start out with one tube, which is the trachea.

00:28:37.900 | The trachea expands.

00:28:39.840 | Now you have two tubes.

00:28:41.840 | Then you have four tubes and it keeps branching.

00:28:45.340 | At some point, at the end of those branches,

00:28:48.580 | you put a little sphere, which is an alveolus.

00:28:52.060 | And that determines what the surface area is going to be.

00:28:56.400 | Now, you then have a mechanical problem.

00:28:59.640 | You have the surface area.

00:29:01.340 | You have to be able to pull it apart.

00:29:03.540 | So imagine you have a little square of elastic membrane.

00:29:08.140 | It doesn't take a lot of force to pull it apart.

00:29:11.020 | But now if you increase it by 50 times,

00:29:14.620 | you need a lot more force to pull it apart.

00:29:17.020 | So amphibians who were breathing,

00:29:19.860 | not by compressing the lungs

00:29:21.780 | and then just passively expanding it,

00:29:24.980 | weren't able to generate a lot of force.

00:29:27.280 | So they have relatively few branches.

00:29:29.600 | So if you look at the surface area

00:29:31.600 | that they pack in their lungs,

00:29:34.260 | relative to their body size, it's not very impressive.

00:29:38.580 | Whereas when you get to mammals,

00:29:41.320 | the amount of branching that you have

00:29:44.520 | is you have four to 500 million alveoli.

00:29:48.880 | - If we were to take those four to five million alveoli-

00:29:51.840 | - 100 million, 400 to 500 million.

00:29:54.760 | - 100 million, excuse me, and lay those out flat,

00:29:58.220 | what sort of surface area are we talking about?

00:30:00.020 | - About 70 square meters,

00:30:02.020 | which is about a third the size of a tennis court.

00:30:04.960 | - Wow.

00:30:05.800 | - So you have a membrane inside of you,

00:30:07.240 | a third the size of a tennis court,

00:30:09.400 | that you actually have to expand every breath.

00:30:12.680 | And you do that without exerting much of a,

00:30:15.480 | you don't feel it.

00:30:16.780 | And that's because you have this amazing muscle,

00:30:19.020 | the diaphragm, which because of its positioning,

00:30:22.360 | just by moving two thirds of an inch down

00:30:26.360 | is able to expand that membrane enough

00:30:29.460 | to move air into the lungs.

00:30:31.760 | Now, at rest, the volume of air in your lungs

00:30:36.760 | is about two and a half liters.

00:30:40.280 | Do we need to convert that to courts?

00:30:42.380 | - No.

00:30:43.220 | - All right, it's about two and a half liters.

00:30:45.320 | When you take a breath,

00:30:47.080 | you're taking another 500 milliliters or half a liter.

00:30:50.680 | That's the size maybe a little of my fist.

00:30:53.820 | So you're increasing the volume by 20%,

00:30:58.120 | but you're doing that by pulling

00:31:00.100 | on this 70 square meter membrane.

00:31:02.920 | But that's enough to bring enough fresh air into the lung

00:31:07.020 | to mix in with the air that's already there,

00:31:09.600 | that the oxygen levels in your bloodstream

00:31:13.720 | goes from a partial pressure of oxygen,

00:31:18.000 | which is 40 millimeters of mercury

00:31:20.180 | to 100 millimeters of mercury.

00:31:23.120 | So that's a huge increase in oxygen

00:31:25.600 | and that's enough to sustain normal metabolism.

00:31:28.940 | So we have this amazing mechanical advantage

00:31:33.940 | by having a diaphragm.

00:31:37.640 | - Do you think that our brains are larger

00:31:40.580 | than that of other mammals in part

00:31:42.920 | because of the amount of oxygen

00:31:44.180 | that we have been able to bring into our system?

00:31:46.800 | - I would say a key step in the ability

00:31:50.500 | to develop a large brain that has a continuous demand

00:31:54.700 | for oxygen is the diaphragm.

00:31:57.520 | Without a diaphragm, you're an amphibian.

00:32:01.000 | And there's another solution to increasing oxygen uptake,

00:32:06.000 | which is the way birds breathe,

00:32:09.780 | but birds have other limitations

00:32:12.000 | and they still can't get brains as big as mammals have.

00:32:16.160 | The brain utilizes maybe 20% of all the oxygen

00:32:24.160 | that we intake and it needs it continuously.

00:32:27.720 | The brain doesn't wanna be neglected.

00:32:29.920 | So this puts certain demands on breathing system.

00:32:32.800 | In other words, you can't shut it down for a while,

00:32:35.440 | which poses other issues.

00:32:38.000 | You're born and you have to mature.

00:32:40.520 | You have the small body, you have a small lung,

00:32:43.200 | you have a very pliant rib cage,

00:32:46.120 | and now you have to develop into an adult

00:32:48.200 | which has a stiffer rib cage.

00:32:50.120 | And so there are changes happening in your brain

00:32:52.760 | and your body where breathing,

00:32:54.880 | the neural control of breathing has to change on the fly.

00:32:58.660 | It's not like for things like vision

00:33:01.520 | where you have the opportunity to sleep.

00:33:04.800 | And while you're sleeping,

00:33:05.880 | the brain is capable of doing things

00:33:07.520 | that are not easy to do during wakefulness,

00:33:09.620 | like the construction crew comes in during sleep.

00:33:12.720 | Breathing has been,

00:33:14.000 | the change in breathing have been described

00:33:16.000 | as trying to build an airplane while it's flying.

00:33:20.620 | - Basically what Jack is saying

00:33:21.760 | is that respiration science is more complex

00:33:25.720 | and hardworking than vision science,

00:33:27.280 | which is a direct jab at me

00:33:29.540 | that some of you might've missed,

00:33:30.560 | but I definitely did not miss.

00:33:32.120 | And I appreciate that you always take the opportunity

00:33:35.040 | like a good New Yorker to give me

00:33:37.600 | a good, healthy, intellectual jab.

00:33:40.640 | A question related to diaphragmatic breathing

00:33:45.120 | versus non-diaphragmatic breathing,

00:33:46.620 | because the way you describe it,

00:33:48.000 | the diaphragm is always involved.

00:33:49.760 | But over the years,

00:33:51.820 | whether it be for yoga class or a breath work thing,

00:33:56.580 | or you hear online that we should be breathing

00:33:59.340 | with our diaphragm,

00:34:00.300 | that rather than lifting our rib cage when we breathe

00:34:03.760 | and our chest, that it is healthier, in air quotes,

00:34:06.600 | or better somehow to have the belly expand when we inhale.

00:34:11.160 | I'm not aware of any particular studies

00:34:13.180 | that have really examined the direct health benefits

00:34:16.180 | of diaphragmatic versus non-diaphragmatic breathing.

00:34:19.120 | But if you don't mind commenting on anything you're aware of

00:34:24.120 | as it relates to diaphragmatic

00:34:25.400 | versus non-diaphragmatic breathing,

00:34:27.380 | whether or not people tend to be diaphragmatic breathers

00:34:29.880 | by default, et cetera,

00:34:31.240 | that would be, I think, interesting to a number of people.

00:34:34.080 | Well, I think by default, we are obligate diaphragm breathers.

00:34:37.520 | There may be pathologies where the diaphragm is compromised

00:34:42.840 | and you have to use other muscles,

00:34:45.360 | and that's a challenge.

00:34:47.500 | It certainly,

00:34:50.800 | at rest, other muscles can take over.

00:34:56.260 | But if you need to increase your ventilation,

00:35:00.160 | the diaphragm is very important.

00:35:02.840 | It would be hard to increase your ventilation otherwise.

00:35:05.360 | - Do you pay attention to whether or not

00:35:06.920 | you are breathing in a manner where your belly

00:35:09.320 | goes out a little bit as you inhale?

00:35:12.860 | Because I can do it both ways, right?

00:35:14.120 | I can inhale, bring my belly in,

00:35:16.440 | or I can inhale, push my diaphragm and belly out,

00:35:21.260 | not the diaphragm out.

00:35:23.080 | And that's interesting, right?

00:35:24.060 | Because it's a completely different muscle set

00:35:25.840 | for each version.

00:35:28.260 | - Well, in the context of things like breath practice,

00:35:33.260 | I'm a bit agnostic about the effects

00:35:37.540 | of some of the different patterns of breathing.

00:35:40.580 | Clearly, some are gonna work through different mechanisms,

00:35:44.780 | and we can talk about that.

00:35:46.660 | But at a certain level, for example,

00:35:48.500 | whether it's primarily diaphragm

00:35:50.720 | where you move your abdomen or not,

00:35:52.940 | I am agnostic about it.

00:35:55.620 | I think that the changes that breathing induces

00:36:00.260 | in emotion and cognition,

00:36:02.540 | I have different ideas about what the influence is.

00:36:06.920 | And I don't see that primarily as how,

00:36:11.220 | which particular muscles you're choosing.

00:36:14.140 | But that just could be my own prejudice.

00:36:17.100 | - Okay.

00:36:17.940 | And we will return to that as a general theme

00:36:21.860 | in a little bit.

00:36:22.700 | I wanna ask you about sighing.

00:36:25.780 | One of the many great gifts that you've given us

00:36:30.780 | over the years is an understanding of these things

00:36:35.460 | that we call physiological sighs.

00:36:38.260 | Could you tell us about physiological sighs,

00:36:40.380 | what's known about them,

00:36:42.380 | what your particular interest in them is,

00:36:45.820 | and what they're good for?

00:36:47.560 | - Very interesting and important question.

00:36:52.260 | So everyone has a sense of what a sigh is.

00:36:57.260 | We certainly, when we're emotional in some ways,

00:37:02.140 | we're stressed, we're particularly happy,

00:37:04.860 | we'll take a, we'll sigh.

00:37:07.180 | It turns out that we're sighing all the time.

00:37:12.600 | And when I would ask people

00:37:16.140 | who are not particularly knowledgeable

00:37:17.980 | that haven't read my papers or James Nestor's book

00:37:20.800 | or listened to your podcast,

00:37:22.980 | they're usually off by two orders of magnitude

00:37:27.080 | about how frequently we sigh on the low side.

00:37:30.260 | In other words, they say once an hour, 10 times a day.

00:37:35.260 | We sigh about every five minutes.

00:37:38.700 | And I would encourage anyone who finds that

00:37:42.660 | to be a unbelievable fact is to lie down in a quiet room

00:37:48.860 | and just breathe normally, just relax, just let go,

00:37:53.100 | and just pay attention to your breathing.

00:37:55.840 | And you'll find that every couple of minutes

00:37:58.060 | you're taking a deep breath and you can't stop it.

00:38:03.060 | You know, it just happens.

00:38:05.680 | Now why?

00:38:07.020 | Well, we have to go back to the lung again.

00:38:09.480 | The lung has these 500 million alveoli

00:38:12.680 | and they're very tiny.

00:38:14.380 | They're 200 microns across.

00:38:18.980 | So they're really, really tiny.

00:38:21.180 | And you can think of them as fluid-filled.

00:38:24.100 | They're fluid-lined.

00:38:25.220 | And the reason they're fluid-lined

00:38:26.580 | has to do with the esoterica of the mechanics of that.

00:38:31.580 | It makes it a little easier to stretch them

00:38:34.340 | with this fluid line, which is called surfactant.

00:38:37.640 | And surfactant is important during development.

00:38:39.860 | It is a determining factor when premature infants are born.

00:38:45.900 | If they do not have lung surfactant,

00:38:48.620 | it makes it much more challenging to take care of them

00:38:52.020 | than after they have lung surfactant,

00:38:53.620 | which is sometime, if I remember correctly,

00:38:55.860 | in the late second, early third trimester, which it appears.

00:38:59.820 | In any case, it's fluid-lined.

00:39:01.780 | Now think of a balloon that you would blow up,

00:39:06.100 | but now before you blow it up, fill the balloon with water.

00:39:09.180 | Squeeze all the water out.

00:39:11.660 | And now when you squeeze all the water out,

00:39:15.260 | you notice the size of the balloons stick to each other.

00:39:18.300 | Why is that?

00:39:19.420 | Well, that's because water has what's called surface tension

00:39:23.260 | and when you have two surfaces of water together,

00:39:26.940 | they actually tend to stick to each other.

00:39:29.420 | Now, when you try and blow that balloon up,

00:39:31.900 | you know that it, or you'll notice

00:39:34.080 | if you've ever done it before,

00:39:35.620 | that the balloon is a little harder to inflate

00:39:39.000 | than if we're dry on the inside.

00:39:40.900 | Why is that?

00:39:41.740 | Because you have to overcome that surface tension.

00:39:45.740 | Well, your alveoli have a tendency to collapse.

00:39:50.740 | There's 500 million of them.

00:39:53.080 | They're not collapsing at a very high rate,

00:39:55.500 | but it's a slow rate that's not trivial.

00:39:58.860 | And when an alveolus collapses,

00:40:01.340 | it no longer can receive oxygen or take carbon dioxide out.

00:40:06.340 | It's sort of taken out of the equation.

00:40:08.680 | Now, if you have 500 million of them and you lose 10,

00:40:11.820 | no big deal, but if they keep collapsing,

00:40:15.460 | you can lose a significant part

00:40:16.980 | of the surface area of your lung.

00:40:18.680 | Now, a normal breath is not enough to pop them open,

00:40:24.240 | but if you take a deep breath, it pops them open.

00:40:28.500 | - Through nose or mouth.

00:40:29.600 | - Doesn't matter, doesn't matter.

00:40:30.800 | Or it's just increased that lung volume

00:40:33.340 | 'cause you're just pulling on the lungs, they'll pop open.

00:40:37.700 | About every five minutes.

00:40:39.300 | And so we're doing it every five minutes

00:40:43.540 | in order to maintain the health of our lung.

00:40:45.740 | In the early days of mechanical ventilation,

00:40:49.580 | which was used to treat polio victims

00:40:52.760 | who had weakness of their respiratory muscles,

00:40:56.020 | they'd be put in these big steel tubes

00:41:00.060 | and the way they would work is that the pressure

00:41:02.760 | outside the body would drop.

00:41:05.100 | That would put a expansion pressure on the lungs,

00:41:09.100 | excuse me, on the rib cage.

00:41:10.300 | The rib cage would expand and then the lung would expand

00:41:13.900 | and then the pressure would go back to normal

00:41:16.020 | and the lung and rib cage would go back to normal.

00:41:19.760 | There was a, this was great for getting ventilation,

00:41:24.180 | but there was a relatively high mortality rate.

00:41:26.580 | It was a bit of a mystery and one solution

00:41:31.020 | was to just give bigger breaths.

00:41:33.580 | They gave bigger breaths and the mortality rate dropped.

00:41:35.860 | And it wasn't until, I think it was the '50s,

00:41:39.660 | where they realized that they didn't have to increase

00:41:41.860 | every breath to be big.

00:41:44.900 | What they needed to do is every so often

00:41:46.940 | they'd have one big breath.

00:41:49.180 | So you have a couple of minutes of normal breaths

00:41:51.140 | and then one big breath,

00:41:52.400 | just mimicking the physiological size

00:41:55.460 | and then the mortality rate dropped significantly.

00:41:58.080 | And if you see someone on a ventilator in the hospital,

00:42:03.800 | if you watch every couple of minutes

00:42:05.680 | that you see the membrane move up and down,

00:42:07.920 | every couple of minutes there'll be a super breath

00:42:10.280 | and that pops it open.

00:42:12.640 | So there are these mechanisms for these physiological size.

00:42:17.640 | So just like with the collapse of the lungs

00:42:20.620 | where you need a big pressure to pop it open,

00:42:25.360 | it's the same thing with the alveoli.

00:42:26.960 | You need a bigger pressure

00:42:28.760 | and a normal breath is not enough.

00:42:30.960 | So you have to take a big inhale. (exhales)

00:42:34.480 | And what nature has done is instead of requiring us

00:42:37.460 | to remember to do it, it does it automatically.

00:42:41.000 | And it does it about every five minutes.

00:42:43.440 | And one of the questions we asked is,

00:42:47.740 | how is this happening?

00:42:48.960 | Why every five minutes?

00:42:50.320 | What's doing it?

00:42:52.440 | And we got into it through a back door.

00:42:57.440 | Typical of the way a lot of science gets done,

00:43:00.660 | there's a serendipitous event where you run across a paper

00:43:05.660 | and something clicks and you just, you follow it up.

00:43:10.620 | Sometimes you go down blind ends,

00:43:12.420 | but this turned out to be incredibly productive.

00:43:15.260 | One of the guys in my lab was reading a paper about stress.

00:43:20.720 | And during stress, lots of things happen in the body.

00:43:24.320 | One of which is that the hypothalamus,

00:43:26.520 | which is very reactive to body state,

00:43:29.460 | releases peptides, which are specialized molecules

00:43:33.160 | which then circulate throughout the brain and body

00:43:36.080 | that have particular effects,

00:43:37.920 | usually to help deal better with the stress.

00:43:40.920 | And one class of the peptides that are released

00:43:43.460 | are called bombicin-related peptides.

00:43:45.560 | And he also realized, because he was a breathing guy,

00:43:51.800 | that when you stress, you sigh more.

00:43:54.640 | So we said, all right, maybe they're related.

00:43:59.000 | Bombicin is relatively cheap to buy.

00:44:02.500 | We said, let's buy some bombicin,

00:44:04.160 | throw it in the brain stem, let's see what happens.

00:44:07.660 | And one of the nice things about some experiments

00:44:12.660 | that we try to design is to fail quickly.

00:44:16.560 | So here we had the idea, we throw bombicin in

00:44:19.620 | and if bombicin did nothing,

00:44:21.640 | nothing lost, maybe $50 to buy the bombicin.

00:44:25.200 | But if it did something, it might be of some interest.

00:44:27.460 | So one afternoon, he did the experiment

00:44:30.440 | and he comes to me, he says,

00:44:33.060 | I won't quote exactly what he said

00:44:34.900 | because it might need to be censored,

00:44:37.280 | but he said, look at this.

00:44:39.780 | And it was in a rat.

00:44:42.460 | Rats sigh about every two minutes.

00:44:45.180 | They're smaller than we are

00:44:46.400 | and they need to sigh more often.

00:44:48.640 | Their sigh rate went from 20 to 30 per hour

00:44:54.320 | to 500 per hour when he put bombicin into

00:44:57.360 | the pre-Botsinger complex.

00:44:58.820 | - Amazing.

00:44:59.920 | - And the way he did that is he took a very,

00:45:02.620 | very fine glass needle and anesthetized a rat

00:45:07.620 | and inserted that needle directly

00:45:10.540 | into the pre-Botsinger complex.

00:45:12.440 | So it wasn't a generalized delivery of the peptide,

00:45:15.040 | it was localized to the pre-Botsinger

00:45:17.160 | and the sigh rate went through the roof.

00:45:20.040 | - And I would add that that was an important experiment

00:45:23.160 | to deliver the bombicin directly to that site

00:45:26.080 | because one could have concluded that the injection

00:45:29.160 | of the bombicin increased sign because it increased stress

00:45:32.720 | rather than directly increase sign.

00:45:34.960 | - Amongst hundreds of other possible interpretations.

00:45:37.800 | So the precision here is very important

00:45:40.320 | and that goes back to what I said at the very beginning.

00:45:43.160 | Knowing where this is happening allows you

00:45:45.520 | to do the proper investigations.

00:45:47.240 | If we didn't know where the inspiratory rhythm

00:45:49.500 | is originating, we never could have done this experiment.

00:45:53.180 | And so then we did another experiment.

00:45:55.860 | We said, okay, what happens if we take the cells

00:46:00.860 | in the pre-Botsinger that are responding to the peptide?

00:46:04.860 | So neurons will respond to a peptide

00:46:08.060 | because they have specialized receptors for that peptide.

00:46:11.740 | And not every neuron expresses those receptors.

00:46:15.260 | In the pre-Botsinger complex,

00:46:17.300 | it's probably a few hundred out of thousands.

00:46:20.560 | So we used the technique we had used before.

00:46:25.420 | And this is a technique developed by Doug Lappe

00:46:28.700 | down in San Diego where you could take a peptide

00:46:33.700 | and conjugate it with a molecule called saprin.

00:46:39.400 | Saprin is a plant-derived molecule

00:46:41.660 | which is a cousin to ricin.

00:46:44.220 | And many of your listeners may have heard of ricin.

00:46:47.820 | - It's a ribosomal toxin.

00:46:49.740 | - It's very nasty.

00:46:51.180 | A single stab with an umbrella will kill you,

00:46:56.540 | which is something that supposedly happened

00:46:59.340 | to a Bulgarian diplomat by a Russian operative

00:47:02.380 | on a bridge in London.

00:47:04.020 | He got stabbed.

00:47:04.940 | And the way ricin works is it goes inside a cell,

00:47:08.460 | crosses the cell membrane, goes inside the cell,

00:47:11.340 | kills the cell, then it goes to the next cell,

00:47:14.180 | and then the next cell, and then the next cell.

00:47:16.620 | It's extremely dangerous.

00:47:21.560 | In fact, it's firstly impossible to work on in a lab

00:47:24.100 | in the United States.

00:47:25.180 | They won't let you touch it. - Ricin.

00:47:26.660 | - Ricin.

00:47:27.500 | - 'Cause we've worked with saprin many times.

00:47:30.420 | - Saprin is safe because it doesn't cross cell membranes.

00:47:35.060 | So you get an injection of saprin,

00:47:37.220 | it won't do anything 'cause it stays outside of cells.

00:47:39.820 | Please, nobody do that,

00:47:41.220 | even though it doesn't cross cell membranes.

00:47:44.060 | Please, nobody inject saprin,

00:47:45.860 | whether or not you are a operative or otherwise.

00:47:49.020 | - Thank you, Andrew, for protecting me there.

00:47:51.340 | But what Doug Lappe figured out is that

00:47:56.860 | when a ligand binds to a receptor,

00:48:01.260 | that's when a molecule binds to its receptor,

00:48:04.200 | in many cases, that receptor ligand complex

00:48:09.020 | gets pulled inside the cell.

00:48:10.820 | So it goes from the membrane of the cell inside the cell.

00:48:13.420 | - It's sort of like you can't go to the dance alone,

00:48:15.060 | but if you're coupled up, you get in the door.

00:48:17.260 | - That's right.

00:48:18.160 | So what he figured out is he put saprin to the peptide,

00:48:23.060 | the peptide binds to its receptor, it gets internalized,

00:48:26.580 | and then when it's inside the cell,

00:48:28.740 | saprin does the same thing that ricin does.

00:48:31.760 | It kills the cell, but then it can't go into the next cell.

00:48:34.920 | So the only cells that get killed,

00:48:37.820 | or the more polite term, ablated,

00:48:40.340 | are cells that express that receptor.

00:48:43.940 | So if you have a big conglomeration of cells,

00:48:46.780 | you have a few thousand,

00:48:47.900 | and only 50 of them express that receptor,

00:48:51.940 | then you inject the saprin conjugated to the ligand,

00:48:55.440 | to the peptide, and only those 50 cells die.

00:48:58.100 | So we took bombicin conjugated to saprin,

00:49:03.680 | injected in the pre-butzinger complex of rats,

00:49:07.740 | and it took about a couple of days

00:49:10.860 | for the saprin to actually ablate cells.

00:49:14.860 | And what happened is that the mice started sighing

00:49:18.420 | less and less, excuse me, the rats started sighing less

00:49:22.860 | and less and less and less, and essentially stopped sighing.

00:49:26.640 | - So your student, or postdoc was it,

00:49:31.580 | murdered these cells, and as a consequence,

00:49:34.680 | the sighing goes away.

00:49:36.540 | What was the consequence of eliminating sighing

00:49:39.660 | on the internal state or the behavior of the rats?

00:49:44.660 | Did they, in other words, if one can't sigh,

00:49:49.980 | generate physiological sighs,

00:49:51.500 | what is the consequence on state of mind?

00:49:55.140 | You would imagine that carbon dioxide

00:49:57.060 | would build up more readily or to higher levels

00:50:00.220 | in the bloodstream,

00:50:01.660 | and that the animals would be more stressed.

00:50:04.300 | That's the kind of logical extension of the way

00:50:06.620 | we set it up.

00:50:07.660 | - It was less benign than that.

00:50:11.100 | When the animals got to the point where they weren't sighing,

00:50:14.460 | then, and we did not determine this,

00:50:19.260 | but the presumption was that their lung function

00:50:21.780 | significantly deteriorated, and their whole health

00:50:26.780 | deteriorated significantly, and we had to sacrifice them.

00:50:31.500 | So I can't tell you whether they were stressed or not,

00:50:35.420 | but their breathing got to be significantly

00:50:38.060 | deteriorated that we sacrificed them at that point.

00:50:44.420 | Now we don't know whether that is specifically related

00:50:48.140 | to the fact they didn't sigh,

00:50:50.220 | or that there was secondary damage due to the fact

00:50:53.460 | that some cells die, so we never determined that.

00:50:56.060 | Now, after we did this study,

00:51:00.660 | to be candid, it wasn't a high priority for us

00:51:04.180 | to get this out the door and publish it.

00:51:06.780 | So it stayed on the shelf.

00:51:08.260 | And then I got a phone call from a graduate student

00:51:13.300 | at Stanford, Kevin Yackel, who starts asking me

00:51:17.620 | all these interesting questions about breathing.

00:51:22.380 | And I'm happy to answer them, but at some point,

00:51:24.660 | it concerned me because he was working

00:51:27.780 | for a renowned biochemist who worked on lung

00:51:32.220 | in Drosophila, fruit flies, Mark Krasnow.

00:51:36.300 | - Yeah, got my next door colleague.

00:51:37.980 | - Right, and I said, "Why are you asking me this?"

00:51:41.820 | And he said, "I was an undergraduate at UCLA,

00:51:44.540 | "and you gave a lecture in my undergraduate class,

00:51:47.180 | "and I was curious about breathing ever since."

00:51:49.580 | So that's one of those things which, as a professor,

00:51:52.060 | you love to hear, that actually is something

00:51:54.700 | you really affected the life of a student.

00:51:56.660 | - Well, and you birthed a competitor,

00:51:57.980 | but you had only yourself to blame.

00:51:59.580 | - No, I don't look at that as a competitor.

00:52:02.220 | I think that there's enough interesting things to go on.

00:52:06.300 | I know some of our neuroscience colleagues say,

00:52:08.320 | "You can work on my lab, but then when you leave my lab,

00:52:11.040 | "you gotta work on something different."

00:52:12.500 | - No one I ever trained with said that.

00:52:14.260 | It's open field.

00:52:15.100 | You wanna work on something, you hop in the mix.

00:52:18.000 | - But there are people like that, neuroscientists like that.

00:52:21.360 | I never felt like that.

00:52:22.200 | - I hear that their breathing apparatus are disrupted,

00:52:24.380 | and it causes a brain dysfunction that leads to the behavior

00:52:27.060 | you just described.

00:52:28.280 | It's actually not true.

00:52:29.380 | But in terms of the, so before we talk about

00:52:35.740 | the beautiful story with Yackel and Krasnow and Feld lab,

00:52:41.480 | I want to just make sure that I understand.

00:52:46.180 | So if physiological sighs don't happen,

00:52:49.180 | basically breathing overall suffers.

00:52:54.260 | - Well, that would go back to the observations

00:52:56.660 | in polio victims in these iron lungs

00:52:59.260 | where the principle deficit was there was no hyperinflation

00:53:04.260 | in the lungs and many of them deteriorated and died.

00:53:07.960 | - And just to stay on this one more moment

00:53:10.620 | before we move to what you were about to describe,

00:53:14.040 | we hear often that people will overdose on drugs

00:53:19.060 | of various kinds because they stop breathing.

00:53:22.180 | So barbiturates, alcohol combined with barbiturates

00:53:25.080 | is a common cause of death for drug users

00:53:28.740 | and contraindications of drugs and these kinds of things.

00:53:32.300 | You hear all the time about celebrities dying

00:53:34.200 | because they combined alcohol with barbiturates.

00:53:37.480 | Is there any evidence that the sighs that occur

00:53:39.700 | during sleep or during states of deep, deep relaxation

00:53:43.700 | and sedation that sighs recover the brain?

00:53:52.300 | Because you could imagine that if these sighs don't happen

00:53:55.500 | as a consequence of some drug impacting these brain centers,

00:53:58.880 | that that could be one cause

00:54:00.260 | of basically asphyxiation and death.

00:54:03.300 | - If you look at the progression of any mammal to death,

00:54:08.300 | you find that their breathing slows down,

00:54:15.220 | a death due to quote natural causes.

00:54:18.160 | Their breathing slows down.

00:54:20.700 | It will stop and then they'll gasp.

00:54:23.960 | So we have the phrase dying gas, super large breaths.

00:54:28.960 | They're often described as an attempt to auto resuscitate.

00:54:34.540 | That is you take that super deep breath

00:54:37.620 | and that maybe it can kickstart the engine again.

00:54:40.880 | We do not know the degree to such things as gas

00:54:45.060 | are really sighs that are particularly large.

00:54:48.700 | And so if you suppress the ability to gasp

00:54:52.940 | in an individual who is subject to an overdose,

00:54:57.220 | then whereas they might been able

00:54:59.980 | to re-arouse their breathing,

00:55:03.100 | if that's prevented, they don't get re-aroused.

00:55:05.820 | So that is certainly a possibility.

00:55:08.980 | But this has not been investigated.

00:55:13.520 | I mean one of the things that I'm interested in

00:55:17.400 | is in individuals who have

00:55:20.640 | diseases which will affect pre-Butzinger complex.

00:55:26.640 | And there's data in Parkinson's disease

00:55:32.400 | and multiple system atrophy,

00:55:34.060 | which is another form of neurodegeneration

00:55:37.640 | where there's loss of neurons in pre-Butzinger.

00:55:40.400 | And the question is, and it also may happen in ALS,

00:55:47.580 | sometimes referred to as Lou Gehrig's disease,

00:55:50.160 | and mitral foot glottal sclerosis.

00:55:52.060 | These individuals often die during sleep.

00:55:57.860 | We have an idea that we have not been able

00:56:03.560 | to get anyone to test,

00:56:06.260 | is that patients with Parkinson's, patients with MLS,

00:56:11.260 | typically breathe normally during wakefulness.

00:56:16.480 | The disturbances that they have in breathing

00:56:19.240 | is during sleep.

00:56:20.080 | So Parkinson's patients at the end stages of the disease

00:56:24.380 | often have significant disturbances in their sleep pattern,

00:56:28.020 | but not during wakefulness.

00:56:30.040 | And we think that what could be happening

00:56:32.860 | is that the proximate cause of death is not heart failure,

00:56:37.260 | is that they become apneic,

00:56:39.020 | they stop breathing and don't resuscitate.

00:56:42.380 | And that resuscitation may or may not be due

00:56:46.820 | to an explicit suppression of size,

00:56:49.740 | but to an overall suppression of the whole apparatus

00:56:52.720 | of the pre-Butzinger complex.

00:56:54.800 | - Got it, thank you.

00:56:56.180 | So Yackel calls you up.

00:56:59.400 | - So he calls me up and he's great kids, super smart.

00:57:04.400 | And he tells me about these experiments that he's doing

00:57:10.000 | where he's looking at a database

00:57:14.240 | to try and find out what molecules are enriched

00:57:17.000 | in regions of the brain that are critical for breathing.

00:57:20.440 | So we and others have mapped out these regions

00:57:23.420 | in the brain stem.

00:57:25.200 | And he was looking at one of these databases

00:57:27.540 | to see what's enriched.

00:57:29.460 | And I said, that's great.

00:57:32.120 | We'd be willing to sort of share our work together.

00:57:34.560 | He says, no, my advisor doesn't want me to do that.

00:57:38.420 | So I said, okay, but Kevin's a great kid.

00:57:43.340 | And I enjoyed talking to him and he's a smart guy.

00:57:48.180 | And what I found in academia is that the smartest people

00:57:53.180 | only wanna hire people smarter than them

00:58:00.120 | and have the preference to interact

00:58:02.520 | with people smarter than them.

00:58:04.400 | The faculty who are not at the highest level

00:58:08.700 | and at every institution, there's a distribution.

00:58:12.400 | There are ones above the mean and those below the mean.

00:58:14.620 | Those who below the mean are very threatened by that.

00:58:17.760 | And I saw Kevin as like a shining light

00:58:23.660 | and I didn't care whether he was gonna out-compete me

00:58:26.720 | because whatever he did was gonna help me in the field.

00:58:29.820 | So I did whatever I can to help to work with Kevin.

00:58:34.020 | So at one point, I got invited to give grand rounds

00:58:37.880 | in neurology at Stanford.

00:58:40.160 | Turns out an undergraduate student who had worked with me

00:58:43.200 | was now head of the training program for neurologists

00:58:46.020 | at Stanford and he invited me.

00:58:49.040 | And at the end of my visit,

00:58:52.000 | I go to Mark Krausner's office and Kevin is there

00:58:56.400 | and a postdoc Pungley who was also working

00:58:59.560 | on a project was there.

00:59:01.920 | And towards the end of the conversation,

00:59:04.740 | Mark says to me, "You know, we found this one molecule

00:59:13.780 | "which is highly concentrated in an important region

00:59:18.100 | "for breathing."

00:59:19.140 | I said, "Oh, that's great, what is it?"

00:59:22.700 | And he says, "I can't tell you

00:59:24.140 | "because we wanna work on it."

00:59:25.780 | So of course I'm disappointed but I realized

00:59:31.460 | that the ethic in some areas of science

00:59:35.820 | or the custom in some areas of science

00:59:38.100 | is that until you get a publication,

00:59:40.100 | you'll be relatively restricted in sharing information.

00:59:42.820 | Mark and I are gonna have a chat when I get back.

00:59:45.520 | Well, he may remember the story differently

00:59:47.300 | but I said, "Okay."

00:59:49.760 | And as I'm walking out the door,

00:59:51.700 | I remember these experiments I described to you

00:59:54.720 | about bombastin and that was the only unusual molecule

00:59:57.920 | we're working in.

00:59:59.200 | So the reason I'm rushing out the door

01:00:01.480 | is I have a flight to catch.

01:00:03.280 | So I stick my head in and I said,

01:00:05.540 | "Is this molecule related to bombastin?"

01:00:09.580 | And then I run off, I don't even wait for them to reply.

01:00:12.140 | I get to the airport, Mark calls me and he says,

01:00:16.500 | "Bombastin, the peptide we found is related to bombastin,

01:00:20.120 | "what does it do?"

01:00:22.120 | And I said, "I'm not telling."

01:00:24.480 | (laughing)

01:00:26.160 | - Oh my.

01:00:27.480 | - I'm so glad I wasn't involved in this collaboration.

01:00:29.720 | - No, no, but that was sort of a tease

01:00:32.880 | 'cause I said, "Well, let's work together on this."

01:00:35.880 | And then we worked together on this.

01:00:36.720 | - It was a prisoner's dilemma at that point, yeah.

01:00:40.060 | So Kevin Yackel is spectacular, has his own lab at UCSF

01:00:46.380 | and the work that I'm familiar with from Kevin

01:00:50.360 | is worth mentioning now, or I'll ask you to mention it,

01:00:54.460 | which is this reciprocal relationship

01:00:57.120 | between brain state,

01:00:58.560 | where we could even say emotional state and breathing.

01:01:01.040 | And I'd love to get your thoughts

01:01:02.680 | on how breathing interacts with other things in the brain.

01:01:07.680 | You've beautifully described how breathing controls

01:01:09.800 | the lungs, the diaphragm and the interactions

01:01:11.640 | between oxygen and carbon dioxide and so forth.

01:01:14.660 | But as we know, when we get stressed, our breathing changes.

01:01:19.620 | When we're happy and relaxed, our breathing changes.

01:01:22.800 | But also if we change our breathing,

01:01:25.760 | we in some sense can adjust our internal state.

01:01:29.020 | What is the relationship between brain state and breathing?

01:01:33.240 | And if you would, because I know you have a particular love

01:01:37.780 | of one particular aspect of this,

01:01:41.440 | what is the relationship between brain rhythms,

01:01:44.680 | oscillations, if you will, and breathing?

01:01:47.480 | - This is a topic which has really intrigued me

01:01:50.840 | over the past decade.

01:01:52.600 | I would say before that, I was in my silo,

01:01:55.720 | just interested about how the rhythm of breathing

01:01:57.840 | is generated and didn't really pay much attention

01:02:00.640 | to this other stuff.

01:02:02.180 | For some reason, I got interested in it.

01:02:06.040 | And I think it was triggered by an article

01:02:08.120 | in the New York Times about mindfulness.

01:02:11.120 | Now, believe it or not, although I'd lived in California

01:02:14.080 | for 20 years at that time, I never heard of mindfulness.

01:02:17.480 | It's staggering how isolated you can be from the real world.

01:02:21.000 | And I Googled it, and there was a mindfulness institute

01:02:24.080 | at UCLA, and they were giving courses in meditation.

01:02:28.280 | So I said, oh, this is great, because I can now see

01:02:33.580 | whether or not the breathing part of meditation

01:02:36.880 | has anything to do with the purported effects of meditation.

01:02:40.280 | So I signed up for the course.

01:02:42.080 | And as I joked to you before, I had two goals.

01:02:45.880 | One was to see whether or not breathing had an effect,

01:02:49.600 | and the other was to levitate.

01:02:51.680 | Because I grew up with all these kung fu things,

01:02:54.480 | and all the monks could levitate when they meditated,

01:02:56.800 | so why not?

01:02:57.680 | We have a model in the lab.

01:03:01.320 | You can't do anything interesting

01:03:02.640 | if you're afraid of failing.

01:03:04.380 | And if I fail to levitate, well, at least I tried.

01:03:08.000 | And I should tell you now, I still haven't done it yet,

01:03:10.080 | but I haven't given up yet.

01:03:11.880 | I haven't given up.

01:03:12.840 | So I took this course in mindfulness,

01:03:17.160 | and it became apparent to me that the breathing part

01:03:22.160 | was actually critical.

01:03:24.120 | It wasn't simply a distraction or a focus.

01:03:27.720 | They could move your index finger to the same effect.

01:03:32.720 | But I really believed that the breathing part was involved.

01:03:36.560 | Now, I'm not an unbiased observer,

01:03:39.660 | so the question is, how can I demonstrate that?

01:03:44.560 | I didn't feel competent to do experiments in humans,

01:03:48.640 | and I didn't feel I could design

01:03:50.020 | the right experiments in humans,

01:03:51.280 | but I felt maybe I could study this in rodents.

01:03:55.340 | So we got this idea that we're gonna teach rodents

01:03:58.680 | to meditate, and that's laughable.

01:04:03.680 | But we said, but if we can,

01:04:08.280 | then we can actually study how this happens.

01:04:12.200 | So believe it or not,

01:04:14.840 | I was able to get a sort of a starter grant,

01:04:18.240 | an R21 from NCCIH.

01:04:21.240 | That's the National Complementary Medicine Institute.

01:04:25.960 | - A wonderful institute I should mention.

01:04:27.760 | Our government puts major tax dollars

01:04:31.000 | toward studies of things like meditation,

01:04:34.760 | breath work, supplements, herbs, acupuncture.

01:04:38.240 | This is, I think, not well known,

01:04:41.160 | and it's an incredible thing

01:04:42.920 | that our government does that,

01:04:46.000 | and I think it deserves a nod, and more funding.

01:04:49.480 | - I totally agree with you.

01:04:50.960 | I think that it's the kind of thing that many of us,

01:04:54.200 | including many scientists,

01:04:56.240 | thinks is too woo-woo and unsubstantiated.

01:04:59.760 | But we're learning more and more.

01:05:02.060 | We used to laugh at neuroimmunology,

01:05:03.920 | that the nervous system didn't have anything

01:05:05.440 | to do with the immune system.

01:05:07.040 | And pain itself can influence your immune system.

01:05:11.400 | I mean, there are all these things that we're learning

01:05:13.560 | that we used to dismiss,

01:05:15.320 | and I think there's real nuggets to be learned here.

01:05:19.880 | So they went out on a limb,

01:05:23.040 | and they funded this particular project.

01:05:25.720 | And now I'm gonna leap ahead,

01:05:27.120 | because for three years,

01:05:29.160 | we threw stuff up against the wall that didn't work.

01:05:32.500 | And recently, we had a major breakthrough.

01:05:37.500 | We found a protocol by which we can get mice

01:05:42.720 | to breathe slowly, awake mice to breathe slowly.

01:05:46.680 | I won't tell you.

01:05:48.480 | - Normally, they don't breathe slowly.

01:05:49.860 | - No, no.

01:05:50.700 | In other words, whatever their normal breath is,

01:05:52.140 | we could slow it down by a factor of 10,

01:05:55.220 | and they're fine doing that.

01:05:56.660 | So we could do that for,

01:05:59.220 | we did that 30 minutes a day

01:06:01.660 | for four weeks, okay?

01:06:04.360 | Like a breath practice.

01:06:05.720 | - Do they levitate?

01:06:06.720 | - We haven't measured that yet.

01:06:09.360 | I would say a priori,

01:06:12.440 | we haven't seen them floating to the top of their cage,

01:06:14.800 | but we haven't weighed them.

01:06:15.800 | Maybe they weigh less.

01:06:17.440 | You know, maybe, you know, levitation is graded.

01:06:21.680 | And so maybe if you weigh less,

01:06:23.280 | it's sort of a partial levitation.

01:06:25.280 | In any case,

01:06:26.120 | we then tested them.

01:06:30.800 | And we had control animals, mice,

01:06:34.560 | where we did everything the same,

01:06:37.120 | except the manipulation we made

01:06:39.600 | did not slow down their breathing.

01:06:41.960 | So, but they went through everything else.

01:06:44.100 | We then put them through a standard fear conditioning,

01:06:47.380 | which we did with my colleague, Michael Fanzolo,

01:06:49.920 | who's one of the real gurus of fear.

01:06:53.680 | And we measured a standard test

01:06:58.200 | is to put mice in a condition

01:07:01.740 | where they're concerned that we receive a shock,

01:07:05.260 | and their response is that they freeze.

01:07:07.840 | And the measure of how fearful they are

01:07:10.560 | is how long they freeze.

01:07:11.960 | This is well validated,

01:07:14.880 | and it's way above my pay grade to describe

01:07:17.880 | the validity of the test, but it's very valid.

01:07:21.600 | The control mice had a freezing time,

01:07:26.800 | which was just the same as ordinary mice would have.

01:07:30.640 | The ones that went through our protocol

01:07:32.440 | froze much, much less.

01:07:35.120 | According to Michael,

01:07:38.200 | the degree to which they showed less freezing

01:07:42.960 | was as much as if there was a major manipulation

01:07:46.180 | in the amygdala, which is a part of the brain

01:07:48.600 | that's important in fear processing.

01:07:51.040 | It's a staggering change.

01:07:53.360 | The problem we have now is the grant ran out of money,

01:07:56.960 | the postdoc working on it left,

01:07:59.160 | and now we have to try and piece together everything.

01:08:02.160 | But the data is spectacular.

01:08:06.040 | - Well, I think I'll just pause you for a moment there,

01:08:08.500 | because I think that you're talking about a rodent study,

01:08:11.180 | but I think the benefits of doing rodent studies

01:08:14.120 | that you can get deep into mechanism,

01:08:16.740 | and for people that might think,

01:08:20.440 | well, we've known that meditation has these benefits,

01:08:22.760 | why do you need to get mechanistic science?

01:08:24.660 | I think that one thing that's important

01:08:27.160 | for people to remember is that, first of all,

01:08:30.080 | as many people as one might think are meditating out there

01:08:33.720 | or doing breath work,

01:08:35.440 | a far, far, far greater number of people are not, right?

01:08:38.920 | I mean, the majority of people don't take any time

01:08:42.320 | to do dedicated breath work nor meditate.

01:08:46.320 | So whatever can incentivize people would be wonderful.

01:08:50.620 | But the other thing is that it's never really been clear

01:08:53.360 | to me just how much meditation is required

01:08:56.260 | for a real effect, meaning a practical effect.

01:08:59.700 | People say 30 minutes a day, 20 minutes a day,

01:09:01.840 | once a week, twice a week, same thing with breath work.

01:09:04.780 | Finding minimum or effective thresholds

01:09:07.620 | for changing neural circuitry

01:09:09.820 | is what I think is the holy grail of all these practices.

01:09:13.740 | And that's only going to be determined

01:09:15.140 | by the sorts of mechanistic studies that you describe.

01:09:17.380 | So this is wonderful.

01:09:18.480 | I do hope the work gets completed,

01:09:20.340 | and we can talk about ways that we can ensure

01:09:23.500 | that that happens, but-

01:09:25.280 | - But let me add one thing to what you're saying, Andrew.

01:09:28.320 | One of the issues I think for a lot of people

01:09:31.720 | is that there's a placebo effect.

01:09:34.400 | That is, in humans, they can respond to something

01:09:38.140 | even though the mechanism has nothing to do

01:09:40.440 | with what the intervention is.

01:09:43.440 | And so it's easy to say that the meditative response

01:09:48.520 | has a big component, which is the placebo effect.

01:09:51.640 | My mice don't believe in the placebo effect.

01:09:54.420 | And so if we could show there's a bona fide effect in mice,

01:09:58.240 | it is convincing in ways that no matter

01:10:01.160 | how many human experiments you did,

01:10:03.220 | the control for the placebo effect

01:10:04.720 | is extremely difficult in humans.

01:10:06.880 | In mice, it's a non-issue.

01:10:09.580 | So I think that that in and of itself

01:10:12.060 | would be an enormous message to send.

01:10:14.480 | - Excellent, and indeed a better point.

01:10:18.460 | I think a 30-minute-a-day meditation in these mice,

01:10:22.620 | if I understand correctly, the meditation,

01:10:27.100 | we don't know what they're thinking about.

01:10:27.940 | - Well, it's breath practice really.

01:10:28.780 | - Right, so it's breath practice.

01:10:30.200 | So because we don't, presumably they're not thinking

01:10:32.660 | about their third eye center, lotus position, levitation,

01:10:35.280 | whatever it is, they're not instructed as to what to do.

01:10:38.120 | And if they were, they probably wouldn't do it anyway.

01:10:40.440 | So 30 minutes a day in which breathing is deliberately slowed

01:10:44.460 | or is slowed relative to their normal patterns of breathing.

01:10:48.100 | Got it.

01:10:48.940 | What was the frequency of sighing during that 30 minutes?

01:10:54.340 | Unclear? - We don't know yet.

01:10:55.320 | Well, no, we have the data.

01:10:56.560 | We just, we're analyzing the data.

01:10:58.420 | - To be determined or to be announced at some point.

01:11:01.220 | So the fear centers are altered in some way

01:11:06.220 | that creates a shorter fear response to a foot shock.

01:11:10.880 | - Right.

01:11:12.500 | What are some other examples that you are aware of

01:11:14.700 | from work in your laboratory or work in other laboratories

01:11:17.280 | for that matter about interactions between breathing

01:11:20.140 | and brain state or emotional state?

01:11:22.420 | - So this gets back to our prior conversation.

01:11:25.380 | I sort of went off on that tangent.

01:11:27.180 | We need, I think we need to think separately

01:11:33.540 | of the effect of volitional changes of breathing

01:11:37.860 | on emotion versus the effect of brain state on breathing.

01:11:42.860 | So the effect of brain state on breathing,

01:11:49.700 | like when you're stressed is an effect

01:11:54.260 | or presumably originating in higher centers,

01:11:57.460 | if I can use that term, affecting breathing.

01:12:00.160 | It's the reciprocal is that when you change breathing,

01:12:05.680 | it affects your emotional state.

01:12:07.700 | I think of those two things as different

01:12:11.180 | than they ultimately be tied together.

01:12:13.100 | So there's a landmark paper published in the '50s

01:12:16.540 | where they stimulated in the amygdala of cats.

01:12:20.500 | And depending on where they stimulated,

01:12:22.460 | they got profound changes in breathing.

01:12:25.340 | There's like every pattern of breathing

01:12:26.860 | could possibly imagine they found a site in the amygdala

01:12:29.500 | which could produce that.

01:12:31.300 | So there's clearly a powerful descending effect

01:12:34.420 | coming from the amygdala, which is a major site

01:12:38.140 | for processing emotion, fear, stress, and whatnot

01:12:41.140 | that can affect breathing.

01:12:43.180 | And clearly we have volitional control over breathing.

01:12:45.820 | So we have profound effects there.

01:12:48.700 | Now I should say about emotional control of breathing,

01:12:51.100 | I need to segue into talking about locked-in syndrome.

01:12:55.280 | Locked-in syndrome is a devastating lesion

01:13:00.260 | that happens in a part of the brainstem

01:13:02.980 | where signals that controlled muscles are transmitted.

01:13:07.980 | So the fibers coming from your motor cortex

01:13:12.620 | go down through this part of the brainstem,

01:13:16.580 | which is called the ventral pons.

01:13:19.260 | And if there's a stroke there,

01:13:21.900 | it can damage these pathways.

01:13:25.180 | What happens in individuals who have locked-in syndrome

01:13:28.100 | is they lose all volitional movement

01:13:30.860 | except lateral movement of the eyes

01:13:33.380 | and maybe the ability to blink.

01:13:35.460 | The reason they're able to still blink and move their eyes

01:13:39.700 | is that those control centers are rostral,

01:13:44.700 | closer to, are not interrupted.

01:13:47.580 | In other words, the interruption is below that.

01:13:50.480 | They continue to breathe because the centers for breathing

01:13:55.780 | don't require that volitional command.

01:13:58.380 | In any case, they're below that.

01:14:00.060 | So they're fine.

01:14:01.380 | So these people continue to breathe.

01:14:03.500 | Normal intelligence, but they can't move.

01:14:08.500 | There's a great book called

01:14:10.060 | "The Diving Bell and the Butterfly"

01:14:11.540 | about a young man who this happens to

01:14:16.540 | and he describes his life.

01:14:19.980 | And it's a real testament to the human condition

01:14:23.860 | that he does this.

01:14:25.220 | It's a remarkable book.

01:14:26.340 | It's a short book.

01:14:27.440 | - Did he write the book by blinking two translators?

01:14:29.860 | - He did it by blinking to his caretaker.

01:14:32.580 | It's pretty amazing.

01:14:34.460 | And there was a movie which I've never seen

01:14:37.180 | with Javier Bardin as the protagonist,

01:14:40.760 | but the book I highly recommend to anyone to read.

01:14:44.480 | So I had colleagues studying an individual

01:14:47.420 | who had locked in syndrome.

01:14:48.720 | And this patient breathed very robotically,

01:14:53.660 | totally consistent, very regular.

01:14:57.620 | They gave the patient a low oxygen mixture to breathe.

01:15:01.340 | Ventilation went up.

01:15:03.060 | A CO2 mixture to breathe, ventilation went up.

01:15:05.620 | So all the regulatory apparatus for breathing was there.

01:15:08.420 | They asked the patient to hold his breath

01:15:11.540 | or to breathe faster.

01:15:13.340 | Nothing happened.

01:15:15.000 | Just the patient recognized the command,

01:15:18.040 | but couldn't change it.

01:15:19.060 | Then all of a sudden the patient's breathing

01:15:20.820 | changed considerably.

01:15:22.740 | And they said to the patient, "What happened?"

01:15:24.220 | They said, "You told a joke and I laughed."

01:15:27.980 | And they went back.

01:15:29.940 | Whenever they told a joke that the patient found funny,

01:15:33.220 | the patient's breathing pattern changed.

01:15:35.540 | And you know your breathing pattern when you laugh is,

01:15:39.740 | you know, you inhale, you go ha ha ha ha.

01:15:42.300 | But it's also very distinctive.

01:15:43.940 | We have some neuroscience colleagues who will go unnamed,

01:15:47.220 | who if you heard them laugh 50 yards away,

01:15:50.340 | you know exactly who they are.

01:15:51.720 | - Yeah, well, I'll name them.

01:15:53.620 | Eric Kandel has an inspiratory laugh.

01:15:56.900 | - He's famous for a, as opposed to a ha ha.

01:16:00.020 | - Exactly, exactly.

01:16:01.580 | So it's very stereotyped,

01:16:04.860 | but it's maintained and these people

01:16:07.780 | lose volitional control of breathing.

01:16:10.180 | So there's an emotive component controlling your breathing,

01:16:13.700 | which has nothing to do with your volitional control.

01:16:17.780 | And it goes down to a different pathway

01:16:19.780 | 'cause it's not disrupted by this lockdown syndrome.

01:16:23.820 | If you look at motor control of the face,

01:16:27.380 | we have the volitional control of the face,

01:16:29.180 | but we also have emotional control of the face,

01:16:32.780 | which most of us can't control.

01:16:36.180 | So when we look at another person,

01:16:38.340 | we tend, we're able to read a lot

01:16:41.220 | about what their emotional state is.

01:16:43.820 | And that's a lot about how primates communicate,

01:16:46.500 | humans communicate.

01:16:48.000 | And you have people who are good deceivers,

01:16:51.260 | probably used car salesman, poker players,

01:16:55.700 | or now poker players have tells,

01:16:58.440 | but many of them now wear dark glasses

01:17:01.320 | because a lot of the tells you blink or whatnot.

01:17:03.640 | - Pupil size is a tell.

01:17:04.480 | - Pupil size, pupil size is a tell,

01:17:07.580 | which is an autonomic function,

01:17:09.700 | not a skeletal muscle function.

01:17:13.500 | But we have all these skeletal muscles

01:17:15.580 | which we're controlling, which give us away.

01:17:20.180 | I've tried to get my imaging friends

01:17:23.260 | to image some of the great actors

01:17:25.100 | that we have in Los Angeles.

01:17:27.540 | - You mean brain imagers?

01:17:28.620 | - Brain imagers, I'm sorry.

01:17:29.820 | - No, that's all right.

01:17:30.660 | - I mean, yeah, brain imagers.

01:17:32.340 | Because I think when I asked you to smile,

01:17:37.340 | I could tell that you're not happy,

01:17:41.700 | that you're smiling because I asked you to smile.

01:17:43.700 | - I think you're about to crack a joke,

01:17:45.540 | but we're old friends, so.

01:17:48.060 | - No, I'm not, that when you see a picture

01:17:53.060 | like at a birthday or whatnot and say cheese,

01:17:56.660 | you could tell that at least half of the people

01:17:58.700 | are not happy they're saying cheese.

01:18:01.180 | Whereas a great actor, when they're able to dissemble

01:18:06.180 | in the fact that they're sad or they're happy,

01:18:08.960 | you believe it, they're not faking it.

01:18:10.660 | It's like that's great acting.

01:18:13.020 | And I don't think everyone could do that.

01:18:15.040 | I think that the individuals who are able to do that

01:18:18.120 | have some connection to the parts

01:18:21.820 | of their emotive control system

01:18:23.380 | that the rest of us don't have.

01:18:25.040 | Maybe they develop it through training and maybe not,

01:18:27.920 | but I think that this can be imaged.

01:18:29.480 | So I would like to get one of these great actors

01:18:33.000 | in a imager and have them go through that

01:18:36.000 | and then get a normal person

01:18:38.280 | and see whether or not they can emulate that.

01:18:40.420 | And I think you're gonna find big differences

01:18:42.760 | in the way they control this emotive thing.

01:18:44.880 | So this emotive control of the facial muscles,

01:18:48.360 | I think is in large part similar

01:18:50.600 | to the emotive control of breathing.

01:18:52.440 | So there's that emotive control

01:18:54.840 | and there's that volitional control and they're different.

01:18:58.240 | They're different.

01:18:59.360 | Now, you asked me about the Yakko stuff.

01:19:03.760 | The Yakko paper had to do with ascending,

01:19:07.680 | that the effect of breathing on emotion.

01:19:10.460 | What Kevin found was that there was a population

01:19:14.480 | of neurons in the pre-Butsinger complex

01:19:18.400 | that were always looking to things

01:19:21.280 | that are projecting ultimately emotive neurons.

01:19:23.400 | He found the population of cells

01:19:25.060 | that projected to locus coeruleus.

01:19:27.960 | Locus coeruleus, excuse me,

01:19:29.840 | is one of those places in the brain

01:19:32.300 | that seemed to go everywhere.

01:19:34.360 | - It's like a sprinkler system.

01:19:35.680 | - Exactly, exactly.

01:19:37.560 | And influence mood and you've had podcasts about this.

01:19:41.800 | I mean, there's a lot of stuff going on with the amygdala.

01:19:44.220 | So, I'm sending the locus coeruleus.

01:19:46.600 | So you get into the locus coeruleus,

01:19:48.940 | you can now spray information out

01:19:50.720 | throughout the entire brain.

01:19:52.160 | He found specific cells that projected

01:19:56.440 | from pre-Butsinger to locus coeruleus.

01:19:59.480 | And that these cells are inspiratory modulator.

01:20:03.520 | Now, it's been known for a long time, since the '60s,

01:20:09.920 | that if you look in the locus coeruleus of cats

01:20:13.620 | when they're awake, you find many neurons

01:20:16.080 | that have respiratory modulation.

01:20:17.800 | No one paid much attention to them.

01:20:20.600 | Why bother?

01:20:22.520 | Not why bother paying attention,

01:20:23.940 | but why would the brain bother to have these inputs?

01:20:26.880 | So what Kevin did with Lindsey Schwartz

01:20:30.920 | and Leshun Lozliya, is they killed, or bladed,

01:20:35.920 | those cells going to locus coeruleus from pre-Butsinger.

01:20:41.320 | And the animals became calmer.

01:20:43.760 | And their EEG levels changed in ways

01:20:47.680 | that are indicative that they became calmer.

01:20:49.900 | - And as I recall, they didn't just become calmer,

01:20:51.820 | but they weren't really capable of high arousal states.

01:20:55.520 | They were kind of flat.

01:20:56.980 | - I don't think we really pursued that in the paper.

01:21:01.800 | And so we'd have to ask Johnny Huguenin about that, but I-

01:21:08.120 | - He's on the other side of my lap, so we'll ask him.

01:21:11.280 | - But nonetheless, that beautifully illustrates

01:21:16.280 | how there is a bi-directional control, right?

01:21:21.600 | - Well, that's a-

01:21:22.440 | - Emotion, well, no, the two stories

01:21:26.800 | of the locked-in syndrome, plus the Yakl paper,

01:21:30.720 | shows that emotional states influence breathing,

01:21:33.480 | and breathing influences emotional states.

01:21:35.580 | But you mentioned inspiration,

01:21:38.900 | which I always call inhalation,

01:21:40.120 | but people will follow, no, no, it's fine.

01:21:42.660 | Those are interchangeable, people can follow that.

01:21:45.160 | There's some interesting papers from Noam Sobel's group

01:21:48.680 | and from a number of other groups that as we inhale,

01:21:51.360 | or right after we inhale,

01:21:53.400 | the brain is actually more alert and capable

01:21:55.560 | of storing information than during exhales,

01:21:58.480 | which I find incredible, but it also makes sense.

01:22:01.640 | I'm able to see things far better when my eyes are open

01:22:04.360 | than when my eyelids are closed for that matter.

01:22:06.800 | - Maybe.

01:22:10.100 | - I don't doubt, Noam's work is great.

01:22:13.400 | Let me backtrack a bit, because I want people to understand

01:22:19.840 | that when we're talking about breathing

01:22:21.560 | affecting emotional cognitive state,

01:22:24.440 | it's not simply coming from pre-Butzinger.

01:22:27.740 | There are at least, well, there are several other sites,

01:22:33.080 | and let me sort of, I need to sort of go through that.

01:22:35.940 | One is olfaction.

01:22:38.020 | So when you're breathing, normal breathing,

01:22:41.520 | you're inhaling and exhaling.

01:22:44.040 | This is creating signals coming from the nasal mucosa

01:22:48.200 | that is going back into the olfactory bulb

01:22:51.760 | that's respiratory modulated.

01:22:53.920 | And the olfactory bulb has a profound influence

01:22:57.620 | and projections through many parts of the brain.

01:23:00.900 | So there's a signal arising from this rhythmic moving of air

01:23:05.700 | in and out of the nose that's going into the brain

01:23:08.760 | that has contained in it a respiratory modulation.

01:23:12.400 | So that signal is there.

01:23:14.040 | The brain doesn't have to be using it,

01:23:15.720 | but when it's discriminating over and whatnot,

01:23:18.760 | that's riding on a oscillation which is respiratory related.

01:23:22.860 | Another potential source is the vagus nerve.

01:23:27.240 | The vagus nerve is a major nerve

01:23:29.640 | which is containing afferents from all of the viscera.

01:23:34.480 | - Afferents just being signals too.

01:23:37.540 | - Signals from the viscera.

01:23:39.120 | It also has signals coming from the brain stem down

01:23:42.340 | which are called efferents,

01:23:43.920 | but it's getting major signals from the lung, from the gut,

01:23:48.260 | and this is going up into the brain stem.

01:23:51.740 | So it's there.

01:23:52.980 | There are very powerful receptors in the lung

01:23:58.060 | that are responding to the lung volume, the lung stretch.

01:24:02.260 | - Is there barrier receptors?

01:24:04.040 | - I'm sorry, we have a number like the piezo receptors

01:24:08.480 | of this year's Nobel Prize, yeah.

01:24:11.120 | - So they're responding to the expansion

01:24:14.960 | and relaxation in the lung.

01:24:16.920 | And so if you record from the vagus nerve,

01:24:19.060 | you'll see that there's a huge respiratory modulation

01:24:22.800 | due to the mechanical changes in the lung.

01:24:25.040 | Now, why that is of interest is that

01:24:28.560 | for some forms of refractory depression,

01:24:33.800 | electoral stimulation of the vagus nerve

01:24:36.640 | can provide tremendous relief.

01:24:38.720 | Why this is the case still remains to be determined,

01:24:42.600 | but it's clear that signals in the vagus nerve,

01:24:46.120 | at least artificial signals in the vagus nerve,

01:24:48.800 | can have a positive effect on reducing depression.

01:24:52.700 | So it's not a leap to think that under normal circumstances

01:24:57.200 | that that rhythm coming in from the vagus nerve

01:25:00.440 | is playing a role in normal processing.

01:25:04.260 | Okay, let me continue.

01:25:07.040 | Carbon dioxide and oxygen levels.

01:25:09.300 | Now, under normal circumstances,

01:25:11.580 | your oxygen levels are fine.

01:25:14.600 | And unless you go to altitude,

01:25:16.800 | they don't really change very much.

01:25:19.120 | But your CO2 levels can change quite a bit

01:25:22.280 | with even a relatively small change

01:25:24.240 | in your overall breathing.

01:25:25.920 | That's gonna change your pH level.

01:25:29.160 | I have a colleague, Alicia Marrette,

01:25:32.400 | who is working with patients who are anxious,

01:25:37.360 | and many of them hyperventilate.

01:25:40.780 | And as a result of that hyperventilation,

01:25:43.560 | their carbon dioxide levels are low.

01:25:45.460 | And she has developed a therapeutic treatment

01:25:51.620 | where she trains these people to breathe slower

01:25:57.600 | and to restore their CO2 levels back to normal,

01:26:01.160 | and she gets relief from their anxiety.

01:26:04.160 | So CO2 levels, which are not gonna affect brain function

01:26:09.800 | on a breath by breath level,

01:26:11.640 | although it does fluctuate breath by breath,

01:26:14.820 | but sort of as a continuous background, can change.

01:26:19.040 | And if it's changed chronically,

01:26:21.120 | we know that highly elevated levels of CO2

01:26:24.760 | can produce panic attacks.

01:26:27.820 | And we don't know the degree to that gets exacerbated

01:26:32.820 | by people who have a panic attack

01:26:36.380 | to the degree to which their ambient CO2 levels

01:26:39.020 | are affecting their degree of discomfort.

01:26:42.860 | - What about people who tend to be too calm,

01:26:46.420 | meaning that they're feeling sleepy,

01:26:48.420 | they're underbreathing as opposed to overbreathing?

01:26:53.000 | Is there any knowledge of what the status of CO2 is

01:26:56.460 | in their system?

01:26:57.440 | - I don't know, which doesn't mean there's no knowledge,

01:27:00.000 | but I'm unaware, but that's blissfully unaware.

01:27:04.660 | I have not looked at that literature, so I don't know.

01:27:07.420 | - And I have a feeling, I mean, most people,

01:27:09.760 | or excuse me, most of the scientific literature

01:27:11.620 | around breathing in humans that I'm aware of

01:27:13.980 | relates to these stressed states

01:27:15.380 | because they're a little bit easier to study in the lab,

01:27:17.300 | whereas people feeling understimulated

01:27:19.840 | or exhausted all the time,

01:27:21.120 | it's a complicated thing to measure.

01:27:23.420 | I mean, you can do it, but it's not as straightforward.

01:27:25.100 | - Well, CO2 is easy to measure.

01:27:27.020 | - But in terms of the sort of the measures

01:27:29.380 | for feeling fatigued, they're somewhat indirect.

01:27:33.420 | Whereas stress, we can get at pulse rates

01:27:35.900 | and HRV and things of that sort.

01:27:37.220 | - Well, I imagine that these devices that we're all wearing

01:27:41.180 | will soon be able to measure,

01:27:42.580 | well, now they can measure oxygen levels, oxygen saturation.

01:27:45.780 | - Which is amazing.

01:27:46.820 | - Yeah, but oxins will pretty much stay above 90%

01:27:52.860 | unless there's some pathology or you go to altitude.

01:27:57.500 | But CO2 levels vary quite a bit.

01:28:00.500 | And CO2, in fact, because they vary,

01:28:03.380 | your body is so sensitive, the control of breathing,

01:28:06.820 | like how much you breathe per minute,

01:28:09.140 | is determined in a very sensitive way by the CO2 level.

01:28:14.060 | So even a small change in your CO2

01:28:17.180 | will have a significant effect on your ventilation.

01:28:20.380 | So this is another thing that not only changes

01:28:23.300 | your ventilation, but affects your brain state.

01:28:26.500 | Now, another thing that could affect breathing,

01:28:30.100 | how breathing practice can affect your emotional state

01:28:32.780 | is simply the descending command.

01:28:36.340 | Because breathing practice involves volitional control

01:28:39.340 | of your breathing, and therefore there's a signal

01:28:43.060 | that's originating somewhere in your motor cortex.

01:28:46.160 | That is not, of course, that's gonna go down

01:28:48.580 | to pre-Butzinger, but it's also gonna send off collaterals

01:28:52.420 | to other places.

01:28:53.660 | Those collaterals could obviously influence

01:28:55.660 | your emotional state.

01:28:56.740 | So we have quite a few different potential sources.

01:29:01.700 | None of them are exclusive.

01:29:03.380 | There's an interesting paper which shows that

01:29:07.180 | if you block nasal breathing,

01:29:11.940 | you still see breathing-related oscillations in the brain.

01:29:16.060 | And this is where I think the mechanism is occurring

01:29:21.060 | is that these breathing-related oscillations in the brain,

01:29:25.380 | they are playing a role in signal processing.

01:29:28.800 | And maybe, should I talk a little bit about the role

01:29:31.520 | that oscillations may be playing in signal processing?

01:29:34.180 | - Definitely, but before you do,

01:29:35.820 | I just want to ask you a intermediate question.

01:29:39.900 | We've talked a lot about inhalation,

01:29:41.540 | inspiration, and exhalation.

01:29:44.540 | What about breath holds?

01:29:46.440 | You know, in apnea, for instance,

01:29:48.780 | people are holding their breath,

01:29:50.100 | whether or not it's conscious or unconscious,

01:29:53.780 | they're holding their breath.

01:29:55.340 | What's known about breath holds

01:29:57.660 | in terms of how it might interact with brain state

01:29:59.940 | or oxygen CO2?

01:30:01.860 | And I'm particularly interested in how

01:30:03.980 | breath holds with lungs empty

01:30:05.420 | versus breath holds with lungs full

01:30:07.820 | might differ in terms of their impact on the brain.

01:30:10.240 | I'm not aware of any studies on this.

01:30:13.360 | Looking at a mechanistic level,

01:30:14.960 | but I find it really interesting.

01:30:16.480 | And even if there are no studies,

01:30:18.820 | I'd love it if you'd care to speculate.

01:30:20.680 | - Well, one of the breath practices that intrigued me

01:30:23.460 | is where you basically hyperventilate for a minute

01:30:27.460 | and then hold your breath for as long as you can.

01:30:29.460 | - Tummo style, Wimlof style, or we call it in the laboratory

01:30:33.720 | because frankly, before Tummo and before Wim,

01:30:36.940 | it was referred to as cyclic hyperventilation.

01:30:42.980 | So it's basically, right, followed by a breath hold.

01:30:46.400 | And that breath hold could be done with lungs full

01:30:47.900 | or lungs empty.

01:30:49.180 | - So I had a long talk with some colleagues

01:30:52.940 | about what they might think the underlying mechanisms are,

01:30:57.480 | particularly for the breath hold.

01:30:59.720 | And I certainly envisioned that there's a component

01:31:04.720 | with respect to the presence or absence of that rhythmicity

01:31:10.060 | in your cortex, which is having effect.

01:31:12.560 | But the other thing with the hyperventilation,

01:31:15.340 | hypoventilation, or the apnea,

01:31:17.480 | is your CO2 levels are going from low to high.

01:31:23.360 | - Anytime you're holding your breath.

01:31:24.740 | - Anytime you're holding your breath, okay?

01:31:26.880 | And those are gonna have a profound influence.

01:31:29.560 | Now, I have to talk about episodic hypoxia

01:31:34.480 | 'cause there's a lot of work going on,

01:31:38.020 | particularly with Gordon Mitchell,

01:31:39.380 | at the University of Florida, is doing some extraordinary work

01:31:42.580 | on episodic hypoxia.

01:31:44.820 | So in the '80s, David Millhorn

01:31:47.480 | did some really intriguing work.

01:31:50.780 | If I ask you to hold your breath, excuse me,

01:31:55.700 | if I gave you a low oxygen mixture for a couple of minutes,

01:32:00.700 | your breathing level would go up

01:32:03.340 | 'cause you wanna have more oxygen.

01:32:05.660 | - You're starving for air.

01:32:06.480 | - Yeah, no, you're starving for oxygen.

01:32:07.980 | - Right. - Okay.

01:32:09.440 | And for a couple of minutes, you'd go up,

01:32:13.620 | you'd reach some steady state level.

01:32:16.320 | Not so hypoxic that you can't reach an equilibrium.

01:32:19.700 | And then I give you a room air again,

01:32:21.960 | your ventilation quickly relaxes back down to normal.

01:32:24.720 | If on the other hand, I gave you three minutes of hypoxia,

01:32:31.020 | five minutes of normoxia,

01:32:33.220 | three minutes of hypoxia, five minutes of normoxia,

01:32:36.140 | three minutes of hypoxia, five minutes of normoxia.

01:32:38.180 | - Normoxia being normal. - Normal air.

01:32:40.500 | Your ventilation goes up, down, up, down, up, down, up, down.

01:32:45.160 | After the last episode, your breathing comes down

01:32:49.420 | and doesn't continue to come down,

01:32:50.820 | but rises again and stays up for hours, okay?

01:32:55.420 | This is well validated now.

01:32:58.740 | This was originally done in animals,

01:33:00.220 | but in humans all the time.

01:33:01.660 | It seems to have profound benefit

01:33:04.580 | on motor function and cognitive function.

01:33:08.240 | - In what direction?

01:33:09.340 | - Positive, positive.

01:33:11.660 | I've often toyed with the idea of getting a 5%,

01:33:14.260 | an 8% oxygen, don't do this listeners,

01:33:17.380 | getting an 8% oxygen tank by my desk

01:33:21.220 | when I'm writing a grant and doing like in Blue Velvet

01:33:24.420 | and going through the episodic hypoxia

01:33:28.220 | to improve my cognitive function.

01:33:30.380 | 'Cause certainly could use improvement

01:33:31.780 | when I'm writing grants.

01:33:32.780 | - But you could do this without the low oxygen.

01:33:35.940 | I mean, you could do this through breath work, presumably.

01:33:38.100 | - It's hard to lower your oxygen enough, okay?

01:33:42.380 | We're going in the experimental studies,

01:33:44.620 | they typically use 8% oxygen.

01:33:47.140 | It's hard to hold your breath long enough.

01:33:49.240 | And there is another difference here.

01:33:53.240 | That is what's happening to your CO2 levels.

01:33:56.380 | When you hold your breath,

01:33:58.220 | your oxygen levels are dropping,

01:33:59.380 | your CO2 levels are going up.

01:34:01.660 | When you're doing episodic hypoxia,

01:34:06.340 | your CO2 levels are going to stay pretty normal.

01:34:10.180 | 'Cause you're still breathing,

01:34:12.300 | it's just the oxygen levels are gone.

01:34:13.820 | - So unlike normal conditions, which you described before,

01:34:16.580 | where oxygen is relatively constant and CO2 is fluctuating

01:34:21.220 | depending on emotional state and activity

01:34:23.400 | and things of that sort.

01:34:24.420 | In episodic hypoxia, CO2 is relatively constant,

01:34:29.060 | but you're varying the oxygen level

01:34:30.700 | coming into the system quite a bit.

01:34:32.340 | - I would say it's relatively,

01:34:33.620 | I would say CO2 is relatively constant,

01:34:36.940 | but it's not going to go in a direction

01:34:40.380 | which is going to be significantly far from normal.

01:34:43.780 | Whereas when you're holding your breath,

01:34:45.780 | you're going to become both hypoxic

01:34:47.460 | and hypercapnic at the same time.

01:34:49.580 | - We should explain to people

01:34:50.500 | what hypoxic and hypercapnic are,

01:34:52.160 | because we haven't done that.

01:34:53.000 | - Hypoxic is just the technical term

01:34:54.060 | for low levels of oxygen.

01:34:55.980 | Hyper, or you could say hypoxic, low.

01:34:59.020 | Hyper is high, so hyperoxia, or hypocapnia, low CO2,

01:35:03.940 | or hypercapnia, high levels of CO2.

01:35:06.740 | So when you're in episodic hypoxia,

01:35:13.940 | if anything, you're going to become hypocapnic,

01:35:16.620 | not hypercapnic, and that could play an influence on this.

01:35:20.880 | One example that I remember,

01:35:23.900 | and Gordon will have to forgive me if I'm misquoting this,

01:35:27.180 | is they had a patient who had a stroke

01:35:32.180 | and had weakness in ankle flexion.

01:35:36.220 | That is, excuse me, ankle extension to extend the ankle.

01:35:41.220 | And so they had the patient in a seat

01:35:44.300 | where they could measure ankle extension,

01:35:46.940 | and then they measured it,

01:35:49.300 | and then they exposed the patient to episodic hypoxia,

01:35:53.420 | and they measured again the strength of the ankle extension

01:35:57.500 | went way up.

01:35:59.100 | And so Gordon is looking at this.

01:36:01.100 | They're looking at this now for spinal cord rehab.

01:36:04.260 | - And I imagine for all sorts of neuromuscular performance,

01:36:08.140 | it could be beneficial.

01:36:09.860 | - Gordon is looking into athletic performance.

01:36:12.820 | We have a project which we haven't been able

01:36:14.900 | to push to the next level to do golf.

01:36:18.740 | So I think- - Why golf?

01:36:20.580 | 'Cause you love golf.

01:36:21.820 | - Well, it's because it's motor performance, coordination,

01:36:26.100 | so it's not simply running as fast as you can.

01:36:29.100 | It's coordination, it's concentration,

01:36:31.100 | it's a whole variety of things.

01:36:33.060 | And so the idea would be to get a group of golfers

01:36:36.500 | and give them their placebo control

01:36:39.420 | so they don't know whether they're breathing a gas mixture

01:36:41.860 | which is just normal air or hypoxic gas mixture,

01:36:45.600 | although they may be able to figure it out

01:36:47.140 | based on their response.

01:36:48.440 | Do it under controlled circumstances

01:36:51.580 | or do it into a net.

01:36:53.340 | Measure their length of their drives,

01:36:55.540 | their dispersion and whatnot, and see what happens.

01:36:58.620 | Look, if we could find that this works for golfers,

01:37:03.160 | forget about cognitive function.

01:37:05.460 | We could sell this for unbelievable amounts of money.

01:37:09.460 | - That sounds like a terrible idea.

01:37:11.260 | - By the way, I'm not serious about selling it.

01:37:16.140 | - I know you're joking.

01:37:17.220 | Maybe people should know that you are joking about that.

01:37:19.300 | - No, I think that anything that can improve

01:37:21.860 | cognitive and neuromuscular performance

01:37:23.500 | is gonna be of interest for a wide range

01:37:25.860 | of both pathologic states like injury, TBI, et cetera.

01:37:30.220 | I mean, one of the most frequent questions I get

01:37:33.200 | is about recovery from concussion or traumatic brain injury.

01:37:37.180 | A lot of people think sports, they think football,

01:37:39.220 | they think rugby, they think hockey.

01:37:41.020 | But if you look at the statistics on traumatic brain injury,

01:37:44.540 | most of it is construction workers,

01:37:46.820 | car crashes, bicycle accidents.

01:37:48.820 | I mean, the sports part of it is a tiny, tiny

01:37:52.740 | minuscule fraction of the total amount

01:37:54.620 | of traumatic brain injury out there.

01:37:56.420 | I think these protocols tested in the context of golf

01:37:59.900 | would be very interesting because of the constraints

01:38:02.300 | of the measures, as you mentioned,

01:38:03.700 | and it could be exported to a number of things.

01:38:05.860 | I wanna just try and imagine whether or not

01:38:08.940 | there is any kind of breathing pattern or breath work,

01:38:13.940 | just to be direct about it,

01:38:15.780 | that even partially mimics what you described

01:38:19.500 | in terms of episodic hypoxia.

01:38:21.540 | I've done a lot of tumor Wim Hof cyclic hyperventilation

01:38:24.260 | type breathing before.

01:38:25.140 | My lab studies this in humans.

01:38:26.620 | And what we find is that if people do

01:38:29.860 | cyclic hyperventilation, so for about a minute,

01:38:32.380 | then exhale, hold their breath for 15 to 60 seconds,

01:38:35.280 | depending on what they can do,

01:38:36.300 | and just keep repeating that for about five minutes,

01:38:39.000 | it seems to me that it at least partially mimics

01:38:42.380 | the state that you're talking about.

01:38:43.620 | Because afterwards people report heightened levels

01:38:46.660 | of alertness, lower levels of kind of triggering

01:38:51.660 | due to stressful events.

01:38:54.540 | They feel comfortable at a higher level

01:38:56.060 | of autonomic arousal, cognitive focus,

01:38:58.500 | a number of improvements that are pretty impressive

01:39:00.780 | that any practitioner of Wim Hof or tumor

01:39:02.620 | will be familiar with.

01:39:03.780 | Is that pattern of breathing even,

01:39:09.180 | can we say that it maps to what you're describing

01:39:11.540 | in some general sense?

01:39:13.580 | Well, the expert in this would be Gordon Mitchell.

01:39:17.500 | I would say it moves in that direction,

01:39:20.680 | but it's not as extreme, because I don't think

01:39:23.020 | you can get down to the levels of hypoxia

01:39:26.180 | that they do clinically.

01:39:28.400 | I know that our pals at our breath collective

01:39:32.060 | actually just bought a machine,

01:39:34.060 | 'cause you buy a machine that does this,

01:39:36.340 | and they bought it and they're gonna do their own

01:39:37.860 | self-testing to see whether or not this has any effect

01:39:40.820 | on anything that they can measure.

01:39:43.020 | Of course, you have to be concerned

01:39:44.820 | about self-experimentation,

01:39:46.340 | but I applaud their curiosity in going after it.

01:39:50.980 | - Hyperbaric chambers.

01:39:52.660 | I hear a lot nowadays about hyperbaric chambers.

01:39:55.060 | People are buying them and using them,

01:39:56.540 | and what are your thoughts on hyperbaric chambers

01:39:59.400 | as it relates to any of the-

01:40:00.460 | - Hyper or hypo?

01:40:01.700 | - Hyperbaric chambers.

01:40:03.100 | - Okay, so you're not talking about altitude.

01:40:04.420 | - No.

01:40:05.900 | - I don't really have much to say.

01:40:08.380 | I mean, your oxygen levels will probably go up a little bit,

01:40:12.380 | and that could have a beneficial effect,

01:40:14.340 | but that's way outside my area of confidence.

01:40:17.420 | - I think 2022, I think, is going to be the year

01:40:20.780 | of two things I keep hearing a lot about,

01:40:22.460 | which is the deliberate use of high salt intake

01:40:25.900 | for performance, increasing blood volume, et cetera,

01:40:29.100 | and hyperbaric chambers seem to be catching on

01:40:31.420 | much in the same way that ice baths were

01:40:33.780 | and saunas seem to be right now.

01:40:35.700 | But anyway, a prediction we can return to

01:40:37.740 | at some point.

01:40:39.500 | I want to ask you about some of the studies

01:40:43.980 | that I've seen out there exploring

01:40:46.540 | how deliberately restricting one's breathing

01:40:50.220 | to nasal breathing can do things like improve memory.

01:40:53.280 | There's a couple of papers in Journal of Neuroscience,

01:40:55.240 | which is a respectable journal in our field,

01:40:57.900 | one looking at olfactory memory.

01:40:59.500 | So that kind of made sense

01:41:01.260 | because you can smell things better through your nose

01:41:03.460 | than your mouth, unless you're some sort of elk

01:41:07.020 | or something where they can,

01:41:08.460 | presumably they have some sense of smell

01:41:10.260 | in their mouth as well.

01:41:11.580 | But humans generally smell with their nose.

01:41:13.840 | That wasn't terribly surprising,

01:41:15.280 | but there was a companion study that showed

01:41:17.460 | that the hippocampus, an area involved in encoding memories

01:41:21.140 | in one form or another, was more active, if you will,

01:41:25.460 | and memory and recall was better

01:41:28.620 | when people learned information while nasal breathing

01:41:31.060 | as opposed to mouth breathing.

01:41:32.300 | Does that make sense from any mechanistic perspective?

01:41:36.500 | - Well, given that there's a major pathway

01:41:40.020 | going from the olfactory system into the brain

01:41:42.980 | and you cut that, and not one from any receptors

01:41:49.480 | in the mouth, the degree of respiratory modulation

01:41:53.060 | you're gonna see throughout the forebrain

01:41:56.540 | is gonna be less with mouth breathing than nose breathing.

01:42:01.380 | So it's certainly plausible.

01:42:05.260 | I think there are a lot of experiments

01:42:10.260 | that need to be done to distinguish

01:42:19.160 | between the two that is the nasal component

01:42:23.480 | and the non-nasal component

01:42:25.180 | of these breathing-related signals.

01:42:27.720 | There's a tendency sometimes when you have a strong effect

01:42:31.800 | to be exclusive, and I think what's going on here

01:42:35.840 | is that there are many inputs that can have an effect.

01:42:39.440 | Now, whether they're parceled,

01:42:40.920 | that some affect this part of behavior

01:42:43.240 | and some affect that part of behavior

01:42:44.800 | remains to be investigated.

01:42:47.760 | There's certainly a strong olfactory component.

01:42:50.760 | My interest is trying to follow the central component

01:42:55.240 | 'cause we know that there's a strong central component

01:42:57.880 | in this.

01:42:58.720 | In fact, there's a strong central projection

01:43:00.640 | to the olfactory bulb.

01:43:02.740 | So regardless of whether or not there's any

01:43:04.860 | effluent in and out of the nose,

01:43:06.720 | there's a respiratory input into the olfactory bulb,

01:43:09.720 | which combines with the respiratory modulated signals

01:43:13.040 | coming from the sensory receptors.

01:43:15.280 | - Interesting.

01:43:16.280 | And as long as we are poking around, forgive the pun,

01:43:20.880 | the nose, what about one nostril versus the other nostril?

01:43:25.880 | I know it sounds a little crazy to imagine,

01:43:28.700 | but there have been theories in yoga traditions and others

01:43:32.120 | that breathing through one nostril

01:43:34.300 | somehow activates certain brain centers,

01:43:37.500 | maybe hemispherically one side of the brain versus the other,

01:43:40.040 | or that right nostril and left nostril breathing

01:43:42.500 | might differ in terms of the levels of alertness

01:43:46.460 | or calmness they produce.

01:43:48.100 | I'm not aware of any mechanistic data on that,

01:43:50.240 | but if there's anything worthwhile about right nostril

01:43:54.360 | versus left nostril breathing that you're aware of,

01:43:56.660 | I'd love to know.

01:43:57.520 | - Well, it's certainly plausible.

01:44:00.540 | I don't know of any data demonstrating it

01:44:02.800 | except the anecdotal reports.

01:44:04.800 | As you know, the brain is highly lateralized

01:44:09.820 | and we have speech on one side

01:44:12.740 | and a dominant hand is on one side.

01:44:16.480 | And so the notion that if you have this huge signal

01:44:20.300 | coming from the olfactory system

01:44:22.840 | and to some degree it's lateralized,

01:44:25.140 | it's not perfectly symmetrical, that is,

01:44:27.540 | one side is not going evenly to both sides,

01:44:31.020 | then you can imagine that once the signal gets distributed

01:44:35.560 | in a way that's not uniform,

01:44:39.380 | that the effectiveness or the response

01:44:41.900 | is gonna be particular to the cortex

01:44:44.660 | in which either the signal still remains

01:44:48.740 | or the signal is removed from.

01:44:50.620 | - I see.

01:44:52.420 | What are some of the other features of our brain and body,

01:44:56.860 | be it blinking or eye movements

01:44:59.740 | or ability to encode sounds

01:45:03.800 | or any features of the way that we function

01:45:08.380 | and move and perceive things that are coordinated

01:45:12.140 | with breathing in some interesting way?

01:45:15.080 | - Thank you for that question.

01:45:16.580 | Almost everything.

01:45:20.740 | So we have, for example, on the autonomic side,

01:45:24.340 | we have respiratory sinus arrhythmia.

01:45:26.860 | That is, during expiration, the heart slows down.

01:45:30.220 | Your pupils oscillate with the respiratory cycle.

01:45:34.180 | I don't know what the functional basis for that is,

01:45:37.660 | but they do oscillate with the respiratory cycle.

01:45:40.020 | - When we inhale, our pupils constrict, presumably,

01:45:42.400 | 'cause there's an increase in heart rate

01:45:44.520 | and sympathetic tone, I would think of constriction.

01:45:46.820 | I'm guessing as you relax, the pupil will get,

01:45:49.360 | then you exhale- - I think you're right,

01:45:51.200 | but I always get the valence of that.

01:45:54.560 | - Well, it's counterintuitive 'cause people wouldn't think

01:45:56.680 | that when the pupils get, I mean, it depends.

01:46:00.680 | I mean, you can get very alert and aroused for stress

01:46:04.700 | or for good reasons, and the pupils get wider,

01:46:08.180 | but your visual field narrows,

01:46:09.640 | and then the opposite is true.

01:46:10.780 | Anyway, I guess the idea is that the pupils

01:46:12.920 | are changing size, and therefore the aperture

01:46:15.480 | of your visual window is changing

01:46:16.760 | in coordination with breathing.

01:46:19.700 | - Your fear response changes with the respiratory cycle.

01:46:24.700 | - Tell us more about that.

01:46:26.560 | - Well, there's a paper by Zolano,

01:46:29.320 | which I think showed rather clearly

01:46:31.240 | that if you show individuals fearful faces,

01:46:34.560 | that their measured response of fearfulness

01:46:44.480 | changes between inspiration and expiration.

01:46:46.760 | You know, I don't know why, but it does.

01:46:50.560 | Your reaction time changes.

01:46:55.560 | So you talk about blinking,

01:46:58.120 | the reaction time changes between inspiration and expiration.

01:47:02.040 | If I asked you to punch something,

01:47:04.920 | the time will change between inspiration and expiration.

01:47:08.560 | In fact, I don't know the degree

01:47:10.500 | to which martial artists exploit that.

01:47:12.420 | You know, you watch the breathing pattern

01:47:14.040 | and your opponent will actually move slower

01:47:18.200 | during one cycle compared to the other.

01:47:21.000 | - Meaning as they're, in which direction?

01:47:23.960 | If they're exhaling, they can punch faster.

01:47:26.160 | - I have to say, I don't keep a table

01:47:29.240 | of which direction things move in,

01:47:31.440 | 'cause I'm out of the martial arts field now.

01:47:34.640 | - My vague understanding is that exhales on strikes

01:47:39.880 | is the more typical way to do that.

01:47:44.080 | And so as people strike, they exhale.

01:47:47.520 | - As you exhale, but there are other components

01:47:53.160 | to striking because you want to stiffen your rib cage,

01:47:57.320 | you want to make a valsalva maneuver.

01:47:58.740 | So that's, you know, both an inspiration and an expiration.

01:48:02.400 | It's at the same time.

01:48:03.600 | So I don't know enough about when you say during expiration,

01:48:09.600 | I would assume that when you make your strike,

01:48:11.960 | you actually sort of want to stiffen here,

01:48:14.280 | which is a valsalva-like maneuver.

01:48:16.360 | - And oftentimes they'll clench their fist

01:48:17.960 | at the last moment, because anyway,

01:48:19.660 | there's a whole set of motor things that we should,

01:48:22.800 | we can talk to some fighters.

01:48:24.320 | We know people who know fighters, so we can ask them.

01:48:27.640 | Interesting, what are some other things

01:48:30.000 | that are modulated by breathing?

01:48:31.760 | - You know, I think anything anyone looks at

01:48:37.240 | seems to have a breathing component

01:48:39.740 | because it's all over your brain.

01:48:43.960 | And it's hard to imagine it not being effective.

01:48:47.080 | Now, whether it's incidental or just background

01:48:52.080 | and doesn't really have any behavioral advantage is possible.

01:48:57.800 | In other cases, it might have a behavioral advantage.

01:49:01.000 | I mean, the big, this eye-opening thing for me,

01:49:06.360 | probably a decade ago, was digging into literature

01:49:10.640 | and seeing how much of cortical activity

01:49:15.640 | and subcortical activity had a respiratory

01:49:18.400 | modulated component to it.

01:49:20.500 | And I think a lot of my colleagues who are studying cortex

01:49:24.760 | are oblivious to this.

01:49:26.960 | And they find, I heard a talk the other day

01:49:32.000 | with a person we'll go on named,

01:49:33.720 | who find a lot of things correlated

01:49:36.680 | with a particular movement.

01:49:39.640 | And I think it all, when I looked, I said,

01:49:43.000 | "Gee, that's a list of things that are respiratory modulated."

01:49:46.200 | And rather than it being correlated

01:49:48.360 | to the movement they were looking at,

01:49:50.500 | I think the movement they were looking at

01:49:52.920 | was modulated by breathing, as was everything else.

01:49:56.040 | So there wasn't that the movement itself

01:49:58.280 | was driving that correlation,

01:49:59.880 | it was that they were all correlated to something else,

01:50:02.440 | which is the breathing movement.

01:50:04.080 | And whether or not that is a behaviorally relevant

01:50:07.680 | or behaviorally something you can exploit, I don't know.

01:50:11.600 | - I suspect you're right, that breathing is,

01:50:15.000 | if not the foundational driver of many,

01:50:19.080 | if not all of these things,

01:50:20.120 | that it's at least one of the foundational drivers.

01:50:22.360 | - It's in the background, it's in the brain,

01:50:24.520 | and oscillations play an important part in brain function.

01:50:31.680 | And they vary in frequency from maybe 100 hertz

01:50:35.040 | down to, well, we can get to circadian

01:50:40.000 | and sort of monthly cycles.

01:50:42.740 | But breathing occupies a rather unusual place in all that,

01:50:47.740 | because, so let me talk about what people think

01:50:51.480 | the oscillations are doing, particularly the faster ones.

01:50:54.480 | They're important in coordinating signals across neurons.

01:51:00.320 | Just like in a computer, a computer steps.

01:51:03.480 | So a computer knows when information is coming

01:51:06.240 | from another part of a computer,

01:51:08.160 | that it was originated at a particular time.

01:51:11.880 | And so that discrete step-by-step thing

01:51:14.480 | is important in computer control.

01:51:16.000 | Now the brain is not a digital device,

01:51:18.280 | it's an analog device.

01:51:19.960 | But when I have a signal that coming in my ear and my eye,

01:51:24.840 | which is Andrew Huberman speaking,

01:51:26.840 | and I'm looking at his face, I see that as a whole,

01:51:30.360 | but the signal is coming into different parts of my brain,

01:51:33.000 | how do I unify that?

01:51:34.760 | Well, my neurons are very sensitive to changes

01:51:38.480 | in signals arriving by fractions of a millisecond.

01:51:41.960 | So how do I assure that those signals coming in

01:51:44.960 | represent the same signal?

01:51:47.240 | Well, if I have to have my brain in oscillation,

01:51:50.680 | and the signals ride on that oscillation,

01:51:53.920 | let's say the peak of the oscillation,

01:51:55.880 | I can then have a much better handle

01:51:58.400 | on the relative timing and say,

01:52:00.400 | those two signals came in at the same time,

01:52:03.000 | they may relate to the same object,

01:52:04.880 | and aha, I see you as one unified thing,

01:52:08.000 | spouting, you know, talking.

01:52:10.440 | And so these oscillations come

01:52:13.400 | in many different frequency ranges,

01:52:16.480 | and are important in memory formation

01:52:18.760 | and all sorts of things.

01:52:20.960 | I don't think people pay much attention to breathing

01:52:23.120 | because it's relatively slow to this,

01:52:27.080 | the range when you think about milliseconds.

01:52:30.440 | But we have important things

01:52:33.520 | that are thought to be important in cognitive function,

01:52:36.480 | which are a few cycles per second

01:52:39.400 | to 20, 30, 40, 50 cycles per second.

01:52:42.480 | Breathing in humans is maybe 0.2 cycles per second,

01:52:46.600 | every five seconds, although in rodents,

01:52:48.800 | they're up to four per second, which is pretty fast.

01:52:53.160 | So, but breathing has one thing which is special,

01:52:57.880 | that is, you can readily change it.

01:53:00.440 | So the degree to which the brain is using

01:53:03.080 | that slow signal for anything,

01:53:05.480 | if that becomes part of its normal signal processing,

01:53:09.920 | you now change it, that signal processing has to change.

01:53:16.240 | And as that signal processing changes,

01:53:20.400 | acutely, there's a change.

01:53:23.360 | So, you asked about breath practice,

01:53:26.440 | how long do you have to do it?

01:53:28.120 | Well, a single breath will change your state.

01:53:31.760 | You know, you're nervous, you take a deep breath,

01:53:36.120 | and it seems to help relax, so even a sigh.

01:53:39.560 | Call it what you will, call it what you will.

01:53:43.560 | It seems to work.

01:53:47.360 | Now, it doesn't have a permanent change,

01:53:50.280 | but you know, when I'm getting up to bat

01:53:52.000 | or getting up to the first tea or getting to give a big talk

01:53:54.600 | or coming to do a podcast, get a little bit anxious,

01:53:58.680 | a deep breath or a few deep breaths

01:54:00.920 | are tremendously effective in calming one down.

01:54:05.120 | And so, you can get a transient disruption,

01:54:10.120 | but on the other hand,

01:54:12.400 | let's take something like depression.

01:54:18.680 | I think you can envision depression

01:54:21.800 | as activity sort of going around in a circuit.

01:54:24.480 | And because it's continuous in the nervous system,

01:54:29.320 | as signals keep repeating, they tend to get stronger.

01:54:33.440 | And then get so strong, you can't break them.

01:54:37.480 | So, you can imagine depression being something

01:54:40.680 | going on and on and on, and you can't break it.

01:54:44.040 | And so, we have trouble when we get

01:54:46.440 | to certain levels of depression.

01:54:47.880 | I mean, all of us get depressed at some point,

01:54:50.320 | but if it's not continuous, it's not long lasting,

01:54:53.640 | we're able to break it.

01:54:55.360 | But if it's long lasting and very deep, we can't break it.

01:54:58.440 | So, the question is, how do we break it?

01:55:00.800 | Well, there are extreme measures to break it.

01:55:03.320 | We could do electroconvulsive shock.

01:55:06.440 | We shock the whole brain.

01:55:08.120 | That's disrupting activity in the whole brain.

01:55:10.440 | And when the circuit starts to get back together again,

01:55:14.600 | it's been disruptive.

01:55:15.720 | And we know that the brain, when signals get disrupted

01:55:19.440 | a little bit, we can weaken the connections.

01:55:22.680 | And weakening the connections, if it's then

01:55:24.520 | in the circuit involved in depression,

01:55:26.680 | we may get some relief.

01:55:27.880 | And electroconvulsive shock does work

01:55:30.840 | for relieving many kinds of depression.

01:55:33.400 | That's pretty heroic.

01:55:34.680 | Focal deep brain stimulation does the same thing,

01:55:39.920 | but more localized or transcranial stimulation.

01:55:43.680 | You're disrupting a network.

01:55:45.480 | And while it's getting back together,

01:55:47.640 | it may weaken some of the connections.

01:55:49.640 | If breathing is playing some role in this circuit,

01:55:54.920 | and now instead of doing like a one-second shock,

01:56:00.840 | I do 30 minutes of disruption by doing slow breathing

01:56:04.560 | or other breathing practice,

01:56:06.960 | those circuits begin to break down a little bit.

01:56:11.200 | And I get some relief.

01:56:13.280 | And if I continue to do it before the circuit

01:56:16.720 | can then build back up again,

01:56:18.680 | I gradually can wear that circuit down.

01:56:20.760 | I sort of liken this.

01:56:22.760 | I tell people it's like walking around on a dirt path.

01:56:25.800 | You build a rut, the rut gets so deep,

01:56:28.440 | you can't get out of it.

01:56:29.520 | And what breathing is doing is sort of filling in the rut

01:56:31.840 | bit by bit to the point that you can climb out of that rut.

01:56:35.760 | And that is because breathing, the breathing signal

01:56:40.400 | is playing some role in the way the circuit works.

01:56:45.160 | And then when you disrupt it,

01:56:47.080 | the circuit gets a little thrown off kilter.

01:56:49.720 | And as you know, when circuits get thrown off,

01:56:54.320 | the nervous system tries to adjust in some way or another.

01:56:57.640 | And it turns out at least for breathing,

01:57:01.080 | for some evolutionary reason or just by happenstance,

01:57:04.480 | it seems to improve our emotional function

01:57:06.840 | or our cognitive function.

01:57:08.520 | And we're very fortunate that that's the case.

01:57:12.080 | - It's a terrific segue into what I want to ask you next.

01:57:17.000 | And this is part of a set of questions

01:57:20.400 | I want to make sure we touch on before we wrap up,

01:57:23.920 | which is what do you do with all this knowledge

01:57:27.800 | in terms of a breathing practice?

01:57:29.720 | You mentioned that one breath can shift your brain state

01:57:33.080 | and that itself can be powerful.

01:57:35.000 | I think that's absolutely true.

01:57:37.200 | You've also talked about 30 minute breath work practices,

01:57:40.080 | which is 30 minutes of breath work

01:57:41.520 | is a pretty serious commitment, I think,

01:57:45.560 | but it's doable.

01:57:47.320 | Certainly a zero cost except for the time in most cases.

01:57:52.320 | What do you see out there in the landscape of breath work

01:57:55.460 | that's being done that you like?

01:57:58.160 | And why do you like it?

01:57:59.840 | What do you think or what would you like to see more of

01:58:05.400 | in terms of exploration of breath work?

01:58:08.200 | And what do you do?

01:58:09.160 | - Well, I'm a relatively new convert to breath work.

01:58:16.120 | Through my own investigation of it,

01:58:19.640 | I became convinced that it's real.

01:58:22.300 | And I'm basically a beginner in terms of my own practice.

01:58:27.300 | And I like to keep things simple.

01:58:32.000 | And I think I've discussed this before.

01:58:35.000 | I liken it to someone who's a couch potato

01:58:37.540 | who's told they got to begin to exercise.

01:58:39.760 | You don't go out and run a marathon.

01:58:42.040 | So, you know, couch potato, you say,

01:58:44.200 | okay, get up and walk for five minutes and 10 minutes.

01:58:46.960 | And then, okay, now you're walking for a longer period.

01:58:49.860 | You begin to run.

01:58:50.840 | And then you reach a point and say, well, gee,

01:58:54.640 | I'm interested in this sport.

01:58:57.000 | And there may be particular kinds of practices

01:58:59.300 | that you can use that could be helpful

01:59:01.680 | in optimizing performance of that sport.

01:59:04.840 | I'm not there yet.

01:59:06.360 | I find I get tremendous benefit by relatively short periods

01:59:11.360 | between five and maybe 20 minutes of doing box breathing.

01:59:16.680 | It's very simple to do.

01:59:20.280 | I have a simple app, which helps me keep the timing.

01:59:24.840 | - Do you recall which app it is?

01:59:25.960 | Is it the Apnea Trainer?

01:59:27.540 | Is that the one?

01:59:28.380 | - Well, I was using Calm for a long time,

01:59:30.440 | but I let my subscription relapse

01:59:32.920 | and I have another one whose name I don't remember.

01:59:34.800 | But it's, so it's very simple and it works for me.

01:59:39.800 | Now trying this Tummo because I'm just curious

01:59:45.280 | and exploring it because it may be acting

01:59:47.880 | for a different way.

01:59:48.720 | And I want to see if I respond differently.

01:59:52.140 | So I don't have a particular point of view now.

01:59:57.920 | I have friends and colleagues who are into, you know,

02:00:01.100 | particular styles like Wim Hof.

02:00:03.600 | And I think what he's doing is great

02:00:06.080 | in getting people who are interested.

02:00:08.720 | I think the notion is that I would like

02:00:11.760 | to see more people exploring this.

02:00:15.160 | And to some degree, as you point out, 30 minutes a day,

02:00:19.000 | some of the breath patterns that some of these styles

02:00:24.000 | like Wim Hof are a little intimidating to newbies.

02:00:29.080 | And so I would like to see something very simple

02:00:31.560 | that people, what I tell my friends is look,

02:00:33.240 | just try it five or 10 minutes.

02:00:34.680 | See if you feel better, do it for a few days.

02:00:37.120 | If you don't like it, stop it, it doesn't cost anything.

02:00:40.080 | And invariably they find that it's helpful.

02:00:43.860 | I will often interrupt my day

02:00:47.560 | to take five or 10 minutes.

02:00:52.760 | Like if I find that I'm lagging, you know,

02:00:56.400 | there's a, I think there's some pretty good data

02:00:59.000 | that your performance after lunch declines.

02:01:03.560 | And so very often what I'll do after lunch,

02:01:06.240 | which I didn't do today is take five or 10 minutes

02:01:08.640 | and just sort of breath practice.

02:01:10.640 | - And lately, what does that breath practice look like?

02:01:13.400 | - It's just box breathing for five or 10 minutes.

02:01:15.440 | - And the duration of your inhales and holds and exhales

02:01:18.340 | and holds is set by the app, is that right?

02:01:20.260 | - Well, I do five seconds.

02:01:22.920 | - So five seconds, inhale, five second hold,

02:01:25.720 | five second exhale, five second hold.

02:01:28.000 | - And sometimes I'll do doubles.

02:01:30.000 | I'll do 10 seconds just because I get bored, you know,

02:01:35.000 | it's just, I feel like doing it.

02:01:37.680 | And it's very helpful.

02:01:42.440 | I mean, now that's not the only thing I do with respect

02:01:47.000 | to trying to maintain my sanity and my health.

02:01:49.440 | - No, I can imagine there'll be a number of things.

02:01:51.560 | Although you seem, because you seem very sane

02:01:54.080 | and very healthy, I in fact know that you are.

02:01:57.120 | Both of those things.

02:01:58.120 | - Well, you suspect that I am.

02:01:59.360 | - I suspect, but there's data.

02:02:01.780 | A while back, we had a conversation, a casual conversation,

02:02:07.080 | but you said something that really stuck in my mind,

02:02:08.960 | which is that it might be that the specific pattern

02:02:13.960 | of breath work that one does is not as important

02:02:18.360 | as experiencing transitions between states

02:02:22.020 | based on deliberate breath work or something to that extent,

02:02:25.640 | which I interpreted to mean that if I were to do

02:02:29.040 | box breathing with five second in, five second hold,

02:02:31.840 | five second exhale, five second hold for a couple of days,

02:02:35.160 | or maybe even a couple of minutes,

02:02:36.400 | and then switch to 10 seconds, or then switch to Tummo,

02:02:39.600 | that there's something powerful perhaps in the transitions

02:02:44.380 | and realizing the relationship between different patterns

02:02:47.040 | of breathing and those transitions.

02:02:48.280 | Much in the same way that you can get into one of these cars

02:02:52.840 | at an amusement park that just goes at a constant rate

02:02:55.000 | and then stops.

02:02:56.080 | Very different than learning how to shift gears.

02:02:58.660 | I used to drive a manual, I still can,

02:03:01.120 | so I'm thinking about a manual transmission,

02:03:02.560 | but even with an automatic transmission,

02:03:04.240 | you start to get a sense of how the vehicle behaves

02:03:07.200 | under different conditions.

02:03:08.800 | And I thought that was a beautiful seed

02:03:11.280 | for a potential breath work practice that,

02:03:13.360 | at least to my awareness, nobody has really formalized,

02:03:16.020 | which is that you introduce some variability

02:03:18.300 | within the practice that's somewhat random

02:03:20.780 | in order to be able to sense the relationship

02:03:23.120 | between different speeds and depths of inhales, exhales,

02:03:25.740 | and holds, and so forth.

02:03:27.040 | And essentially it's like driving around the track,

02:03:29.020 | but with obstacles at different rates,

02:03:31.880 | and braking, and restarting, and things of that sort.

02:03:33.960 | That's how you learn how to drive.

02:03:35.780 | What do you think about that?

02:03:37.200 | And if you like it enough,

02:03:39.760 | can we call it the Feldman protocol?

02:03:41.520 | - Oh, please.

02:03:42.360 | I was asked in this BBC interview once,

02:03:48.200 | why didn't I name it the Feldman complex

02:03:50.800 | instead of the pre-butzinger complex?

02:03:52.280 | Because I already have a Feldman complex.

02:03:54.080 | - Well, it sounds like a psychiatric disorder,

02:03:56.480 | but I think the primary effect

02:04:01.480 | is this disruptive effect, which I described.

02:04:06.280 | And, but the particular responses may clearly vary

02:04:11.280 | depending on what that disruption is.

02:04:14.620 | I don't know of any particular data

02:04:18.560 | which are some well-controlled experiments,

02:04:21.000 | which can actually work through

02:04:23.260 | the different types of breathing patterns,

02:04:25.580 | or simply with a box pattern, just varying the durations.

02:04:29.840 | I mean, Prayama is sort of similar,

02:04:32.120 | but the amount of time you spend

02:04:34.160 | going around the box is different.

02:04:35.860 | So I don't really have much to say about this.

02:04:38.820 | I mean, this is why we need

02:04:42.120 | better controlled experiments in humans.

02:04:44.960 | And I think this is where being able to study it in rodents,

02:04:49.000 | where you can have a wide range of perturbations

02:04:54.000 | while you're doing more invasive studies

02:04:58.400 | to really get down as to which regions are affected,

02:05:01.640 | how is the signal processing disrupted,

02:05:04.680 | which is still a hypothesis, but how it's disrupted,

02:05:07.640 | could tell us a lot about maybe there's a resonant point

02:05:12.320 | at which there's an optimal effect

02:05:14.280 | when you take a particular breathing practice.

02:05:17.200 | And then when we talked about the fact

02:05:21.040 | that different breathing practices

02:05:23.040 | could be affecting the outcome through different pathways.

02:05:26.880 | You have the olfactory pathway,

02:05:30.040 | you have a central pathway, you have a vagal pathway,

02:05:33.560 | you have a descending pathway,

02:05:35.440 | how different practices may change

02:05:40.400 | the summation of those things,

02:05:43.040 | because I think all those things are probably involved.

02:05:46.440 | And we're just beginning to scratch the surface.

02:05:49.480 | And I just hope that we can get serious neuroscientists

02:05:54.480 | and psychologists to do the right experiments

02:05:59.160 | to get at this, because I think there's a lot of value

02:06:02.640 | to human health here.

02:06:05.240 | - I do too, and it's one of the reasons

02:06:06.800 | my lab has shifted to these sorts of things in humans.

02:06:09.600 | I'm delighted that you're continuing to do

02:06:11.640 | the hardcore mechanistic work in mice

02:06:14.200 | and probably do work in humans as well if you're not already.

02:06:18.840 | And there are other groups, Apple Lab at UCSF

02:06:21.320 | and a number of, I'm starting to see some papers out there

02:06:23.560 | about respiration in humans a little bit,

02:06:25.520 | some more brain imaging.

02:06:26.840 | I can't help but ask about a somewhat unrelated topic,

02:06:32.920 | but it is important in light of this conversation

02:06:36.480 | because you're here.

02:06:37.760 | And one of the things that I really enjoy

02:06:40.520 | about conversations with you as it relates to health

02:06:44.280 | and neuroscience and so forth is that

02:06:47.120 | you're one of the few colleagues I have

02:06:51.120 | who openly admits to exploring supplementation.

02:06:56.120 | I'm a long time supplement fan.

02:07:00.000 | I think there's power in compounds,

02:07:04.760 | both prescription, non-prescription, natural, synthesized.

02:07:09.320 | I don't use these haphazardly,

02:07:11.480 | but I think there's certainly power in them.

02:07:13.680 | And one of the places where you and I converge

02:07:16.560 | in terms of our interest in the nervous system

02:07:18.240 | and supplementation is vis-a-vis magnesium.

02:07:22.860 | Now I've talked endlessly on the podcast and elsewhere

02:07:27.600 | about magnesium for sake of sleep

02:07:29.900 | and improving transitions to sleep and so forth,

02:07:33.140 | but you have a somewhat different interest in magnesium

02:07:37.640 | as it relates to cognitive function

02:07:39.480 | and durability of cognitive function.

02:07:41.880 | Would you mind just sharing with us a little bit

02:07:43.440 | about what that interest is, where it stems from,

02:07:46.280 | and because it's the Huberman Lab podcast

02:07:49.720 | and we often talk about supplementation,

02:07:51.360 | what you do with that information.

02:07:54.720 | - So I need to disclose that I am a scientific advisor

02:07:58.520 | to a company called Neurocentria,

02:08:00.320 | which my graduate student called Song Liu was CEO.

02:08:06.080 | So that said, I can give you some background.

02:08:08.680 | Guo Song, although when he was in my lab,

02:08:11.480 | worked on breathing, had a deep interest

02:08:13.440 | in learning and memory.

02:08:15.680 | And when he left my lab, he went to work for it

02:08:17.960 | with a renowned learning and memory guy at Stanford,

02:08:21.500 | Dick Chen.

02:08:23.020 | And when he finished there,

02:08:26.280 | he was hired by Susumu Tonogawa at MIT.

02:08:29.400 | - Who also knows a thing or two about memory.

02:08:31.180 | I'm teasing, Susumu has a Nobel for his work

02:08:34.340 | on immunoglobulins, but then is a world-class

02:08:37.440 | memory researcher.

02:08:38.520 | - Yeah, and more.

02:08:41.140 | - He's many things.

02:08:43.460 | - And Guo Song had very curious, very bright guy,

02:08:48.460 | and he was interested in how signals between neurons

02:08:53.560 | get strengthened, which is called

02:08:55.160 | long-term potentiation or LTP.

02:08:58.080 | And one of the questions that arose was if I have

02:09:03.740 | inputs to a neuron and I get LTP, is the LTP bigger

02:09:08.740 | if the signal is bigger or the noise is less?

02:09:16.040 | So we can imagine that when we're listening to something,

02:09:19.220 | if it's louder, we can hear it better.

02:09:21.160 | Or if there's less noise, we can hear it better.

02:09:23.420 | And he wanted to investigate this.

02:09:26.280 | So he did this in tissue culture of hippocampal neurons.

02:09:31.300 | And what he found was that if he lowered the background

02:09:36.300 | activity in all of the neurons, that the LTP he elicited

02:09:41.680 | got stronger, and the way he did that was increasing

02:09:47.500 | the level of magnesium in the bathing solution.

02:09:50.600 | This gets into some esoteric electrophysiology,

02:09:54.920 | but basically there's a background level of noise

02:09:59.100 | in all neurons, and that part of it is regulated

02:10:03.780 | by the degree of magnesium in the extracellular bath.

02:10:07.700 | - And you mean electrical noise.

02:10:10.540 | - Electrical noise, I'm sorry, electrical noise.

02:10:12.860 | And if you, in what's called the physiological range,

02:10:17.860 | which is between 0.8 and 1.2 millimolar,

02:10:22.700 | which don't worry about the number.

02:10:24.180 | - I can't believe I remember the millimolar

02:10:25.540 | of the magnesium in the bath.

02:10:26.860 | - I'm always frightened that I get, you know,

02:10:28.820 | I say micro or femto or something,

02:10:31.500 | I go off by several orders of magnitude,

02:10:33.500 | but so in that physiological range,

02:10:37.820 | there's a big difference in the amount of noise

02:10:40.780 | in a neuron between 0.8 and 1.2 millimolar.

02:10:44.540 | So he played around with the magnesium,

02:10:47.500 | and he found out that when the magnesium was elevated,

02:10:50.700 | there was more LTP.

02:10:52.700 | All right, that's an observation in a tissue culture.

02:10:55.060 | - Right, and I should just mention that more LTP

02:10:57.260 | essentially translates to more neuroplasticity,

02:11:00.180 | more rewiring of connections in essence.

02:11:03.580 | - So he tested this in mice

02:11:08.580 | and basically offered them a,

02:11:11.460 | he had control mice, which got a normal diet

02:11:16.180 | and one that had more than the rich magnesium

02:11:18.780 | and the ones that lived enriched with magnesium

02:11:22.260 | had higher cognitive function, lived longer,

02:11:25.820 | everything you'd want in some magic pill.

02:11:29.100 | Those mice did that, excuse me, rats.

02:11:32.460 | The problem was that you couldn't imagine

02:11:38.380 | taking this into humans because most magnesium salts

02:11:43.380 | don't passively get from the gut

02:11:46.700 | into the bloodstream into the brain.

02:11:49.020 | They pass via what's called a transporter.

02:11:52.660 | Transporter is something in a membrane that grabs

02:11:56.100 | a magnesium molecule or atom

02:12:00.460 | and pulls it into the other side.

02:12:02.980 | So if you imagine you have magnesium in your gut,

02:12:06.100 | you have transporters that pull the magnesium

02:12:08.020 | into the gut into the bloodstream.

02:12:10.260 | Well, if you had to take a normal magnesium supplement

02:12:14.300 | that you can buy at the pharmacy,

02:12:16.580 | it doesn't cross the gut very easily.

02:12:19.340 | And if you would take enough of it

02:12:21.420 | to get it in your bloodstream, you start getting diarrhea.

02:12:26.060 | So it's not a good way to go.

02:12:29.260 | - Oh, it is a good way to go.

02:12:30.460 | I couldn't help myself.

02:12:32.420 | - Well said.

02:12:35.140 | So he worked with this brilliant chemist, Fei Mao,

02:12:41.300 | and Fei looked at a whole range of magnesium compounds

02:12:48.140 | and he found the magnesium threonate was much more effective

02:12:52.660 | in crossing the gut blood barrier.

02:12:56.980 | Now, they didn't realize at the time,

02:12:59.660 | but threonate is a metabolite of vitamin C.

02:13:03.500 | And there's lots of threonate in your body.

02:13:05.740 | So magnesium threonate would appear to be safe.

02:13:09.300 | And maybe a part of the role or now they believe

02:13:14.140 | it's part of the role of the threonate

02:13:17.100 | is that it supercharges the transporter

02:13:19.900 | to get the magnesium in.

02:13:21.020 | And remember, you need a transporter at the gut,

02:13:25.260 | into the brain and into cells.

02:13:27.140 | So they gave magnesium threonate to mice who had...

02:13:33.500 | No, let me backtrack a bit.

02:13:37.140 | They did a study in humans.

02:13:40.260 | They hired a company to do a test.

02:13:43.940 | It was a hands-off test.

02:13:46.140 | It's one of these companies that gets hired

02:13:47.780 | by the big pharma to do their tests for them.

02:13:50.740 | And they got patients who were diagnosed

02:13:55.620 | as mild cognitive decline.

02:13:57.620 | These are people who had cognitive disorder,

02:14:00.180 | which was age inappropriate.

02:14:02.500 | And the metric that they use for determining

02:14:06.980 | how far off they were is Spearman's G factor,

02:14:11.700 | which is a generalized measure of intelligence

02:14:16.660 | that most psychologists accept.

02:14:19.180 | And the biological age of the subjects was,

02:14:25.820 | I think 51 and the cognitive age was 61

02:14:31.300 | based on the Spearman G's test.

02:14:32.860 | I should say the Spearman G factor

02:14:35.900 | starts at a particular level in the population

02:14:40.060 | at age 20 and declines about 1% a year.

02:14:44.420 | So sorry to say, we're not 20 year olds anymore.

02:14:48.660 | But when you get a number from that,

02:14:52.460 | you can put on the curve and see

02:14:53.820 | whether it's about your age or not.

02:14:56.100 | These people were about 10 years older

02:14:58.340 | according to that metric.

02:14:59.860 | And long story short, after three months,

02:15:06.060 | this is a placebo-controlled double-blind study.

02:15:09.620 | The people who were in the placebo arm

02:15:13.380 | improved two years, which is common for human studies

02:15:18.140 | 'cause of placebo effect.

02:15:19.540 | The people who got the compound

02:15:23.620 | improved eight years on average.

02:15:27.060 | And some improved more than eight years.

02:15:28.980 | They didn't do any further diagnosis

02:15:31.180 | as to what caused the mild cognitive decline.

02:15:32.900 | But it was pretty, it was extraordinarily impressive.

02:15:36.140 | - So it moved their cognition closer to their biological age.

02:15:38.500 | - Biological age, biological age.

02:15:40.660 | - Do you recall what the dose is of magnesium threonate?

02:15:44.340 | - It's in the paper and it's basically

02:15:46.620 | what they have in the compound which is sold commercially.

02:15:50.260 | So the compound which is sold commercially

02:15:53.240 | is handled by a nutraceutical wholesaler

02:15:58.240 | who sells it to the retailers

02:16:00.380 | and they make whatever formulation they want.

02:16:04.680 | But it's a dosage which is,

02:16:09.680 | my understanding, is readily tolerable.

02:16:12.560 | I take half a dose.

02:16:14.500 | The reason I take half a dose is that I had

02:16:17.480 | my magnesium, blood magnesium measured

02:16:19.960 | and it was low normal for my age.

02:16:25.840 | I took half a dose, it became high normal.

02:16:28.640 | And I felt comfortable staying in the normal range.

02:16:33.420 | But a lot of people are taking the full dose.

02:16:36.860 | And at my age, I'm not looking to get smarter.

02:16:42.900 | I'm looking to decline more slowly.

02:16:46.320 | And it's hard for me to tell you

02:16:48.940 | whether or not it's effective or not.

02:16:50.620 | - Well, you remembered the millimolar

02:16:52.280 | of the magnesium in the solution

02:16:54.460 | and on the high and low end.

02:16:55.880 | So I would say it's not a well-controlled study

02:16:59.840 | when it's an N of one,

02:17:00.940 | but it seems to be working.

02:17:04.240 | - When I've recommended it to my friends,

02:17:06.760 | academics who are not by nature skeptical, if not cynical,

02:17:11.760 | and I insist that they try it,

02:17:14.400 | they usually don't report a major change

02:17:17.800 | in their cognitive function.

02:17:19.160 | Although sometimes they do report,

02:17:20.860 | well, I feel a little bit more alert

02:17:23.240 | and my physical movements are better,

02:17:25.980 | but many of them report their sleep better.

02:17:28.760 | - And that makes sense.

02:17:30.780 | I think there's good evidence that three and eight

02:17:33.400 | can accelerate the transition into sleep

02:17:36.340 | and maybe even access to deeper modes of sleep

02:17:41.240 | for some people.

02:17:42.780 | For many people, actually,

02:17:44.340 | a small percentage of people who take three and eight,

02:17:46.320 | including one of our podcast staff here,

02:17:50.220 | have stomach issues with it.

02:17:52.540 | They can't tolerate it.

02:17:53.380 | I would say just anecdotally,

02:17:54.960 | about 5% of people don't tolerate three and eight well.

02:17:57.640 | You stop taking and then they're fine.

02:17:59.340 | It caused them diarrhea or something of that sort,

02:18:02.080 | but most people tolerate it well.

02:18:03.300 | And most people report that it vastly improves their sleep.

02:18:06.520 | And again, that's anecdotally.

02:18:07.640 | There are a few studies and they're more on the way,

02:18:10.680 | but that's very interesting because I,

02:18:13.000 | until you and I had the discussion about three and eight,

02:18:15.400 | I wasn't aware of the cognitive enhancing effects,

02:18:20.200 | but the story makes sense from a mechanistic perspective.

02:18:22.800 | And it brings you around to a bigger

02:18:25.760 | and more important statement,

02:18:27.080 | which is that I so appreciate your attention to mechanism.

02:18:32.080 | I guess this stems from your early training as a physicist

02:18:35.960 | and the desire to get numbers

02:18:37.440 | and to really parse things at a fine level.

02:18:40.880 | So we've covered a lot today.

02:18:43.520 | I know there's much more that we could cover.

02:18:45.280 | I'm going to insist on a part two at some point,

02:18:48.560 | but I really want to speak on behalf

02:18:51.300 | of a huge number of people and just thank you,

02:18:53.500 | not just for your time and energy and attention to detail

02:18:56.840 | and accuracy and clarity around this topic today,

02:18:59.460 | but also what I should have said at the beginning,

02:19:02.480 | which is that, you know,

02:19:03.500 | you really are a pioneer in this field

02:19:06.120 | of studying respiration and the mechanisms

02:19:09.160 | underlying respiration with modern tools

02:19:11.400 | for now for many decades, you know,

02:19:14.120 | and the field of neuroscience was one

02:19:17.280 | that was perfectly content to address issues

02:19:20.360 | like memory and vision and, you know,

02:19:23.480 | sensation, perception, et cetera.

02:19:24.800 | But the respiratory system was largely overlooked

02:19:27.940 | for a long time and you've just been steadily clipping away

02:19:31.640 | and clipping away and much because of the events

02:19:34.040 | of related to COVID and a number of other things

02:19:39.040 | and this huge interest in breath work

02:19:41.240 | and brain states and wellness,

02:19:43.440 | the field of respiration and interest in respiration

02:19:46.040 | has just exploded.

02:19:47.600 | So I really want to extend a sincere thanks.

02:19:52.080 | It means a lot to me and I know to the audience

02:19:55.440 | of this podcast that someone with your depth and rigor

02:19:58.020 | in this area is both a scientist and a practitioner

02:20:01.480 | and that you would share this with us, so thank you.

02:20:03.840 | - Well, I want to thank you.

02:20:05.420 | This is actually a great opportunity for me.

02:20:07.640 | I've been isolated in my silo for a long time

02:20:11.560 | and it's been a wonderful experience to communicate

02:20:15.660 | to people outside the silo, have an interest in this

02:20:18.320 | and I think that there's a lot that remains to be done

02:20:21.560 | and I enjoy speaking to people who have interest in this.

02:20:24.880 | I find the interest to be quite mind boggling

02:20:28.600 | and it's quite wonderful that people are willing

02:20:31.840 | to listen to things that can be quite esoteric at times,

02:20:36.840 | but it gets down to deep things about who we are

02:20:41.540 | and how we are going to live our lives.

02:20:43.200 | So I appreciate the opportunity

02:20:44.860 | and I would be delighted to come back at any time.

02:20:48.920 | - Wonderful, we will absolutely do it.

02:20:50.720 | Thanks again, Jack.

02:20:51.820 | - Bye now.

02:20:53.320 | - Thank you for joining me for my conversation

02:20:55.200 | with Dr. Jack Feldman.

02:20:56.740 | I hope you found it as entertaining

02:20:58.520 | and as informative as I did.

02:21:00.880 | If you're learning from and or enjoying this podcast,

02:21:03.480 | please subscribe to us on YouTube.

02:21:05.240 | That's a terrific zero cost way to support us.

02:21:07.740 | In addition, please subscribe to the podcast

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02:21:13.980 | and you can leave us up to a five star rating.

02:21:16.680 | Please also check out the sponsors mentioned

02:21:18.520 | at the beginning of the podcast.

02:21:20.120 | That's the best way to support this podcast.

02:21:22.520 | We also have a Patreon, it's patreon.com/andrewhuberman.

02:21:26.200 | And there you can support the Huberman Lab Podcast

02:21:28.680 | at any level that you like.

02:21:30.600 | In addition, if you're not already following us

02:21:32.620 | on Instagram and Twitter,

02:21:34.360 | I teach neuroscience on Instagram and Twitter.

02:21:36.760 | Some of that information covers information

02:21:38.980 | covered on the podcast.

02:21:40.160 | Some of that information is unique information

02:21:42.480 | and that includes science and science-based tools

02:21:45.280 | that you can apply in everyday life.

02:21:47.040 | During today's podcast and on many previous podcast episodes,

02:21:50.640 | we talk about supplements.

02:21:51.960 | While supplements aren't necessary for everybody,

02:21:54.280 | many people derive tremendous benefit from them.

02:21:56.920 | One of the key issues with supplements,

02:21:58.440 | if you're going to take them,

02:21:59.800 | is that they be of the utmost quality.

02:22:01.840 | For that reason, the Huberman Lab Podcast

02:22:03.520 | has partnered with Thorne, T-H-O-R-N-E.

02:22:06.600 | Thorne supplements are of the very highest quality,

02:22:09.040 | both with respect to the quality

02:22:10.980 | of the ingredients themselves

02:22:12.320 | and the precision of the amounts of the ingredients.

02:22:14.660 | Why do I say that?

02:22:15.500 | Well, many supplement companies out there

02:22:17.340 | list amounts of particular substances on the bottle

02:22:20.540 | and when they've been tested,

02:22:21.620 | they do not match up to what's actually in those products.

02:22:25.020 | Thorne has the highest levels of stringency for quality

02:22:27.860 | and the particular amounts that are in each product.

02:22:31.940 | They partnered with the Mayo Clinic

02:22:33.460 | and all the major sports teams,

02:22:34.540 | so there's tremendous trust in Thorne products.

02:22:36.740 | That's why we partnered with them.

02:22:38.140 | If you're interested in seeing the supplements that I take,

02:22:40.100 | you can go to thorne.com/u/huberman.

02:22:43.940 | You can see the supplements that I take from Thorne.

02:22:46.140 | If you purchase any of those supplements there,

02:22:48.100 | you can get 20% off.

02:22:49.620 | And if you navigate further into the Thorne site

02:22:51.920 | to see the huge array of other products that they make,

02:22:54.320 | if you go in through thorne.com/u/huberman,

02:22:57.260 | you'll also get 20% off any of the products

02:22:59.460 | that Thorne makes.

02:23:00.640 | I also want to just mention one more time,

02:23:03.060 | the program that I mentioned

02:23:04.140 | at the beginning of the episode,

02:23:05.300 | which is Our Breath Collective.

02:23:06.800 | The Our Breath Collective has an advisory board

02:23:09.380 | that includes people like Dr. Jack Feldman,

02:23:11.460 | where you can learn detailed breath work protocols.

02:23:14.180 | If you're interested in doing or teaching breath work,

02:23:16.420 | I highly recommend checking it out.

02:23:18.140 | You can find it at ourbreathcollective.com/huberman,

02:23:21.500 | and that will give you $10 off your first month.

02:23:24.360 | So I want to thank you once again

02:23:25.420 | for joining me for my conversation with Dr. Jack Feldman.

02:23:28.060 | And last, but certainly not least,

02:23:30.220 | thank you for your interest in science.

02:23:31.980 | [upbeat music]

02:23:34.560 | [MUSIC PLAYING]

Dr. Jack Feldman: Breathing for Mental & Physical Health & Performance | Huberman Lab Podcast #54

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