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