82__transcript.txt

- [Andrew Huberman] Welcome
to the Huberman Lab Podcast,
where we discuss science
and science-based tools
for everyday life.
[bright music]
- I'm Andrew Huberman,
and I'm a professor of
neurobiology and ophthalmology
at Stanford School of Medicine.
Today, we're going to talk
about the Neuroscience of fear.
We are also going to talk about trauma
and post-traumatic stress disorders.
The Neuroscience of fear has
a long history in biology
and in the field of psychology.
However, I think it's fair to
say that in the last 10 years,
the field of Neuroscience has
shed light on not just the
neural circuits, meaning
the areas of the brain
that control the fear response
and the ways that it does it,
but some important ways
to extinguish fears
using behavioral
therapies, drug therapies,
and what we call brain machine interfaces.
Today, we are going to
talk about all of those,
and you're going to come away
with both an understanding
of the biology of fear and trauma,
as well as many practical tools
to confront fear and trauma.
In fact, we are going to discuss
one very recently published study
in which five minutes a day
of deliberate exposure to stress
was shown to alleviate
longstanding depressive
and fear related symptoms.
We will get into the details
of that study and the protocol
that emerges from that study
a little later in the podcast.
But it stands as a
really important somewhat
counter-intuitive example of
how stress itself can be used
to combat fear.
To give you a sense of where we are going,
I'll just lay out the
framework for today's podcast.
First, I'm going to teach
you about the biology of fear
and trauma.
Literally the cells and circuits
and connections in the body
and chemicals in the body that
give rise to the so-called
fear response.
And why sometimes, but not
always fear can turn into trauma.
I will also describe the
biology of how fear is unlearned
or what we call extinguished.
And there too, you're going
to get some serious surprises.
You're going to learn for instance,
that we can't just eliminate fears.
We actually have to replace
fears with a new positive event.
And again, there are tools
with which to do that,
and I will teach you those tools today.
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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So what is fear?
Well, fear falls into a category
of nervous system phenomenon
that we can reliably call
an emotion.
And it is hotly debated nowadays.
And it's been hotly debated
really for centuries
what an emotion is and
what an emotion isn't.
Now that's not a debate that
I want to get into today.
I think it's fair to say
that emotions include
responses within our body.
Quickening of heart rate,
changes in blood flow,
things that we experience as a warming
or a cooling of our skin.
But that there's also
a cognitive component.
There are thoughts, there are memories.
There's all sorts of stuff
that goes on in our mind
and in our body that
together we call an emotion.
And there's a vast amount of
interest in literature devoted
to try and understand how many
different emotions there are,
how different people experience emotions.
And that's certainly a
topic that we will embrace
in a future podcast episode.
But today I just want to talk
about fear as a response.
Because when we talk about fear
as a physiological response
and as a cognitive response,
then we can get down to some
very concrete mechanisms
and some very concrete and practical tools
that can be used to deal with
fear when fear is not wanted.
So let's talk first about what fear isn't.
Most people are familiar with stress,
both as a concept and as an experience.
Stress is a physiological response.
It involves quickening of the heart rate.
Typically quickening a breathing,
blood flow getting
shuttled to certain areas
of the brain and body and not to others.
It can create a hypervigilance
or an awareness.
Typically that awareness is narrower,
literally narrower in space,
like a soda straw view of the world
than when we are relaxed.
And it is fair to say
that we cannot have fear
without having several,
if not all of the elements
of the stress response.
However, we can have
stress without having fear.
Likewise, people are
familiar with the phrase
or the word rather, anxiety.
Anxiety tends to be stress
about some future event,
although it can mean other things as well.
We can't really have fear
without seeing or observing
or experiencing some of
the elements of anxiety,
but we can have anxiety
without having fear.
So what you're starting to
realize is that fear is built up
from certain basic elements
that include stress and anxiety.
And then there is trauma.
And trauma also requires a specific,
what we will call operational definition.
An operational definition is
just a definition that allows
us to have a conversation
because we both agree on
or mostly agree on what the
meaning of a given word is.
It makes conversations much easier.
In fact, I would argue if we
all had operational definitions
for more things in the world,
that there would be fewer
misunderstandings and arguments
and we'd all move a lot
further as a species.
But that's another topic entirely.
The operational definition of trauma
is that some fear took place,
which of course includes
stress and anxiety.
And that fear somehow gets embedded
or activated in our nervous system,
such that it shows up at
times when it's maladaptive.
Meaning that fear doesn't serve us well
and it gets reactivated at various times.
Like when you first
wake up in the morning,
if you're not in the presence
of something that scared you,
but you suddenly have what
feels like a panic attack
and you're in deep fear.
Well, that's post-traumatic stress.
That's post-traumatic fear.
So I don't want to get bogged down
too much in the nomenclature
but what I'm doing here is building up
a sort of a series of layers
where stress and anxiety
form the foundation of what
we're calling fear and trauma.
And then there are other phrases out there
that we would be remiss if
we didn't mention things
like phobias and panic attacks.
Panic attacks are the
experience of extreme fear
but without any fear inducing stimulus.
So it's kind of like trauma.
And a phobia tends to be extreme
fear of something specific.
Fear of spiders, fear of
heights, fear of flying,
fear of dying, these
kinds of things, okay?
The reason for laying all that
out there is not to create
a word soup to confuse us rather
it is to simplify the issue
because now that we
acknowledge that there are many
different phrases to describe
this thing that we call fear
and unrelated phenomenon.
We can start to just focus
on two of these issues,
fear and trauma.
As it relates to specific
biological processes,
specific cognitive processes.
And we can start to dissect
how fears are formed,
how fears are unformed
and how new memories
can come to replace previously
fearful experiences.
So in this effort to
establish a common language
around fear and trauma,
I want to point out autonomic arousal.
Autonomic arousal relates to this aspect
of our nervous system,
that we call the autonomic nervous system.
Autonomic means automatic
that somewhat of a misnomer,
because there are aspects of
your autonomic nervous system
that you can control.
But your autonomic nervous
system controls things like
digestion, urination,
sexual behavior, stress.
When you want to be awake,
when you want to be asleep,
it basically has two branches to it.
Two branches, meaning
two different systems.
One is the so-called sympathetic
autonomic nervous system.
Has nothing to do with sympathy,
it has everything to do
with increasing alertness.
Think of the sympathetic nervous system
as the alertness nervous system.
It's what ramps up your
levels of alertness,
ramps up your levels of vigilant.
Think about it as the
accelerator on your alertness
and attention.
The other branch of the
autonomic nervous system
is the so-called,
parasympathetic branch of
the autonomic nervous system.
I know that's a mouthful.
The parasympathetic branch of
the autonomic nervous system
are the cells and neurons and chemicals
and other aspects of your brain and body
that are involved in the
calming nervous system.
So sympathetic is alerting,
parasympathetic is calming.
And it acts as sort of a seesaw
to adjust your overall level of alertness.
So for instance, right now I'm alert,
but I feel pretty calm.
I'm not ready to go to
sleep or anything like that.
I don't feel like I need a nap.
I'm alert, but I'm calm.
I'm not in a state of stress or panic.
So that seesaw we could
imagine is more or less level.
Maybe it's tilted up a little bit
to the side of increased
sympathetic or alertness
rather than parasympathetic
because I feel wide awake.
If I were sleepy, the
opposite would be true.
The parasympathetic side
would be increased relative
to the sympathetic side.
There are many different aspects
of the autonomic nervous system,
but one of the main aspects is an aspect
that's going to come up again
and again and again today,
it's very important that
you understand what it is.
It's called the HPA axis.
The HPA axis stands for
Hypothalamic-Pituitary-Adrenal Axis.
The hypothalamus is a
collection of neurons.
It's an area of your brain real estate,
that's deep in the brain
at the base of the brain
that contains many, many different areas
that control things like temperature,
and desire to have sex,
desire to eat, thirst.
It also controls the desire
to not mate, to have sex,
not to eat, not drink more water
or any other type of fluid.
So it has accelerators and
brakes in there as well.
The hypothalamus connects
to the so-called pituitary,
the pituitary lives close
to the roof of your mouth.
It releases hormones
into your bloodstream.
And so the hypothalamus
has this ability to trigger
the release or prevent the
release of particular hormones
like cortisol or the hormones
that go stimulate ovaries
to produce estrogen or testes
to produce testosterone
or adrenals to produce Adrenaline.
And speaking of the adrenals
that [indistinct] and the HPA
are the adrenals.
You have two glands that
sit above your kidneys
and your lower back.
They receive signals by
way of nerve cells neurons,
and by way of hormones and other things
released from the brain
and elsewhere in the body.
And they release different hormones
and other types of
chemicals into the body.
And the two main ones that
you need to know about today
are Adrenaline also called
Epinephrine and Cortisol.
Both of those are
so-called stress hormones,
but they're not always involved in stress.
They're also involved in
waking up in the morning
when you arrive...
Excuse me, when you rise from sleep.
And so this HPA axis,
should be thought of in the following way.
The HPA axis includes
a piece of the brain,
the hypothalamus, the
pituitary, and the adrenals.
So it's a beautiful three part system
that can use your brain to
alert or wake up your body
and prepare it for action.
And it can do that in the short term,
by triggering the release
of hormones and chemicals
that make you alert and
ready to go right away
and by triggering the
release of neurotransmitters
and hormones and other chemicals
that give that alertness a very long tail,
a very long latency before it shuts off.
And that's important because
one of the hallmarks of fear
and one of the hallmarks of trauma
is that they involve fear
responses that are long lasting.
Even if those fearful events,
the events in the world
that trigger the HPA axis
can be very brief, like a
car that almost hits you
as you step off the curb or something...
A gunshot that goes off suddenly,
and it's just a very quick,
like, you know, 500
millisecond or 1 second event.
The fear response can
reverberate through your system
because the chemicals that
are involved in this HPA axis
have a fast component and
a longer-lasting component.
And the longer-lasting
component can actually change
not just the connections of
different areas of the brain
and the way that our
organs work like our heart
and the way that we breathe.
It actually can feed back to the brain
and literally control gene expression.
Which can take many days
and build out new circuits
and new chemicals that can embed
fear in our brain and body.
And that might sound very
depressing but there's a reason.
And there's an adaptive
reason why there's the slow
and fast phase of the HPA
axis and the fear response.
And fortunately, that gene expression
and the long arc of the fear response,
the way it kind of lives in our system
kind of like a phantom in some
ways can also be leveraged
to undo the fear response,
to extinguish the fear
response and replace it
with non fearful associations.
So let's dig a little deeper
into the neural circuits
and biology of fear.
Because in doing that,
we can start to reveal the
logic of how to attack fear
if that's the goal.
We can't have a discussion about fear
without discussing the famous amygdala.
Famous because I think most people by now
have heard of the amygdala.
Amygdala means almond.
It's an almond shaped structure
on both sides of the brain.
So you have one on the
right side of your brain,
and one on the left side of your brain.
The amygdala is part of what
we can call the threat reflex.
And this is very important
to conceptualize fear
as including a reflex.
So much as you have
reflexes that cause you
to lift your foot up
if you are just step on
something sharp.
You literally have a reflex
within your spinal cord
that causes you to lift up one
foot and extend the other one
toward the ground.
Believe it or not,
you always think you
step on something sharp
you pull your foot up.
But you actually step on something sharp,
you pull your foot up and in pulling it up
there's another reflex that's activated
that as you extend your other legs
so that you don't fall over.
Similarly in the process
of experiencing fear,
you have a reflex for particular events
in your brain and body.
And that reflex involves things like,
quickening of your heart
rate, hypervigilance,
your attentional systems pop on,
increased ability to access
energy stores for movement
and thought and so forth.
But just like that step on
the tack reflex example,
all of the neural circuits
that are associated
with being calm, with
being able to go to sleep,
with being able to
visualize the full picture
of your environment,
literally to see your entire environment,
or to hear other things around you.
All of those get shut down when
the so-called threat reflex
gets activated.
And the amygdala is part
of the threat reflect
so much so that we can really say,
that it's the final common pathway
through which the threat reflex flows.
In other words,
the amygdala is essential
for the threat response.
But the threat reflex
and the threat response
is kind of a dumb response.
It's not a sophisticated
thing, it's very generic.
And this is also a very important point.
One of the beauties of the fear system
is that it's very generalizable.
It's not designed for you to
be afraid of any one thing.
Sure, there are some debates
and probably some good data out there
that support the fact that
human babies are innately,
meaning requires no learning.
Innately afraid of certain
things like heights,
or snakes or spiders.
There's debate about this.
And they depends on the
quality of the experiment,
et cetera.
But the real capacity of the fear system
is that we can become afraid of anything
provided that this threat
system is activated
in conjunction with some
external experience.
So the way I'd like you to
think about the amygdala
is not as a fear center,
but that it's a critical
component of the threat reflex.
I'd like you to also internalize the idea
that the threat reflex involves
this activation of certain systems
and suppression of all the systems
for calming the parasympathetic system.
And now I'm going to describe
the way that information flows
into and through this threat reflex.
And in doing that, it will
reveal how specific things,
like a spider, like a snake,
like a physical trauma,
like a car accident, like
a fear of public speaking,
whatever happens to scare
you or scare somebody,
how that gets attached to this reflex.
Because this reflex is very generic.
It doesn't really know
what to be afraid of.
It only knows how to
create this sensation,
this internal landscape
that we think of as fear.
So while the amygdala
might look like an almond,
it's actually part of
a much bigger complex
or collection of neurons
called the amygdaloid complex.
That complex has anywhere
from 12 to 14 areas
depending on who's...
Which neuroanatomist is naming
things and carving it up
in Neuroscience and in much of biology.
We like to joke that there are lumpers
and there are splitters.
So some people like to draw boundaries
between every little distinct difference
and say, "Oh, that's a separate area
and other people are lumpers."
And they say, "Well, listen,
you know why complicate things?
Let's lump those together."
I'm neither a lumper nor a splitter,
I'm somewhere in between.
I think the number 12 is a good number
in terms of the number of
different areas of the amygdala.
Why is that important to us?
Well, it turns out that
the amygdala is not just
a area for threat,
it's an area for generating
threat reflexes that integrates
lots of different types of information.
So for those of you that want to know,
I'm going to give you some
names, some nomenclature,
for those of you that don't,
you can tune out for this.
But basically information
from our memory systems,
like the hippocampus and
from our sensory systems,
our eyes, our ears, our
nose, our mouth, et cetera.
So taste information, vision,
auditory information, touch, et cetera.
Flow into the so-called lateral
portion of the amygdala.
Flows into...
Or the amygdaloid complex.
It flows into the lateral portion.
And then there are multiple
outputs from the amygdala.
And this is where things
get particularly interesting
because the outputs of the amygdala
have a lot of different areas,
but there are two main pathways.
One involves the hypothalamus,
which you heard about before
this collection of neurons
that control a lot of our
primitive drives for sex,
for food, for thirst and
for warmth, et cetera.
And it also feeds out to our adrenals.
Those glands that you learned
about a few minutes ago
to create a sense of alertness and action.
It also feeds out what I mean
by feeds out, by the way,
is there are neurons that send wires.
We call those wires axons connections.
Where they can release chemicals
and trigger the activation
of different brain areas.
So it feeds out to other
brain areas such as the PAG.
PAG is very interesting
for our discussion today.
It's the periaqueductal gray.
The periaqueductal gray contains neurons
that can trigger freezing,
can trigger the...
Some people talk about
the fawning response,
which has kind of an appeasing
response to traumatic events.
But some people outright freeze
in response to fear, right?
We've heard of fight or flight.
And indeed the pathway that I'm describing
can create a sense of fight
and cause people to want to lean in,
in an aggressive way to combat
things that they're afraid of
or flight to run away.
Essentially to avoid
by mobilizing the thing
that they feel they're threatened by.
Now, even in the absence of some threat,
somebody that has say a
fear of public speaking
might hesitate or move away from a podium
or hesitate or move away
from raising their hand.
If raising their hand meant
that they might be called on
and would be public speaking.
So there's fight and flight,
but there's also the freeze response.
And the freeze response is controlled by
a number of brain centers,
but the periaqueductal gray, the PAG,
is central for this freeze
response and neurons.
They're also create what are
called Endogenous opioids.
Many of you have heard
of the opioid crisis,
which is a crisis of
prescription medication
given out too broadly for
people that don't need it,
who are become addicted to opioids.
Those are Exogenous opioid.
But Endogenous opioids
are chemicals released
from neurons in the PAG
and from elsewhere in the body
that give us a sense of numbing.
They actually numb us against pain.
And you can imagine why biology
would be organized this way.
A threat occurs or something
that we perceive as a threat,
we're afraid of it.
And a natural analgesic
is released into our body
because there's likely
to be an interaction
that's very uncomfortable.
That's physically uncomfortable.
So it's like we have our
own Endogenous release
of these opioids and that's
occurring in the PAG.
The other area and again,
sorry to litter the conversation
with these names of structures,
but some people seem to enjoy
knowing these structures.
You're fine if you just
understand what the structures do.
If you want to know the names that's fine.
But the other structure
is the locus coeruleus.
The locus coeruleus
creates a sense of arousal,
by releasing Adrenaline,
Epinephrine and Norepinephrine,
or related chemical into the brain.
So basically the activation
of the amygdaloid complex
could be from any number
of different things,
a memory of something fearful.
An actual sensory experience
of something that's fearful.
And but then the fear
response itself is taking part
because of the threat
reflex gets activated.
And that threat reflex
then sends a whole set
of other functions into action.
Freezing, activation of the adrenals,
activation of locus coeruleus
for arousal and alertness,
activation of this endogenous pain system
or anti-pain system in the PAG.
That's one pathway out of the amygdala.
The other pathway out of the amygdala
is to a very interesting
area that typically
is associated with reward
and even addiction.
So this might come as a
surprise to many of you.
In fact, it came as a surprise to me.
I remember when these data were published,
but the amygdala complex
actually projects to areas
of the Dopamine system.
The so-called nucleus accumbens,
the mesolimbic reward pathway,
for those of you that want to look that up
or that remember from
the Dopamine episodes.
We have pathways in our
brain that are associated
with pursuit, motivation and reward.
And the neuromodulator
Dopamine is largely responsible
for that feeling of
craving, pursuit and reward.
And this threat center is
actually able to communicate with
and activate the Dopamine system.
And later you will realize
why that is very important
and why you can leverage
the Dopamine system
in order to wire in new memories
to replace fearful ones.
So I've been hitting you with
a lot of names of things,
but for the moment,
even if you're interested in
all the Neuroscience names
and structures and so forth.
I'd like you to just conceptualize
that you have a circuit in your brain,
meaning a set of cells and connections
that are arranged in the following way.
You have a threat reflex that
can be activated at any time
very easily, but what
activates that threat reflex
can depend on two things.
One are prior memories
coming from brain areas
that are involved in storage of memories,
or it can be immediate experiences.
Things are happening in the now, okay?
So were something fearful
to happen right now,
your threat reflux could be activated.
Where you to remember something very scary
that happened to you in the past?
Your threat reflex could be activated.
And that threat reflex
circuit has two major outputs.
One of the major outputs is
to areas that are involved in
the threat response, freezing
pain management and alertness.
And the other major output
is to areas involved
in reward, motivation
and reinforcement, okay?
There's a fourth component.
And I promise this is the last component
that we need to put into this picture
of the neural circuits for fear.
And this is a circuit that
involves an area of the brain
called the prefrontal cortex
and some of its subdivision.
So literally in the front.
And it's involved in what
we call top-down processing.
Top-down processing is the way
that your prefrontal cortex
and other areas of the brain
can control or suppress
a reflex, okay?
A good example of this would
be the step on the tack example
that I gave before.
So when you step on a tack,
you immediately pull up your foot
and you extend the other leg.
That's the reflex that prevents
you from injuring yourself
and from falling over.
However, if you wanted,
not that you would want to.
But if you wanted, you could for instance,
place your foot onto a tack
and decide not to pull your foot away.
It would be difficult.
And again, I don't
recommend that you do that,
but you could override that reflex, okay?
There are other examples of reflexes,
like for instance,
getting into cold water,
most people will start
to huddle their body.
Most people won't want to
get into the cold water.
Many people will jump out.
But all of that is reflexive.
And should you want to, you
could override that reflex
through top-down processing.
You could tell yourself,
"Oh, I heard on a previous
Huberman Lab Podcast,
or on an Instagram post
that cold water exposure
can be beneficial for metabolism
and resilience, et cetera."
And indeed it can, and you can
decide to get into the water
and to stretch out your
body, not to huddle,
and you can fight those reflexes, okay?
The fighting of reflex
is carried out through
top-down processing, largely
through the prefrontal cortex.
You provide a narrative.
You tell yourself, "I want to
do this or I should do this.
Or even though I don't want
to, I'm going to do it anyway."
So top-down processing
is not just for getting into cold water,
and it certainly isn't
for overriding reflexes
that can damage us like a
stepping on the tack example.
It is the way in which we can override
any number of internal reflexes,
including the threat reflex.
And the way that we do that
is by giving a new story
or a new narrative to this
experience that we call threat.
And you know the threat response,
the threat response is
quickening of the heart rate,
quickening of the breathing.
We don't generally like the feeling
of Adrenaline in our system.
Some people are so-called
Adrenaline junkies,
and they get a mixture of
Dopamine and Adrenaline
from certain high intensity events.
I confess in previous aspects of my life,
I've tended to like Adrenaline.
I don't think I was at the
extreme of thrill seeking,
but I'm somebody that for
instance, I tend to like...
I like roller coasters,
I've done various things
where I'm familiar with
and I enjoy the sensation
of Adrenaline in my body.
But I enjoy it because of
the alertness that it brings
and the hyperacuity that it brings,
many people don't feel that way.
In fact, most people
don't like the sensation
of a lot of Adrenaline in their system.
That it makes them feel very uncomfortable
and out of control.
We will do an entire
episode about Adrenaline
and Adrenaline junkies
and Adrenaline aversives
in the future.
But the threat reflex inevitably involves
the release of Adrenaline into the system.
And then it becomes a
question of whether or not
you remain still, move forward or retreat
from that Adrenaline experience.
And when I say the Adrenaline experience,
I mean the threat reflex.
So this fourth component of
fear is really our ability
to attach narrative, to attach a meaning
and to attach purpose to
what is by all accounts
and purposes, a generic response.
There's no negotiating
what fear feels like.
There's only negotiating what it means.
There's only negotiating
whether or not you persist,
whether or not you pause or
whether or not you retreat.
So this is usually the
point in the podcast
where I think people start asking,
"Okay, well, there's the biology,
there's the mechanism, there's the logic.
How do I eliminate fear?"
Well, it's not quite that simple.
Although by understanding
the logic and the mechanisms
by which these circuits are built,
we can eventually get to that place.
I do want to plant a flag
around a particular type of tool
or a logical framework around a particular
set of tools rather,
that we are going to build
out through this episode.
And based on what you now
know that the threat reflex
gets input and it has outputs
and it's subject to these
top-down processing events,
these narratives.
You should be asking yourself,
what sort of narratives should
I apply to eliminate fear?
Well, first let's take a step back
and just acknowledged the reality,
which is that fear is in some
cases, an adaptive response.
We don't want people eliminating fears
that can get them
injured or killed, right?
The reason that the fear threat response
and reflex exists at all
is to help us from dying,
to help us from making
really bad decisions.
It just so happens that a
number of things happened to us
that are not lethal, that don't harm us,
but that harm us from the inside.
And I think that and here
I'm borrowing language
from an excellent researcher
who's done important work
in this area at Harvard.
His name is Dr. Kerry Ressler.
He's both a medical doctor
and a PhD, so an MD-PhD.
He's the chief scientific
officer at McLean Hospital.
He's a professor of psychiatry
at Harvard Medical School,
and he's done extensive
and important work on fear.
I'm going to refer back
to Dr. Ressler's work
several times during this podcast,
including important and
super interesting work
on transgenerational passage of trauma.
He's a absolutely world-class biologist,
absolutely world-class clinician.
And Dr. Ressler has described
fear before as containing
a historical component.
So it's not just about a
readiness for things that might
injure us or kill us in
the immediate circumstance
but also protecting us for the future
because of our important need
and ability to anticipate.
And what he describes our
memories as protective
or memories as dangerous.
You know, some memories,
even if they evoke a sense
of fear in us are protective.
They protect us from making bad mistakes
that could get us injured or killed,
or put us into really
horrible circumstances.
Other memories are dangerous
because they create a
sense in us of discomfort,
and they tend to limit our behavior
in ways that are maladaptive.
That prevent us from having
healthy relationships to others,
healthy job relationships,
healthy relationship
to ourselves, frankly.
So this language of memories as protective
or memories as dangerous
in the context of fear
is not something that I said,
it's really something that
I lifted from Dr. Ressler
in one of his many impressive lectures.
And it's an important aspect of fear
because much of the fear
system is a memory system.
Is designed to embed a memory
of certain previous experiences in us.
Such that the threat reflex is activated
in anticipation of what
might happen, okay?
So let's talk for a second
about how certain memories
get attached to this fear system.
And this brings us to a beautiful
and indeed Nobel Prize winning aspect
of biology and physiology,
which is Pavlovian conditioning.
Many of you are probably
familiar with Pavlov's dogs
and the famous Pavlovian
conditioning experiments.
They go something like this.
And Pavlov did these
experiments and ring a bell,
a dog doesn't do much
in response to a bell.
It might attend to it
but it doesn't salivate typically
in response to the bell.
However, if you pair the ringing of a bell
with a presentation of food enough times,
the dog will salivate
in response to the food.
Eventually you take away the food,
you just rang the bell
and the dog will salivate
in response to the bell, okay?
So in the context of so-called
Pavlovian conditioning,
these things have names
like conditioned stimulus,
and unconditional stimulus and responses.
People often get these mixed up
and it can be a little confusing,
but I'm just going to make
it really simple for you.
The unconditioned stimulus
is the thing that evokes
a response unconditionally.
So food is the unconditioned stimulus
in the example I just gave.
A foot shock or a loud bang
would be the unconditioned
stimulus in a...
For instance say,
an experiment geared
toward exploring fear.
That unconditioned
stimulus is unconditional.
It unconditionally evokes a startle
or in the case of food salivating.
The bell in the previous
example is what we call
the conditioned stimulus or
the conditioning stimulus.
Sometimes people mix these up.
The condition stimulus is
paired with the thing that
naturally creates a response.
And then eventually the condition stimulus
creates the response itself.
You might think, well,
that just seems endlessly
boring and simple, but
this is actually the way
that our fear systems work.
Except unlike Pavlov's
dogs, you don't need many,
many pairings of a bell with
some unconditioned stimulus
in order to get a response.
You can get what's called
one trial learning.
And in this circuit that
involves the amygdala,
the threat reflex,
and all this other stuff that
I was talking about earlier,
the system is set up for learning.
It's set up to create memories
and to anticipate problems.
It's a very good system
because it was designed to keep us safe.
And so the way to think about
this is that for many people,
one intense experience,
one burn, one bad breakup,
one bad experience, public speaking.
One bad experience with somebody pet snake
or whatever it happens to
be can cause intense fear
in the moment, a long
[indistinct] experience of fear,
like trouble sleeping that
night and the following night.
Memories of the experience
that are troubling,
physiological responses
that are troubling.
Essentially it gets wired
in as a fear with one trial.
Which is quite different
than the other forms
of neuroplasticity.
Neuroplasticity, of course,
just being the nervous
system's ability to change
in response to experience.
Other forms of neuroplasticity
like learning a language, learning music,
learning math, those take a while.
We don't generally get one trial learning
to positive or neutral experiences.
We get one trial learning
to negative experiences.
So there's this asymmetry
in how we're wired.
So now you should understand
how classical conditioning
as it's called occurs.
You go to give a piano recital as a kid,
you sit down and you freeze up
and it's horribly embarrassing.
And even if you just freeze
up for a few seconds,
the heart rate increase
and the perspiring,
the sweating and the shame that you feel
leads you to want to
avoid playing instruments
or public displays of performances
for a long period of time
unless you do something to overcome it.
That's one trial learning.
Some people,
it tends to be more an
accumulation of experiences.
They have a bad relationship
that lasts an entire summer,
an entire year, or God forbid a decade.
And then they have what they feel
is of a general sense of fear
about closeness to others,
an attachment.
These are common fears
that people experience.
Fears can be in the short-term,
fears can be in the long-term,
they can be in the medium term.
Again, the fear system is very generic.
It's wired to include
memories that are very acute,
that happened within a
moment, or that include many,
many events in long periods of time.
That kind of funnel into a general sense
of relationships are bad
or this particular city
or location is bad.
So there's a key what we
call temporal component.
There's a component of the fear system
being able to batch many events in time
and create one specific fear
or take one very specific
isolated incident
that happened very briefly
and create one very large
general sense of fears.
And I'll give an example of the latter,
just to kind of flesh
this out a little bit.
I had a friend come
visit me in San Francisco
some years ago, and their
car got broken into.
Unfortunately, a frequent
occurrence in San Francisco
even in the middle of the day.
Never leave anything
your car in San Francisco
they'll break in, in the middle
of the day, doesn't matter.
Police can be having coffee right there
in front of them they'll still do it,
for reasons we could
discuss, this is a problem.
They got their belongings
taken and they decided
they were never coming
back to San Francisco.
This was an isolated
incident that forever colored
their view of the city.
Which I frankly,
understanding the fear system,
I can understand.
We can have isolated
incidents that wick out
to broad decisions about entire places,
or we can have many experiences
that funnel into very
specific isolated fears about
particular circumstances,
places and things.
So I like to think that by
now you have a pretty good
understanding of the
circuits that underlie
the threat reflex, the fear response,
and how we have top-down control,
meaning we can attach a
narrative to the fear response.
And that the fear response can be learned
in association with
particular events, okay?
I haven't really talked about
how the learning occurs.
And so I just want to take
a moment and describe that
because it leads right into our discussion
about how to eliminate fears,
and indeed how to replace fears
with more positive experiences.
There's a process in our nervous system
that we call neuroplasticity.
Neuroplasticity broadly defined
is the nervous system's ability to change
in response to experience.
But at a cellular level,
that occurs through a couple
of different mechanisms.
One of the main mechanisms
is something called
long-term potentiation.
Long-term potentiation
involves the strengthening
of particular connections between neurons.
The connection sites between
neurons we call synapses,
actually technically synapses are the gaps
between those connections.
But nonetheless, synapses are
the point of communication
between neurons and
those can be strengthened
so that certain neurons
can talk to other neurons
more robustly than they
happened to before.
And anytime we talk
about a particular event,
the car, the snake, the
public speaking, the trauma,
the horrible experience,
wiring into the fear system.
What we're talking about is a
change in synaptic strengths.
We're talking about
neurons that previously
did not communicate well,
communicating very well.
It's like going from a old
school dial up connection,
or even an old school telephone connection
or Morse code connection of communication
to high speed ethernet, okay?
To a 5G connection.
It gets faster, it gets more robust,
and it's very, very clear.
That's what happens when you
get long-term potentiation.
And long-term potentiation involves
a couple of cellular mechanisms
that are going to be
relevant to our discussion
about treatments to undue fear.
And I'll just throw out
a couple of the names
of some of those cellular
elements right now.
The main one is the
so-called N-M-D-A receptor,
N-methyl-D-aspartate receptor.
And what this is, is this
is a little docking site,
like a little parking slot on a neuron.
And when a neuron gets
activated very strongly
like from an intense event
in the example of my friend,
the intense event.
Almost certainly activated
and NMDA receptors
related to their concept of
protecting their property
in their cars, the break into their car
caused the NMDA receptor to be activated.
Normally that NMDA receptor
is not easily activated
when it is activated
it sets off a cascade,
a series of signals within those neurons
that change those neurons.
It changes the genes they express,
it shuttles more parking spots
to the surface of those cells
so that the communication to
those cells becomes easier,
it becomes faster.
And so the way to think
about the NMDA receptor
is it's used sometimes for normal things
that we do every day,
making cups of coffee
and things like that.
But it's often used for learning.
It's used for creating a new associations
in our nervous system.
And so the activation of
the NMDA receptor and LTP,
and it involves some other things
that you may have heard of like,
brain-derived neurotrophic
factor and calcium entry,
things that we can leave for a
discussion for a future time.
But basically a whole cascade
of events happen within cells
that then make just even the
mere thought of something
or somebody or some event that happened
able to activate that threat reflex, okay?
So long-term potentiation is
one of the main mechanisms
by which we take formerly
innocuous or irrelevant events,
and we make them scary.
We make them traumatic.
Our neurons have mechanisms to do this.
Now, fortunately, the NMDA receptor
and long-term potentiation
can also run the whole system in reverse.
You can get what's called
a long-term depression,
and that doesn't have anything
to do with the depression
associated with low mood.
What we're talking about is
a weakening of connections.
You can go from having a very
high speed ethernet connection
between neurons, so to speak,
to a connection that's
more like Morse code,
or as like a poor dial up
connection or really weak signal.
And that's what's happening
when you extinguish a fear,
when you unlearn a fear.
So now I'd like to talk about
therapies that are carried out
in humans that allow fears to be undone,
that allow traumas to be reversed,
such that people no longer feel bad about
a particular person, place or thing.
Either real interactions with
that person, place or thing,
or imagine interactions with
that person, place or thing.
That process as I just mentioned
also involves things
like the NMDA receptor
but rather than
strengthening the connections
the first thing that has
to happen is there needs
to be a weakening of
connections that associate
the person, place or thing
with that threat reflex.
Subsequent to that,
we will see there needs
to be a strengthening
of some new experience
that's positive, okay?
This is a key element
of where we are headed
contrary to popular belief,
it is not going to work to
simply extinguish a fear.
One needs to extinguish
a fear and or trauma
and replace that fearful
or traumatic memory
or idea or response with
a positive response.
And this is something
that's rarely discussed
both in the scientific literature,
but certainly in the general discussion
around fear and trauma.
There's this idea that
we can extinguish fears,
we can rewire ourselves, we
can eliminate our traumas
and indeed we can.
But that process has to
involve not just becoming
comfortable with a particular
fearful event or trauma,
but also attaching a
new positive experience
to that previously fearful
or traumatic event.
There are a lot of different
approaches out there
that are in clinical
use to try and alleviate
fear and trauma and indeed PTSD,
post-traumatic stress disorder.
It might be surprising to learn
that many of those
treatments such as SSRIs,
the selective serotonin
reuptake inhibitor.
Things like Prozac and Zoloft and similar
and other antidepressants.
Or things like Benzodiazepines,
which are essentially like painkillers.
They create elevation in certain
transmitters in the brain
like GABA among others.
They can have a pain relieving effect.
They are generally however,
considered anxiolytics,
they reduce anxiety and
even antipsychotic drugs
or Beta blockers sometimes
called adrenergic blockers.
Drugs that are designed
to prevent the heart
from beating too fast or
to reduce blood pressure,
to reduce some elements
of the hypothalamic-pituitary
axis response
that we talked about earlier.
Many people experienced
some degree of relief
from the symptoms of
anxiety and fear and PTSD
in taking these various compounds.
Indeed, that's why they're
prescribed so broadly.
But you may find it interesting to note
that none of those current treatments
are based on the neurobiology of fear,
at least not directly, right?
People that take SSRIs
oftentimes will experience
a reduction in anxiety.
It depends on the dosage
and the individual of course, right?
And you have to work with
a doctor, a psychiatrist,
to determine whether or
not they're right for you
in the correct dosage, if
they are right for you.
But that modulation of
anxiety can indirectly
reduce the likelihood that
one will have a panic attack
or experience of fear, an
intense experience of fear
or reliving of a trauma.
But the SSRIs themselves are not plugging
into some specific mechanism
related to how fear
comes about in the system.
It's an indirect support.
That's important because if
the goal of modern psychiatry
and the goal of modern
biology is to provide
mechanistic understanding
that leads to treatments.
We need to think about what
are the sorts of treatments
that tap into the very fear circuits
that we described before.
The fact that there are memories attached
to a generic threat reflex and response.
And the threat reflex and
response can be linked up
with the Dopamine system
and can be linked up with other systems
that are involved in pain,
relief and anxiety and so forth.
And so that brings us to which treatments
are directly related to the fear circuitry
and the circuitry related to trauma?
And the primary one to
begin with is the so-called
behavioral therapies.
Now, oftentimes we all wish
I think from time to time
that there's some specific
pill that we can take
or there's some machine or device
that we can plug our finger into
or that we can put on a headset
and all of a sudden we just
rewire our nervous system.
Fear has gone, trauma's gone,
but it doesn't work that way.
And when we think of language
and narrative as a tool
to rewire our nervous system
in comparison to those
kinds of ideas about pills
and machines and potions,
it starts to seem a
little bit weak, right?
If we just think, "Oh,
well, how could talking
actually change the way that
we respond to something?"
But actually there are
three forms of therapy
that purely through the use of language
have been shown to have
very strong positive impact,
meaning reduce fears and traumas.
And those three are
prolonged exposure therapy,
cognitive processing, or CPT
and cognitive behavioral therapy.
And I not going to go
into the entire literature
around prolonged exposure,
cognitive processing,
and cognitive behavioral therapy.
But I will just illustrate
the central theme
that allows them to work.
Now, remember that the circuit for fear,
the circuit for trauma
involves this generic reflex.
And then there are those top-down elements
coming from the forebrain.
It's very clear because it's been measured
that if you look at the amount of anxiety,
the pure physiological anxiety response
of quickening of heart
rate, flushing of the skin,
sometimes quaking of the hands,
that the experience of fear over time
when people recount or retell their trauma
that the first time they do that
especially when it's
recounted in a lot of detail
there's a tremendous anxiety response.
Sometimes even as great or
greater than the actual exposure
to the fearful event or trauma.
And obviously this is
something that is done
with a clinician present,
because it is very
traumatic to the person.
They're literally reliving the
trauma in full rich detail,
and they are encouraged to
provide full rich detail.
They're often encouraged to
speak in complete sentences
to flush out details about
how they felt in inside,
to flush out details about their memories
going into this traumatic
or fearful event,
going through it.
And after really digging
into all the nuance
and contours of these
horrible experiences.
But what's remarkable is that
in the second and the third
and the fourth retelling
of these traumatic
or fearful events that anxiety response
and the amount of the
physiological response,
I should say that the
amplitude of the physiological
becomes progressively
diminished with each retelling.
Now, some of you might be saying,
"Well, duh, you know, you
tell a story enough times,
that eventually it wears off."
Just like if you watch
a movie enough times
and you hear the same joke enough times
eventually it doesn't
have the same impact.
But that [indistinct] be the case, right?
You could imagine that this
high amplitude anxiety response,
this high amplitude activation
of the sympathetic nervous
system in retelling
would actually create a even
deeper routed fear response
and trauma but that's not what happens.
And every clinician I
spoke to in anticipation
of this episode which include
clinical psychologists,
psychiatrists and people who actually
work on the fear system
at a biological level
said the exact same thing which is that,
"A detailed recounting of the traumatic
and fearful events is absolutely essential
in order to get the positive
effects of prolonged exposure,
cognitive processing and
cognitive behavioral therapy."
Again, this has to be done
with the appropriate support.
This isn't something that
should be taken lightly
because as we've mentioned before
the fear response can
have a very long lasting
contour to it.
People can sometimes have trouble sleeping
for days and days.
And afterwards we'll talk
about sleep in a little bit.
But the point is that the
retelling is important.
And the idea here is to
take what was a terrible
and extremely troubling,
meaning physiologically troubling,
psychologically troubling story,
and turn it into what
is essentially a boring,
bad story, okay?
It never really becomes a
good story at this point
in the treatment process
that we're describing.
So a terrible event is
a terrible event period.
But there's a way in which
the retelling of that event
starts to uncouple the threat
reflex from the narrative.
And with each successive
retelling in detail
of these traumatic events,
of these fearful events,
the threat reflex is
activated at a progressively
lower and lower amplitude.
Such that eventually it
just becomes a really bad,
really boring story.
Now that's one part of the
process of getting over a fear.
It's what we call fear extinction.
And we can bring ourselves
back to our earlier example
of Pavlovian conditioning,
because many studies have been done
both in animals and in
humans showing that,
for instance, if you pair
a tone, a bell or a buzzer
with a foot shock that
an animal or a person
will brace themselves for the foot shock.
Eventually you can just
give the bell or a tone
and the person will experience
that same freezing up
or the same fight or
flight or freeze response.
So you conditioned that.
But if you give the tone
or the bell over and over,
and there's no foot
shock, there's no pain,
and in human [indistinct]
sometimes I'm with foot shocks,
sometimes believe it
or not with mild burn,
even some studies, there is older studies
you couldn't do those now,
nor would you want to.
But eventually what happens is the tone...
The bell no longer evokes
that response, okay?
So you see this as a reversal
of the classical conditioning
and we call that reversal extinction.
So the retelling of this traumatic
or fearful narrative, excuse me,
fearful narrative is essentially
an extinction process.
Now, how is this done?
One can do this in a
therapist office face-to-face,
that's sometimes done.
It's sometimes done in group type settings
where people actually stand up
or sit in front of a group small or large
and recount in detail
their traumatic experience.
It's sometimes done by people writing out
the experience in detail.
And which one of these
is the most effective?
Isn't really clear.
The literature points to the
fact that a feeling of trust
obviously between the
patient and the clinician
or the person and the group is essential.
Some people don't have
access to because of finances
or other limitations to
therapy of that sort.
In that case, journaling in detail
has been shown to be effective.
Although, again, I want to caution people
about reactivating traumas
without consideration
for the kinds of social
support they might need
around that reactivation.
And we will talk a little bit later about
some of the chemicals
involved in social support
and why those help extinguish fears.
So the thing to embed in
your mind is that recognition
of the early traumatic or
fearful event in detail
over and over is key to forming
a new non-traumatic association
with that event or person.
So that's part one, you need
to diminish the old experience.
And when I say diminish,
I mean, reduce the amplitude
of the physiological response.
Now this is just but one approach.
I'm going to talk about other approaches
to eliminating fear and
trauma as we go forward.
But I want to emphasize that
diminishing the amplitude
of the physiological
response is the first step.
So it's like a clearing
away of the association
between the person, place or
thing and that threat reflex.
But even after that's occurred,
there's an essential need
to relearn a new narrative.
Why is their essential need
to relearn a new narrative
or create a new association?
Well, that has to do with
that fear reflect circuitry.
As you recall, there outputs
two areas of the brain
that are associated with Dopamine
release and reinforcement.
And that we now know offers the capacity
for these fear circuits
in these circuits that underlie trauma
to be mapped onto new experiences
that are of positive association.
So I'm going to give a
kind of basic example.
It's a kind of a silly example,
but I'm giving it as a
template for what could be
any number of other different examples.
Example I'll give is
let's say a kid is biking
to play soccer, soccer practice,
and they get into a
bad car accident, okay?
Terrible thing to
happen, but they survive.
They recover.
And somehow...
And we really don't know
why certain fear memories
get wired in more
broadly or more narrowly.
Somehow this kid just doesn't
even want to bicycle anymore.
And they actually don't
even want to play sports.
And they actually just
don't want to go anywhere.
They're kind of isolating and
not interacting with friends
very much at all.
It's a pretty broad response.
It didn't have to be that way.
Some kids would just decide they
don't want to cycle any more
down that particular street.
Well, the process of
retelling the narrative
to a clinician would allow an extinction
of the fear response, right?
So a reduction in the heart rate,
a reduction in the narrowing of focus,
a reduction in all the
things that we consider fear.
But a really good cognitive
behavioral therapist
or somebody that understands
the Neuroscience of fear
and trauma would understand
that that's not sufficient.
That's what it's really
important is that this child,
this hypothetical child
relearn a new narrative
that they don't just manage
to bike to soccer practice
or manage to spend time with friends,
but that they actually start
wiring in new positive associations
with biking to practice,
with playing soccer,
with social events.
And, and this is the somewhat
surprising feature of this
and that they link that back
to that early traumatic experience.
That it's not just that they're replacing
that bad experience and memory
with a good experience and memory,
but they're actually holding in mind
in these top-down narrative
circuits, if you will.
They're holding in mind,
"Ah, I'm not just biking
to soccer practice.
I'm actually biking to soccer
practice and I'm enjoying it
despite the fact that I
was in a bad car accident.
Despite the fact that two
months ago or two years ago,
or maybe even 10 years ago,
I couldn't even leave my room
or I didn't want to
associate with anybody."
So the building up of the
positive associations are key.
And the linking of those
positive associations with the
earlier traumatic event is
key for the following reason,
the top-down circuitry
from the prefrontal cortex
to this threat reflex circuit
is not like the other
connections in that circuit.
The other connections in that circuit
are what we call
glutamatergic and excitatory.
They are all about
activating other neurons,
like a chain reaction.
One neuron activates, the next activates,
the next like dominoes falling.
These top-down circuits that
feed into the threat reflex
and all its parts is
what we call inhibitory.
It tends to prevent activation
of those given circuitries.
It tends to prevent activation
of the threat reflex.
So it's acting as a break.
And so when we think
of positive experiences
being associated with what was previously
a negative experience,
we're not talking about
forgetting that the car
accident was horrible
or forgetting that the assault
was absolutely dreadful.
We're talking about attaching
a new positive memory
to the circuitry so that
the previous fear response
is far less likely to occur
and that it remains extinguished.
So just to make sure
this is absolutely clear,
there's a first step which
involves retelling and reliving
in order to extinguish
the fear and the trauma,
to reduce the amplitude of the response.
Then there's a need to replace or attach
positive experiences to the earlier
what would be traumatic response.
The extinction has to
go first, this is key.
You can't simply say, "Oh, you know,
the car accident was actually a good thing
because I stayed home a lot
that year and I got to study."
You can tell yourself that
and that could also be true.
But that won't necessarily
and probably won't
eliminate the fear or
the traumatic association
of the car accident.
And again, I'm using car
accidents as a general example
or a generic example here, okay?
So there's a three-part process.
One diminished the old experience through
repetitive narrative.
And almost inevitably
the initial repetition
of that is going to be very high amplitude
and quite troubling.
But over time it will reduce, right?
You're turning that terrible
really upsetting story
into a terrible boring story.
That's the extinction process.
Then there's a relearning
of a new narrative
that includes some sort
of sense of reward.
And that sense of reward
has to be tacked back
on to the traumatic event
or what was previously a traumatic event.
And that is all through narrative.
It's all through cognition.
And I think this is a
very important point.
Oftentimes I think we tend to undervalue
the importance of rationalization
and of story and of narrative.
But the prefrontal cortex
is this amazing capacity
of our brain real estate
to create meaning,
to attach meaning and purpose
to things that otherwise
are just reflexive.
And in the example of an ice bath,
it might be a little trivial.
In the example of the
kid with a car accident,
it becomes a little more relevant.
And in the example of things
like people surviving,
you know, genocide or attaching
stories of great victory
to what were previously thought
of as stories of great loss
of time, of people, of
any number of things.
That process of narrative
is one of the major ways
that the human brain rewires itself.
Narrative should not be
undervalued as a tool
for relieving fear and trauma.
In fact, narrative is one of the best
and most potent ways that we
can rewire our fear circuitry.
And that indeed we can form
completely new relationships
to things over time.
So basically narratives
should not be undervalued
as a tool to rewire our nervous system
but it has to be engaged
in the correct sequence.
And that correct sequence
is first extinction,
then relearning a new narrative
with positive associations
and attaching those positive associations
to the formerly traumatic
or fearful event.
Now I mentioned prolonged
exposure therapy,
cognitive processing, and
cognitive behavioral therapy.
For those of you that are
seeking relief from fear
and traumatic events,
you can look up licensed
clinicians that can carry out
those one or several of
those types of therapies.
I get a lot of questions
about other forms of therapy.
One of the ones that comes
up a lot is so-called
EMDR, Eye Movement
Desensitization and Reprocessing
developed by Francine Shapiro in the 80s.
Eye Movement Desensitization
and Reprocessing involves
moving the eyes side to side
while recounting a traumatic
or fearful narrative typically
with a clinician present.
Why would that work?
Well, basically when I
first heard about EMDR
from my stance as a vision scientist
I thought the whole
thing was kind of crazy
and half-baked frankly.
I heard these theories that,
"Oh, it recreates the eye movements
in rapid eye movement sleep or REM sleep."
And that's completely false.
It does not.
I heard the argument EMDR
activates both sides of the brain,
which I guess hypothetically
was thought to be important somehow.
And frankly, there's
no evidence whatsoever
that EMDR activates
both sides of the brain
in a way that's beneficial.
I mean, by looking from side to side,
just because of the way that
binocular vision circuits
are organized it will do that.
But it never made any sense
to me why EMDR would work
until several years ago when I saw.
Because I reviewed no
fewer than five papers.
Some in animal models, others in humans
looking at lateral eye movements.
Meaning I moving from side
to side with eyes open,
not eyes up or down.
And what was observed in these experiments
in all of them actually,
all five of those papers
was a dramatic reduction
in the activation and
actually an inhibition
a suppression of the fear
or threat reflect circuitry
which was a jaw dropper for me.
I thought, "Wow, it
actually was a jaw dropper."
I widened that.
For me, I thought, "Oh my goodness,
maybe this EMDR stuff works
according to some mechanism.
And maybe this is the mechanism."
And indeed many laboratories, not mine,
but many laboratories are
now pursuing that idea.
And it's looking very likely.
Why would that happen?
Well, just very briefly,
a lateralized eye movements of
the sort that I'm describing
and I'm moving my hand like this
but I'll just do it with my eyes
even though it's a little
embarrassing to do that.
Cause I know it looks
strange, I don't mind
cause I'm doing EMDR and
EMDR reduces activation
of the amygdala and related circuitries
which reduces anxiety
and reduces the amplitude
of the threat reflex.
Reduces sympathetic autonomic arousal.
In other words, we feel
calmer or we feel less alert,
less stressed when moving
our eyes from side to side.
I just heard a story about this is that
these are the sorts of
eye movements that we do
when we are ambulating,
moving through space,
through some sort of
self-generated motion.
And one can make up a
pretty reasonable story
in the evolutionary context
or ecological context
that forward movement and fear
are generally incompatible
with one another.
That generally a fear
response involves a freezing
or a retreating.
Some people will advance,
but that's usually a trained
advance in response to fear
so first responders and so forth.
Most people freeze or
retreat when they're afraid.
Forward movement generates
these eye movements.
It does seem to suppress
activation of this threat reflex
and the amygdala in particular.
So for the many EMDR
practitioners out there
these papers I think
are a great celebration.
And I think there is now
increasing excitement about EMDR
in the psychiatric and
psychological community
for its utility, for treating
fear, trauma and PTSD.
However, I should point
out that in discussing EMDR
with various colleagues of
mine at Stanford and elsewhere,
I was told that EMDR has
been shown to be beneficial
in particular for single
event type traumas
or fearful experiences.
Not so much for relieving the trauma
or feelings of fear associated.
For instance, with an entire bad marriage
or an entire childhood.
But more for single more acute
events that can be described
within a very kind of brief narrative.
Brief, not necessarily in time,
but that the car accident,
the bad interaction
with another individual,
the assault, God forbid,
these sorts of things.
And I realize we're down
in the weeds of topics
that are unpleasant.
And so I have great sensitivity to that
but I think it's also
important that we be realistic
about the kinds of things
that traumatize people.
So is EMDR useful?
Well, it seems like it
works for these single event
or kind of constrained event type traumas
that people can describe
while moving their eyes from side to side
generally in the presence of a clinician.
However, if we think back to the model
of how you extinguish and
then replace a trauma or fear,
remember you have to
diminish the old experience
the amplitude of that.
You need to...
That's the extinguish portion.
Then you need to relearn a new narrative
and attach reward to
the old traumatic event.
EMDR only really taps into the extinction
of the physiological response
to the old experience.
I'm sure that there are
EMDR practitioners out there
that are thinking about the attaching
of the new narrative and reward,
but there I've heard less
and I've seen fewer
peer-reviewed papers on that.
So let's think about this logically.
Let's say, and indeed it's the case
that I'm sitting down in a chair
and moving eyes side to side deliberately
for some period of time
reduces activation of the threat reflex.
I or the patient in this case,
recites or repeats over and
over the traumatic event
or the fearful event.
I'm doing that in the presence
of a lower amplitude response.
Remember back to where we
talked about how the retelling
works best if the first time it's done
there's a huge amplitude response.
And then with each successive
repeat that response
the threat response gets lower and lower.
With EMDR, you're sort of short circuiting
you're kind of sneaking around the corner
of that high amplitude response.
And so it's taking a
somewhat different approach
of trying to extinguish the bad feelings
in body and mind associated
with an experience
by reducing the physiological response.
So it's somewhat different.
And at least to my knowledge
and EMDR practitioners
please correct me, but
at least to my knowledge,
there isn't an active component to EMDR
of relearning a new narrative
and attaching reward.
Now reward and attaching reward requires
a somewhat high amplitude
sympathetic arousal.
It requires a feeling of a
victory which is arousal, okay?
It's positive arousal,
not negative arousal,
but it is arousal.
So I'm not focusing on
this to try and diminish
the potential impact of EMDR.
I know many people have
achieved great relief from EMDR
but it doesn't tap into all
the aspects of the extinction
and relearning that we
talked about previously.
And therefore, I think on its own
at least in many cases is
unlikely to be a complete therapy
for fear and trauma.
If there are people out there
who've had terrific results
with the EMDR, please let us
know in the comment section,
on YouTube would be the ideal place.
If you've had bad experiences with EMDR
or it didn't work for
you also let us know.
I think that EMDR practitioners
like most practitioners
in the psychiatric and psychological space
are eager to expand their practices
in order to make them more effective
rather than clinging
ardently to something that
perhaps is incomplete or that doesn't work
for certain individuals.
So I think they would appreciate
that feedback as would I.
So, as I mentioned before,
most of these therapies
are done in conjunction
with a skilled often one would
hope credentialed clinician.
There are many people however,
that don't have access to that
or who are working through stuff.
They have things in their past
that are very uncomfortable to them.
And I'm aware that many people are working
through those things.
Through journaling, through
talking to a friend,
through any number of different
sort of non-traditional approaches.
One thing that really
pertains to everybody
who's working through fear
and trauma of any kind
is the importance of social connection
as it relates to the chemical systems
and the neural circuits
associated with fear and trauma.
And this is a emerging
literature in Neuroscience
that is really a beautiful one because
it's a very conserved biology.
We see it, believe it or not
in flies and fruit flies,
a commonly used model system.
In mice and indeed in humans as well.
And this is the work of David
Anderson's group at Caltech,
again, of Dr. Ressler's
group at Harvard Medical
and elsewhere, of course.
And this is the work as
it relates to Tachykinin.
Tachykinin is a very interesting
molecule in our brain
and it turns out the
Tachykinin is activated
in neurons of what's
called the central amygdala
and some nearby structures.
So really smack dab within the
middle of this threat reflex.
Very soon after some traumatic
or fear inducing event occurs.
And it actually sets in motion
a number of other things
including changes in gene
expression and potentiation
meaning long-term potentiation,
activation of an NMDA receptors and so on.
In the circuits that
reinforce that fearful
or traumatic experience.
Now what's interesting about Tachykinin
is also that it's been shown to lead
to low to moderate levels of anxiety
and even kind of aggression, irritability.
Tachykinin levels are further
increased by social isolation.
And that social isolation is
oftentimes what can exacerbate
pre-existing traumas or fearful events.
And in a kind of
beautiful symmetry to that
kind of dark and depressing story,
social connection with
people that we trust.
And it doesn't have to be
direct physical contact
but just social connection
conversing with,
sharing a meal with,
it could be physical touch
if that's appropriate.
Those sorts of connections
actually serve to reduce
the effectiveness or even
the levels of Tachykinin.
So the important point here is that
trauma is traumatic in and of itself.
Fearful events are hard
in and of themselves.
And if people are working through them
either through clinical work
or through individual work.
It is important and in ideally
one would still be trying
to access social connection
outside of that specific
work-related to the trauma.
Now it doesn't necessarily
have to be outside of that.
For instance, if you
have a good relationship
with a clinician or therapist
to the point where there's real trust
and you feel a social
connection with them, wonderful.
But for many people,
they have a more
transactional relationship
to the EMDR practitioner
or to their therapist,
or they're working through
things on their own.
And it's really important to understand
that regular social connection,
trusting social connection of any kind
is going to be very
beneficial for that process.
And so this is not the
kind of just hand-wavy,
a new agey stuff like,
"Oh, you know you need social connection."
There's a actual neurochemical
basis for social isolation
that has an amplifying
effect on fear and trauma.
And there is a neurochemical
basis for the relief
from fear and trauma and isolation.
And in the ideal circumstance,
one is working through
these traumas and fears
very intensely in a very dedicated way.
But then is also engaging
in the sorts of social interactions
that are going to diminish
the amount of Tachykinin
and going to suppress those very circuits
that would otherwise be amplified.
So next I'd like to talk
about some really interesting
and almost kind of eerie
scientific findings.
And that's the transgenerational
passage of trauma
or predisposition to fear and trauma.
This is a scientific
literature that's been debated
many times over the last
really 50 plus years.
But in more recent
studies have really proven
that we as humans have
the capacity to inherit
a predisposition to trauma or fear.
Now that doesn't necessarily
mean that we will become
traumatized or experience extreme fear
just because our parents or
grandparents experienced that.
It's a predisposition, it's a bias.
Let me explain the
papers that focus on this
for a little bit.
And then we'll talk about what
this means for each of us.
One of the most important
papers in this area
comes to us from someone
I mentioned earlier,
Dr. Kerry Ressler at Harvard.
And the title of the paper is,
Association of FKBP5
polymorphisms and childhood abuse
with risk of posttraumatic
stress disorder symptoms
in adults.
And there are other papers as well.
Another one from the Ressler's Lab,
first author, Brian Dias, D-I-A-S.
Parental olfactory experience
influences behavior
and neural structure in
subsequent generations.
I'm going to summarize these
papers and their general contour
and papers related to them.
Although, feel free to look up
the papers I just described.
We will provide a link
to them in the caption
if you'd like to go further.
But basically these explorations involve
looking at the histories
of human individuals
who had trauma or abuse of
some kind in their childhood.
And then looking at the likelihood of fear
and PTSD type symptomology
in their offspring.
And essentially what they
identified is that indeed,
if you had a parent and there does seem
to be a kind of a bias
toward an effect where
if the father had abuse
and it's severe abuse
or moderate abuse.
That abuse causes a
change in his genetics,
in his sperm that can be
passed on to offspring
such that the offspring
have a lower threshold
to develop trauma or extreme fear
to certain types of events.
Now what's important to point
out is that predisposition
or bias is not necessarily
to the same sorts of events.
It's not that the abuse itself gets passed
from one generation to the
next it's a predisposition.
And the title of that paper mentioned,
FKB5, excuse me, FKBP5 polymorphisms.
And the FKBP5 polymorphisms
maps to a location
in the genome that's associated
with the so-called glucocorticoid system
with cortisol release.
So the predisposition
that one might inherit
from having a parent father or mother
but stronger tendency to
inherit it from the father.
Who experienced abuse is one in which
the glucocorticoid system,
the cortisol system,
and that HPA axis that
we talked about before
the hypothalamic-pituitary-adrenal
axis is sensitized
or reactive in a way that
sets a lower threshold
to become traumatized or very afraid
of certain types of events.
But it's not unique to
the specific type of abuse
that the parent experienced.
Now, this is really, really important
because a lot of times out there
I will hear that there's passage
or transgenerational
passage of actual trauma,
the specific trauma.
Now that could be through
narrative telling,
if somebody is exposed
to a lot of narrative
about their parents' trauma
in one form or another.
It may be that they start to internalize
some of that trauma.
And there could be because we
obviously can't rule it out.
There could be some other signatures
of prior specific traumas they
get passed on to offspring.
But more likely and
certainly what these data
about these polymorphisms point to
is that what gets passed
on is a propensity
for the threat reflex to
get activated and attached
to a wider variety or to
less intense types of inputs
and experiences.
And the important point
to take away from this
is that it's not some magical, mysterious,
and mystical thing
that's being transplanted
from parent to child.
It's a gene or it's a
modification in a set of genes
that gives a heightened
level of responsivity
to fearful type events.
Or even a high level of responsivity
such that things that
wouldn't be fear inducing
or trauma inducing to certain individuals
can trigger fear and
trauma in these children
that inherit this particular gene.
Now that doesn't necessarily
mean that they are faded
to forever be traumatized or live in fear.
It's simply not the case.
It's just a genetic predisposition
regardless of whether or not
you had a parent or parents
that were traumatized or not.
There's no evidence, at
least as far as I'm aware
that the treatments for trauma
should be any different.
As far as I know there
aren't gene therapies
currently aimed at these
particular variants,
like FKBP5 and so forth that
could reverse those particular
genetic underpinnings of
the trauma predisposition.
So this transgenerational
passage of trauma,
I think is extremely
interesting in large part
because it brings us back to this idea
that the threat reflux is part
of a larger sensory system.
You know, normally we think
of seeing as a sensory system
or hearing as a sensory system.
But the threat detection
and threat learning system,
the fear learning system is
in many ways a sensory system.
It's just a sensory system
that is very generic
in its response.
That generic response again is good
because it allows for flexibility
but it's bad because it
reduces specificity, right?
We can essentially become fearful
or traumatized by anything if
the circuit gets activated.
And these particular children
inherit a predisposition
for more things and less intense
things to traumatize them.
In a few minutes, we are going to discuss
some of the behavioral treatments
including some really
new exciting protocols
for dealing with fear and trauma.
But for a few minutes,
I'd like to discuss some
of the drug treatments
that are starting to emerge
as potential therapeutics
in particular for PTSD.
The two drug treatments
I'd like to focus on
are Ketamine-Assisted Psychotherapy,
and MDMA-Assisted Psychotherapy.
Currently Ketamine-Assisted
Psychotherapy is legal.
It is approved, provided it is prescribed
by a board certified physician
in the United States.
I'm not certain about
other areas of the world.
MDMA also sometimes called Ecstasy therapy
is in clinical trials in the U S,
it is still an illegal
drug to possess or to sell.
So I want to be very clear about that.
However, MDMA is being explored
as a potential therapeutic for PTSD
and other forms of trauma.
And of course, Ketamine and MDMA
are also both being explored
for chronic depression,
eating disorders and a number of other
psychiatric disorders.
But for the moment I would
just like to touch on
Ketamine and MDMA as they relate
to the fear circuitry and trauma circuitry
that we've described in the
early part of the episode
and throughout the episode.
Because I think that in
viewing them through that lens,
we can gain some additional insight
into how they might be
providing the sorts of relief
that some of the early clinical studies
are starting to point to.
Ketamine is a dissociative anesthetic.
That's right.
It's a dissociative anesthetic.
It's main function is to
create a state of dissociation.
And I've never taken ketamine personally
so I can't describe the experience of it.
But a colleague of mine in psychiatry
shared their experience with
a patient's experience of it
as making that patient feel as if,
"They were getting out of
the cockpit of a plane,
but that they were observing
themselves doing it."
And this was of course,
during a approved therapeutic session
that they were doing this
and they were in some sort
of intense visualization
about a traumatic experience.
They were describing some
of their depressive symptoms
as well as the trauma.
And their narrative that
they basically created
or took away from this.
And that was relayed
to me was one in which
the patient felt like they
were in their own body
but they were also viewing
their own body from the outside.
So dissociative, in other words.
Again, I've never had this experience.
Some of you may have with
Ketamine or through other means.
But we might want to just
take a moment and think about
what Ketamine actually does
and what dissociation actually does
at the level of neurocircuits?
And for that, we can look to
this really beautiful paper
that was published by my colleagues,
Karl Deisseroth in psychiatry,
Robert Malenka, also in
psychiatry, Liqun Luo,
also at Stanford.
They paired up or teamed
up rather to explore
how systemic Ketamine adjust
circuitries in the brain.
And what they discovered was that
it changes the rhythm of cortical activity
in certain layers of the cortex.
The cortex is like a layered sandwich.
The cortex of course, being
the outside of the brain.
And there was a particular rhythm
a one to three hertz rhythm.
One to three hertz just
means a particular frequency
of electrical activity.
In this case,
in these layer 5 neurons
of Retrosplenial cortex.
So you don't need to know much
about Retrosplenial cortex
or a one to three hertz rhythms.
I think the important thing
to just take away from this
is that there is now starting
to be an understanding
of how drugs like Ketamine work
to create this subjective
experience that this patient
and other patients
describe as dissociation.
You know, dissociation in its essence
is really about not
feeling what's happening.
It's about viewing what's happening
from a different perspective
than what normally
one would view that experience from.
And so if we add a plug that
general notion of dissociation
and Ketamine induced
association into the circuit
that we talked about before,
where we have this threat
reflex involving the amygdala.
These outputs for freezing or
for reward and the accumbens.
And we've got this prefrontal
narrative coming down
as top-down processing.
It brings us right to that
prefrontal cortical input
to the threat system and that narrative.
What seems to be the case
in my review of the paper
I just described,
plus a review on how
Ketamine-assisted trauma relief
might work is that it
somehow allows the patient,
the individual to recount
their trauma while feeling
either none or a very different
set of emotional experiences
that they experienced in the actual trauma
or fearful experience.
So it's a remapping of new onto old.
New meaning new feelings onto
old feelings while staying
in the exact same narrative.
So it's a little bit
like EMDR of suppressing
the threat reflex but it seems
to bring in a replacement
of previous emotional
experiences and sensations
in the body with new ones.
And so in that way we can sort of view
or we can try and view
Ketamine-Assisted Psychotherapy
for the treatment of
trauma as bringing together
the three elements that
we talked about before.
You want to diminish the intensity,
the potency of the old
original trauma experience
or fear experience.
So that seems to be accomplished
through this dissociation
and maybe through the kind
of anesthetic component.
So it's a reduction in pain
in the body, a dissociation,
a kind of observing of the self
that leads to the extinction
of the trauma and the fear.
But then there also
seems to be an automatic
or kind of built in a
relearning of a new narrative,
a new set of experiences
which is the next step
that we described earlier.
So it's an intriguing therapy.
It's one that's really catching on
and there are many, many
clinics around the U S
that are now doing it.
Whether or not it turns out
to be the ultimate treatment
for trauma and for fear isn't clear.
My colleagues in psychiatry
tell me that that's unlikely,
although it does seem to be beneficial
for a number of people.
Especially people that
are experiencing trauma
or have existing traumas and fear
that are coupled with depressive symptoms.
Because the data on
Ketamine and depression
seems to be quite strong.
So now let's talk about MDMA.
MDMA also sometimes
called Ecstasy or Molly
in its recreational form is
a powerful synthetic drug
that at least as far as we know,
creates a state in the brain
and body that is unlike
any other chemical state
in the brain and body
that's normally experienced.
What do I mean by that?
Well, we have several
Neuromodulator systems in our body.
Neuromodulators are chemicals
that change the likelihood
that certain neural
circuits will be active.
Meaning they can make it very
likely that certain circuits
will be active and make it
very unlikely that other
neural circuits will be active.
Good examples of neuromodulators
are dopamine, serotonin,
acetylcholine, norepinephrine.
These tend to work on different systems
in the brain and body but
they tend to be activated
more or less in parallel, right?
You can have Dopamine
released in your brain
and also Norepinephrine.
You can have Serotonin
released in your brain
and also Acetylcholine.
So it's not an all or none kind of thing,
but the degrees to which
these things are activated
tends to vary.
And there is a little bit
of a seesaw type phenomenon
with Dopamine and Serotonin.
Dopamine most commonly
associated with activating
neurocircuits related to
motivation, craving, and reward.
And Serotonin more typically activated
in response to situations or conditions
in which we are very happy
and content with what we have.
So Dopamine is more about
pursuing and seeking.
Serotonin is more about kind
of pleasure and satisfaction
with resources that we have
in our immediate sphere.
They don't tend to...
Serotonin doesn't tend to
place the brain and body
into a mode of action
quite as much as Dopamine
does, more or less.
MDMA is a unique compound in that it leads
to very large increases
in the amount of both
Dopamine and Serotonin in the
brain and body simultaneously.
And that's a unique circumstance
that is just simply not
seen under normal conditions.
From a subjective standpoint,
people under the influence of MDMA
in the therapeutic setting,
tend to report immense feelings
of connection or resonance
with people or even things
with music, with objects.
Certainly if it's being
done in conjunction
with a family member or a
partner or with a therapist,
they will feel extremely
connected to that person.
They'll feel a very close
understanding and association.
Oftentimes that goes beyond words.
There is a chemical reason for that.
It turns out that MDMA causes
massive release of oxytocin.
This neuropeptide that's
associated with pair bonding
and with bonding generally.
The oxytocin system and
the Serotonin system
are closely linked to one
another in the brain and body.
And they tend to be co-released
often at the same times
and by the same sorts of events.
So MDMA is one mechanism by
which oxytocin is released
in these massive amounts.
And I should just relay some
of the levels of oxytocin
because they're really quite striking,
gives a kind of a more vivid
picture of why it is the MDMA
would make people feel so
associated in a positive way
with the various things
that are happening them
while they're under the
influence of the drug.
So the paper related to this
that I'd like to highlight
is in the journal
Psychoneuroendocrinology.
The title of the paper is
Plasma oxytocin concentrations
following MDMA or intranasal
oxytocin in humans.
And just remarkably MDMA
increased plasma oxytocin levels
to 83.7, this is an average,
83.7 picograms per milliliter.
About 90 to 120 minutes
into the MDMA session
compared to a typical level of 18.6.
So this is a massive increase in oxytocin.
And I think that massive
increase in oxytocin
is part of the reason
why people have these
feelings of close
resonance and association.
Now, the Dopamine increases
are generally what lead
to the feelings of euphoria
inside of the MDMA session.
And then the Serotonin
increases it is thought
are what lead to the feelings
of safety and comfort.
So again, a very unusual chemical cocktail
that would never be seen at
least not at this amplitude
under any normal conditions
outside of an MDMA
clinical psychotherapeutic session.
Why would this state of mind
and body be potentially useful
for the treatment of trauma?
Well, indeed it is revealing
itself to be useful
for the treatment of trauma.
Again, these are legal clinical trials
where people are doing
this and discovering this.
What it seems to allow
is a very fast relearning
or new associations to be tacked on
to the previously traumatic experience.
So again, it brings us
back to the same model
of how people extinguish fears and traumas
and replace them with new experiences
when there is no drug treatment involved.
There needs to be a diminishing
of the old experience,
meaning an extinction
and then a relearning
of a new narrative.
What the chemical [indistinct] of MDMA
seems to be doing is
creating an opportunity
for all that to happen very fast
without the need for many
repetitions of the original trauma
and reliving of the original trauma.
Probably because the reliving of it inside
of one of these MDMA sessions
is very acute, very intense,
plus it seems to be
offering the opportunity
to extinguish and rewrite in or write in
a new narrative associated
with that trauma
very quickly as well.
So what this means is
that treatments like MDMA
that are under investigation
in these clinical trials
are unlikely to be magic
potions, if you will,
that allow access to a particular process
that would otherwise not be accessible.
It's more that the
typical process of trauma
and fear reduction that's
carried out in things like
prolonged exposure, cognitive processing,
cognitive behavioral therapy
seems to be compacted
into a much shorter session.
And that session is performed
at a much higher intensity.
Higher intensity because
the chemical [indistinct]
of the brain is completely different.
I mean, the experience of
MDMA is one in which people
have a very heightened sense of euphoria,
very heightened sense of connection.
So those positive experiences
are essentially primed
to be written in and over
the traumatic experience
and because of the high levels
of Serotonin in the system
and probably oxytocin as well,
there's a safety that's
written into the situation
that allows people to lean
into perhaps narratives
or components of narratives
that they would otherwise
be holding back from.
So these are powerful compounds,
and I think the future of
MDMA-assisted psychotherapy
for a trauma in particular
is holding great promise.
As of now, meaning at
the time of the recording
of this podcast.
Again, I want to reiterate
that these are clinical trials
are being done legally.
These drugs are still
illegal to possess or sell
outside of clinical trials.
Doing this sort of thing is punishable.
But it does seem that the FDA
and some of the related bodies
that control these sorts of things
are eyes open to this stuff.
And I think it's very likely
in the next few years,
things like MDMA and
certainly Ketamine has already
in widespread use within
the psychiatric community.
And I think we're going to
be seeing a lot more of that.
One thing we have not touched on yet
is how do you know if you're traumatized?
How do you know if you have chronic fear
or a debilitating fear?
You know, much of the
psychiatric community
focuses on how many other
problems people might have.
Trouble sleeping, trouble eating,
trouble maintaining
quality work, or schoolwork
and so forth.
And all of those are
certainly very valid criteria
and necessary criteria for determining
whether or not somebody meets
a clinical diagnosis or not.
But there's a biological component
that I think we can all
assess for ourselves.
And that's one of
interoceptive versus
exteroception balance.
And that sounds confusing,
but it's actually really
easy to understand.
We can focus our perception
on the external world,
events going on around us,
beyond the confines of our skin
or within the confines of our skin.
A focus and a perception
on the external world
is what's called exteroception
and a focus on what's happening
inside us is interoception.
And we have the capacity
to build mental appraisal
into that, right?
I can for instance, stop
for a moment and assess
how my stomach feels, how hungry I feel,
how quick my heart is beating.
Some people by the way
are much better at sensing
whether or not their heart is
beating at a particular rate
and others, not so much.
Some people can actually
count their heartbeats without
having to take their
pulse by placing pressure
on their wrist or their neck.
Some people can't.
In other words, some people have very high
interoceptive awareness
and other people less so.
This whole business of fear
and trauma relates to taking
external experiences and
funneling those experiences
into this thing that I'm
calling a threat reflux
or the fear circuitry.
A recent paper published
in the journal Science.
So absolutely spectacular
journal, science, nature and cell
being the apex journals
of scientific publishing.
Gets at this issue of where in our mind
and how do we assess whether or not
what we are feeling
internally is reasonable
given what's going on externally.
And it's a really fascinating study.
I'm just going to highlight
a little bit of it for you
and then I'll touch on some
of the relevant aspects
and how that can be
adopted into a practice
to assess and reduce fear and anxiety.
The title of this paper
published just a few weeks ago
in Science is,
Fear balance is maintained
by bodily feedback
to the insular cortex in mice.
We've not talked too
much about the insular,
also called the insular cortex.
This is a brain area
that my lab has worked on
and other labs have worked on.
It's a brain area that has within it
a map of our internal
interoceptive landscape.
It's a map of our internal
bodily sensations.
And it's a really interesting structure.
So the way this study
was carried out is that
subjects were taught or conditioned
to a particular danger signal
through repeated presentation
of a sound with a foot shock.
So there's a sound and
there's a foot shock.
And as you know, from
our earlier discussion
about Pavlovian learning,
conditions stimulate,
an unconditioned stimulate.
Eventually the sound alone comes
to evoke the fear response.
And that's just classic,
classical conditioning.
The insular is this brain
area that's associated
with determining whether or
not one's internal sensations,
gut, heart, lungs, et cetera,
are reasonable or not given
the external circumstances.
It can even measure or is associated with
our understanding of what are
called arterial baroreceptors.
These are blood pressure sensors.
So believe or not, when you
know your pulse rate increases
or you feel like you're stressed out,
your arterial baroreceptors
are sending a signal
to your insular cortex and
your insular cortex is saying,
wow, like I'm really stressed out,
my blood pressure is up, right?
You don't actually have to
measure your blood pressure
with a cuff, your insular
is doing it for you.
It's not getting a quantitative readout,
but it's getting a qualitative readout.
The main effect of inhibiting
or reducing the activity
of the insular was that the intensity
of an outside world
experience led to a range
of different internal effects.
In other words, for most people
a mild shock would induce a
mild increase in heart rate,
a mild increase in blood pressure.
Whereas an intense shock to the skin
would lead to a big increase in heart rate
and a big increase in blood pressure.
Turns out the insular is
important for establishing
that match of intensity.
And when the insular is inhibited,
what ends up happening
is that a mild shock
can create a big increase
in blood pressure.
And that can be maintained
such that anything
that's paired with that shock like a bell,
or a tone would lead to a big
increase in blood pressure.
You've probably seen examples
of this in the real world.
Maybe this is even you.
Some people are very jumpy in response
to just even small changes
in their environment.
So if somebody is working and you walk in
and you say, "Hello."
And they'll go, they're jumpy.
They have a low threshold to a
big anxiety or fear response.
Other people are really calm.
I recall my bulldog,
unfortunately passed away,
but before he passed away,
if you walked in the room
and he said, "Hey, Costello."
He might turn his eyes in your direction.
He had a very high threshold to respond.
He was pretty low anxiety animal.
A lot of people are like that.
You'd come up behind
someone you say, "Hello."
And they just turn around real slow,
or they might just turn
around at normal speeds
and say, "Hello."
Whereas other people
jump out of their seat.
The insular seems to be
involved in calibrating
how big or how high amplitude
a given physiological response is.
So it's pairing the internal landscape
with the external world.
And this might seem
like just a mechanistic,
but non-actionable point.
But what you'll see from the next study
that I'm going to describe
is that recalibrating
the relationship between outside events
and internal responses,
which is the job of the
insular is actually something
that's under our control.
And through a very simple,
very short protocol,
we can actually recalibrate
that system so much so
that we can potentially reduce the amount
of fear and trauma that we experience,
in response to a memory
or to a real event.
And the entire process
can occur very quickly.
So I'm really excited to tell
you about this next study
for a number of reasons.
First of all, it's extremely recent.
Second of all, it's very well grounded
in our current understanding
of the mechanisms of stress,
trauma and PTSD and unlearning
of stress, trauma and PTSD.
And third, it points to
a actionable protocol
that while certainly is
not the only approach
that I think people could or should take
for fear, trauma and PTSD.
Is one that I think we are
going to see implemented
into the clinical setting very soon
if it's not happening already.
Now, there's a fourth reason
I'm very interested in it,
which is that my lab works on stress,
stress-relief and tools for managing sleep
and improving focus, et cetera.
And one of the hallmarks of the studies
we've been doing lately is
very brief five minute a day
interventions of the sort that was used
in this particular study.
Although I should emphasize,
I had nothing to do with
this particular study.
Now this particular study was carried out
in an animal model in mice.
The work in my laboratory
focuses on human subjects.
But the similarities of the stress system
at least at the level that
it was explored in this study
I think have great relevance
maybe even direct relevance to humans.
So the title of this study is,
Repeated exposure with
short-term behavioral stress
resolves pre-existing stress-induced
depressive-like behavior in mice.
Again, this study was in mice.
And basically what they did
is they stressed out mice,
got them depressed, and you
actually can do that in a mouse
using a restraint protocol.
And that's a long lasting
restraint protocol,
a 15 minutes or more.
Mice Don't like it,
you do it often enough.
They stop working so hard in their life,
in their mouse life to
gain food, to gain mates.
They show depressive symptoms
in a number of levels.
They show elevated glucocorticoids.
You see the same thing in humans, Okay?
Chronic stress in humans
lasting weeks or more
does the same exact thing.
So again, a very close match here in terms
of mechanism overall.
And then what they did was a
very counterintuitive thing.
Rather than give these
animals stress relief
at the level of reducing their anxiety
with Benzodiazepines,
or giving them a nice
little mouse vacation,
or enriched environment.
Things that have been done
in a lot of previous studies.
What they did is they subjected
them to five minutes a day
of intense stress, but
only five minutes a day.
And what they found was miraculously,
but also very convincingly.
Daily short bouts of intense
stress actually undid,
reversed the effects of chronic stress.
And it did this at the
level of glucocorticoids,
of hormones, of neurotransmitters
and a number of other
different mechanisms.
Now, I find this very exciting
for a number of reasons
but in particular, because my
laboratory in collaboration
with David Spiegel laboratory,
our associate chair of
psychiatry at Stanford.
Been exploring how five minute
a day respiration protocols
can alleviate stress.
And while those data
are not yet published,
they are at the stage
where I'm comfortable
talking about them.
And we are seeing some very impressive
and significant effects
on stress reduction
not just from respiration
protocols that allow people
to calm themselves but
also respiration protocols
that bring people into a heightened state
of autonomic sympathetic
arousal, AKA stress.
As my colleague, Dr. David Spiegel,
he's an MD psychiatrist and PhD.
Likes to say, "When it comes
to trauma, anxiety and PTSD,
and the treatment of
trauma, anxiety, and PTSD,
it's not just the state that
you are in or that you go into.
It's how you got there and
whether or not you had anything
to do with it."
And this brings us right back to those
top-down mechanisms and the narrative
around what we are
experiencing internally.
So let's zoom out and I'll
explain how this works
and what to do about it.
We have this brain structure
called the insular.
We talked about the
insular a few minutes ago.
The insular is calibrating
how we feel internally
versus what's going on externally.
It's involved in setting whether or not
what we are feeling is appropriate
given what's happening.
We have a system that can
generate threat responses.
And in the case of trauma,
PTSD, and extreme stress,
chronic stress, that system gets ramped up
so that it takes very little,
maybe even just a memory
or maybe even an association
that we're not even aware of,
our location trigger something,
we're not even aware of it.
And we start experiencing
that symptomology.
How do we recalibrate the system?
Well, most of the approaches
that are out there
involving drug treatments,
typical drug treatments would
involve suppressing the level
of internal arousal.
Just trying to bring that down.
Now, some of those drug treatments work.
But oftentimes they don't.
And if you think about it,
it's probably not
surprising that they don't
because by taking a drug
that just lowers your anxiety overall
you're creating a different
sort of miscalibration
of the system.
So what we've been doing in human subjects
is having them do either breathing
protocols that calm them,
and I'll explain what that is in a moment,
or doing breathing protocols that increase
their level of autonomic arousal
and seeing how that impacts their response
to stress overall not just
during that particular
breathing protocol.
So the calming protocol that we use
involves these physiological size.
I've talked about these
previously on the podcast
and elsewhere but if you
just need a reminder,
if you haven't heard about it.
There's a pattern of breathing
that we all do in sleep.
When our carbon dioxide
levels in our bloodstream
get too high.
And we do this when we get claustrophobic,
meaning we do it reflexively.
And that's a double
inhale through the nose
followed by a long exhale.
So it's,
[Andrew breathing]
And yes, the inhales
should be through the nose
and yes, the exhales should be done
through the mouth, ideally.
So it's a big filling of the
lungs through two breaths
back to back.
Inhales.
[Andrew breathing]
Even if you could only
sneak in a little air
on that second one,
no talking to if you're
going to do it right.
And then a long exhale,
which allows you to offload
a lot of carbon dioxide
in the exhale.
And we have people doing that in real time
anytime they experienced stress
but the particular breathing protocol
that we've been giving human subjects
is for them to do the repeated...
What we call cyclic sign.
So double inhale, exhale,
double inhale, exhale,
double inhale, exhale
repeatedly for five minutes.
Which is actually a pretty
long time to repeat that.
But you can do it pretty
slowly and people report
and the data point to the
fact that it's very calming.
People feel more relaxed afterwards
and that relaxation wicks
out into other aspects
of their life.
Now, we did not look at stress
and trauma in that condition.
We also have another
condition where people do
what's called cyclic hyperventilation,
which is very different and
creates a very different
internal state and is somewhat stressful.
It's five minutes a day of stress
much like the study that I just described.
And involves basically doing this,
what I'll do in a moment for five minutes
which is hyperventilating.
Which is,
[Andrew breathing]
But not continuously for the five minutes
because many people would pass out
or feel extremely uncomfortable.
It involves inhale,
exhale, inhale, exhale,
very deep inhale through the
nose, exhale through the mouth.
And then every 25 or 30 breaths
or so doing a full exhale
and holding one's breath, lungs empty
for about 25, maybe 30,
maybe even 60 seconds.
And then continuing
until five minutes is up.
Subjects report and our
data indicate that people
feel a heightened level
of autonomic arousal.
In fact, I can feel it right now
even from a very brief
cyclic hyperventilation about
I just did.
You feel a heating up, you feel a...
Some people will perspire,
some people get wide-eyed,
some people feel agitated.
That's Adrenaline being
released into your system.
Now I'm not suggesting
everyone run out and do this.
And if you have a
predisposition to panic attack
or anxiety attacks please
don't do this because
it is very stimulating
and can trigger those sorts of attacks.
But this five minute a day protocol
of cyclic hyperventilation
does lead to big increases
in autonomic arousal.
So it's "Stressful" but to bring us back
to my colleague, David Spiegel's quote.
It really was him that said it, not me.
It's not just about the
state that you're in.
It's about the state that
you're in plus how you got there
and whether or not you
directed entry into that state.
And that point one directs
their own entry into a state
deliberately is really key.
And I think has an important
implications for whether or not
their stress relief and fear
relief and trauma relief
from bringing oneself into a state
of increased autonomic arousal.
Why?
Because of the way that that
fear and trauma circuitry
is organized.
If you recall, it's got these components
of how external events can trigger
an internal stress
response and fear response
and trauma response.
But there's that top-down
prefrontal component
that can inhibit certain
aspects of that fear
and threat circuitry.
Now, earlier we were talking about
that prefrontal circuit being
engaged through narrative,
through self-directed
deliberate narrative.
It's the person deliberately
retelling the story?
Here we're talking about
a deliberate reactivation
of the sensations in the body.
So where I think this is all going,
meaning where my laboratory
and the Spiegel laboratory
and other laboratories
out there are taking this.
Is you can imagine a very
brief five minutes a day,
two weeks was the time that they did this
for five minutes a day for two weeks.
Intervention in which people,
with the support of a
clinician we would hope,
would deliberately induce
a physiological state
that's very stressful, right?
Not shying away from the stress response
but increasing their own
stress response deliberately.
And maybe in conjunction
with recounting the traumatic
or fearful circumstance.
This is far and away different
than the kind of state of mind and body
that would come about
in a Ketamine-assisted trauma
induced psychotherapy session,
or a MDMA-assisted trauma
psychotherapy session.
Or in a purely narrative
based psychotherapy session
aimed at alleviating fear or trauma.
The reason I like these sorts
of interventions is that,
A, they are very low cost
or even zero cost, right?
One you could imagine
doing this while journaling
or while recounting a
particular experience.
Again, they're very
compact five minutes a day
for two weeks is what was done
in this particular mouse study.
We don't know if that translates directly
to the human study or not.
What was interesting is that if they use
the longer daily bouts of
stress, like 15 minutes a day,
that actually exacerbated the trauma
and exacerbated the fear.
So one has to be very careful.
Stress and deliberate entry into stress
and self stressing are very potent tools.
They're very sharp blades
that it does appear
or it's likely can help
alleviate trauma and fear.
But how long to do this?
Exactly what the protocol should be
is still something that
needs to be cultivated.
I know there are going to
be people out there that
that nonetheless are going
to want to experiment
with some of this.
I will say that I do not think it matters
how one gets into that stressed state
provided it as self-directed
and that therefore could be cold shower.
It could be ice bath.
It could be anything
that induces an acute,
meaning a sudden onset of
Adrenaline and is self-directed
that's really the key feature here.
So I'm very excited about these data
both the five minute intervention data
from the animal study.
The work that's ongoing in my laboratory
and Dr. Spiegel's laboratory,
and the work that's being
done on the insular.
Because I think what
we're starting to see now
is a picture of fear and trauma and PTSD
that has the sensory component,
what's happening in the world around us.
This internal interoceptive component,
how appropriate are the signals
that are occurring in my body?
I mean, let's face it.
If you almost get hit by
a car and your heart rate
is 140 beats per second.
And that lasts for a little
while and you're stressed out,
you don't get the best night's
sleep, that's pretty normal.
That means you have a healthy fear system.
If that persists and you're
dealing with a lot of issues
a week later, six weeks
later, two years later.
Then it's moved into the
realm of trauma and PTSD.
So we need to always
be taking into account
the different components of the circuitry.
I do think that deliberate
self-directed entry
into these short bouts of stress
is a very promising approach.
And it's one that if people
are going to experiment
I just again, want to
caution people with anxiety
or panic disorders be very
cautious, probably don't do it.
Ideally you would do this
in conjunction with support
from a clinician.
But I'm also aware that there
are a lot of people out there
that are dealing with trauma
and dealing with post-traumatic
stress of various kinds.
And that they're desperate for various
self directed intervention approaches.
So just very briefly, I want to
touch on some of the lifestyle
and supplementation factors
that can impact things
like fear and trauma and
getting over fear and trauma.
To make a long story short.
There are many things that
we all can and should do
to support our overall
mental and physical health.
And these are the foundational elements
of quality nutrition.
What that means to you?
Quality sleep on a regular basis,
ample sleep on a regular basis.
We have an episode on how
to master sleep in bed.
We have four episodes that
you can go to hubermanlab.com
or elsewhere and scroll down
and you can find those episodes
in order to get your sleep
really dialed in as they say.
If you're sleeping regularly
and for sufficient duration,
all of the systems of your fear circuitry
are going to function better.
Mainly because the
autonomic nervous system
becomes very dysregulated
when we are not getting good
sleep on a regular basis.
Dysregulated means that out of nowhere
we can have a higher propensity
to have sympathetic activation
or we can feel really tired and wired.
That seesaw that I described
earlier of alertness
and calmness of sympathetic
and parasympathetic.
In that analogy we can imagine that seesaw
has a hinge and that hinge
can neither be too tight
nor too loose.
If it's too tight,
you can get locked into
chronic activation of alertness
or chronic fatigue.
If it's too loose, you're
bouncing all over the place
and you might be [indistinct]
tired and wired one moment
and then really hyper alert.
Sleep resets that balance
and resets that hinge
to the appropriate tightness, if you will.
So that all these circuits
and not just the circuits related to fear
but also the circuits
related to cognition,
clear thinking to be able to spell out
very clear detailed narratives,
to feel like you are in control.
You are deliberately bringing
yourself into these protocols
if that's what you intend to use.
All of that functions much better
when you're sleeping well and eating well.
We talked about social connection.
Those are all indirect
supports of trauma relief
and of getting over fear
but they are essentia, okay?
I think of them sort of like the tide.
When the tide is high enough
a boat can leave harbor.
And if the tide is not high enough,
then that boat is going
to be stranded on shore.
And in this analogy,
the boat stranded on shore is your attempt
or anybody's attempt to try
and work through something.
Very hard to do when we're sleep deprived,
very hard to do when we're not fed enough
or fed the proper foods for you.
And that's a highly individual thing.
And social connection as
we talked about earlier,
creates a general sense
of support for the ability
to move through things.
But also chemical support at the level
of suppressing Tachykinin, okay?
So those foundational
elements are absolutely key,
but they are indirect.
I just want to briefly
mention a few of the things
that some people find great benefit from
in the supplementation realm
as it relates to anxiety,
stress, fear and PTSD.
But I want to point out that again,
these are somewhat
indirect in their support
and most of them focus on
reducing anxiety overall.
The two that I want to focus
on are two that I've never
talked about on this podcast before
because I've done
podcasts before on stress
and managing stress in
the kind of shorter term.
So we've talked about Ashwagandha
in a previous podcast,
check out the podcast on stress,
if you're interested in
how that might be relevant
as well as other tools.
But the two are interesting ones.
The first one is Saffron of all things.
But there are 12 studies,
believe it or not.
That orally ingested
Saffron at 30 milligrams
seems to be a reliable
dose for reducing anxiety
on the standard inventories.
The Hamilton Anxiety Rating Scale,
for those of you that want to know.
And these are significant effects.
And these were carried out in
both male and female subjects.
Here I'm only referring to human studies.
Several of these were
double-blind studies.
There's a meta analysis
of the positive effects.
Meaning anxiolytic affects,
anxiety reducing effects that
is of things like Saffron.
Definitely have to check with your doctor
and make sure it's right for you.
But they're fairly impressive effects
when you really think about it
given that these are legal
over the counter substances.
Again, check with a doctor.
The other one is a Inositol.
Inositol has been shown to
create a very notable decrease
in anxiety symptoms.
It's a fairly high dose that's
used but believe it or not,
the potency of this
effect is on par with many
of the prescription antidepressants.
That's pretty impressive.
These studies again are
double-blind studies
that all showed decreases in anxiety.
These were done in males and females.
The age range is very broad,
which is great 18 all the way up to 64
across the studies that I at.
One of the more important things is that
the dosages are quite
high 18 grams of Inositol
taken for a full month.
And it does take some
time for these symptoms
of anxiety to be improved.
The low dose range was
about 12 grams of Inositol,
so as high as 18 as low as 12 grams.
But then again, pretty impressive results
considering that these
are over the counter
supplement compounds.
There's even some evidence,
I should just mention
that the Inositol is
also used for things like
obsessive-compulsive disorder.
We will do a full episode
on OCD in the future,
you can count on that.
But in the meantime, Inositol does seem
to have some positive effects on anxiety.
And therefore it might
provide a kind of supportive
indirect effect for people that are trying
to work through trauma and PTSD.
Now, the question is
when would you take it?
Well, by the logic of
what we spelled out today,
you probably would not want
to take it during a session
or prior to a session where
you were trying to amplify
the intensity of an
experience and the recounting
of an experience in efforts to eventually
extinguish that experience, right?
Because if you put a drug
or a compound of any kind
prescription drug or
supplement or any kind
into your system you are
essentially short-circuiting
the extinguishing effect, right?
So you could imagine doing
this outside of that session
as a way to kind of bring your system
back to baseline, perhaps.
So if you're going to
use these sorts of things
you want to think about them logically.
And this also really
points to the fact that
many of the things that
people are doing out there
to self-medicate over use of alcohol
or other substances to
try and calm themselves
because they have fear, anxiety and PTSD
are actually driving that
fear, anxiety and PTSD
deeper into their system.
Or at least is not allowing
it to relieve itself
through any attempts to recount or replay
and using these top-down
narrative circuits
or other approaches.
And the last compound I want to mention
is a particularly interesting one,
because it's neither an anxiolytic,
nor is it something that increases
overall levels of stress and alertness.
But it has some kind of MDMA
ish light contour to it.
It does not produce as far as we know,
the same mental effects or
physical effects as MDMA
by any stretch but that's...
The substance I'm referring
to rather is Kava.
Kava has been shown in eight
studies to have a very potent
effect on reducing anxiety.
But what's interesting about
kava is that kava functions
by increasing GABA,
this inhibitory
neurotransmitter in the brain.
Remember GABA is the
inhibitory neurotransmitter
that is used, that's
employed by the very neurons
in the prefrontal cortex
that serve to inhibit
the threat reflex.
So it seems to increase GABA,
but it also increases Dopamine.
And that's a somewhat unusual compound.
I'm not aware of many compounds
that simultaneously increase
GABA and increase Dopamine.
And as you recall, that
threat reflex has outputs
that tap into the Dopamine system.
Now that's a big leap
to go from a compound
that increases GABA and Dopamine
and look at a circuit spelled out on paper
in front of us and say,
"Oh, there's GABA and
Dopamine in this circuit
and therefore this is a
good compound to take."
But the effects of Kava in human studies
are pretty interesting
as it relates to anxiety,
stress, PTSD and fear.
I'm not going to summarize
all of these because
there are eight studies that I'm aware of.
But I'll just mention, again,
these are double blind studies.
So the trial design is solid.
The age ranges are anywhere from 18 to 64
which is a nice broad age range.
The number of subjects is
quite high both men and women.
No signs of hepatotoxic signal
so meaning liver toxicity,
although of course,
check with your doctor.
But what was interesting
is that after a period
of about three weeks of treatment
with anywhere from 150 milligrams
of what are called active
kava lactones, okay?
So there are dosages
that relate to that kava.
So a hundred milligrams of extract of Kava
is a kind of a reasonable
typical dose in these studies.
But that spells out to a
certain amount of Kava lactone.
So you have to kind of boil down
to what is the appropriate dosage.
And it turns out it's extremely broad.
You'll see evidence of 50 milligrams,
you'll see evidence of 300 milligrams,
is kind of all over the place.
But each of these studies
alone and together
point to the fact that
Kava does seem to produce
a very potent anxiolytic and
general kind of improvement
in depressive symptoms and
reduction in generalized anxiety
across the board.
So it's an interesting compound.
I've never actually tried
any of the compounds
I just mentioned.
Kava, Saffron or Inositol.
So I can't report on them personally.
I just know that a number
of listeners of this podcast
are interested in supplements
and legal over the counter
approaches to their biology
and psychology.
And so that's why I mentioned them.
Those were the three for which I found
the most convincing evidence
and the largest bulk of evidence.
So if you're interested in exploring those
proceed with caution but they
do seem quite interesting.
So today we've reviewed a
large amount of information
about the biology of pathways
in the brain and body
that underlie the fear response.
And they give rise to chronic fear
and in some cases to trauma and PTSD.
We also touched on a large
variety of approaches
to dealing with fear, trauma and PTSD
that currently exist in the
clinical landscape out there.
I also touch on some
of the emerging themes,
for instance, this short five minute a day
deliberate self-directed
stress of any kind
through respiration or other approaches
of increasing Adrenaline.
As an approach that might be viable,
I should emphasize might,
be viable for enhancing the speed
or the potency of
treatments to reduce fear
or eliminate trauma.
Most important I believe is to understand
and really think about
the logical structure
of the circuits that
underlie fear and PTSD.
Because in doing that
each of us, all of us,
can think about what sorts
of treatments and approaches
make the most sense for them.
I also hope that it will help people
lean into certain practices
involving re-exposure,
provided that's done in
a supportive environment.
Re-exposure to a given traumatic event
in an attempt to extinguish that.
Obviously you want to do that safely,
meaning psychologically
safely and physically safely.
There are great practitioners out there
that can help you with that work.
There are also a number
of people out there
I am certain that are
carrying certain traumas
or certain fears that they
would like to alleviate
that are not in the
extreme clinical realm.
And that's the reason why I
touched on a number of things
including some self-directed practices
that might be useful and
reasonable for them to explore.
I realize we covered a
lot of information today.
If you're enjoying and are
learning from this podcast
and you're not traumatized
by the amount of information covered,
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On this podcast episode
and in many previous podcast episodes,
I describe supplements.
While supplements aren't necessary
and perhaps aren't right for everybody
many people derive great
benefit from supplements.
It is important however,
that if you're going to use supplements
that they be a very high quality
and that you can trust that
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That's a serious issue with a
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For that reason, we partnered
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