Erasing Fears & Traumas Based on the Modern Neuroscience of Fear

- [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

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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,