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I was thinking how can we mislead our

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brain and weaken the fear memory itself

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emotional memory that underlies anxiety

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disorders is not a sort of single memory

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Trace but it is a network this changed

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our whole idea of memory

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this episode we talk about a

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groundbreaking intervention for

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treatment resistant PTSD panic disorders

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and fear in general merrell-kindit is a

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professor of Clinical Psychology and a

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pioneer of research in fear Extinction

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when I heard about this research I was

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flabbergasted that it wasn't getting

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anywhere near the press that I thought

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it should this by the way is an

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unreleased episode from approximately

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two years ago near the beginning of the

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theories of everything podcast with

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Merrell kindett forgive my nasincy as a

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podcaster as I've changed substantially

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and hopefully substantively in various

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ways since then most of them hopefully

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again positive enjoy

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we're here with Merrell Kent of the

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University of Amsterdam and she is a

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professor in fear Extinction if I'm not

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mistaken or at least that's what she

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studies so Professor can you give us an

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overview of your fear Extinction

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research

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yeah this is uh this is a long story so

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I don't know uh yeah how much time you

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have but uh I think I have to give you a

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bit of a background information

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otherwise it's really difficult to to

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understand uh the research program and

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and why we changed actually uh our

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approach from the traditional

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um approach that is taken to to tackle

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uh irrational fears for fair uh and

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anxiety disorders and also post

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traumatic stress disorder cognitive

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behavioral therapy is the most effective

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treatment and even though it is

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effective there are also many patients

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that do not profit from the treatment

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but the yeah the

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what is really a problem is the high

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relapse rate so even after successful

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treatment there are many patients that

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yeah show a relapse

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and

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um yeah this this idea of relapse after

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cognitive behavioral treatment can be

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understood by

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behavioral Neuroscience research

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so I will briefly explain that so to

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understand the mechanisms of change and

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also cognitive behavior therapy we use

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the fear conditioning Paradigm this is

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laboratory research that can be done in

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rodents but also in humans so please

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interrupt me if you don't understand me

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so cognitive behavioral therapy as far

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as I know is something like you're

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afraid of a stimulus let's let's say

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it's rats or mice then you have

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Progressive exposure over the course of

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weeks maybe even months so that is how

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far can you go to a rat can you go nine

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meters and then they're like that's

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that's the most they're like we how

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about 8.5 like ah okay great great job

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great job next day it's like can you do

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eight meters instead of 8.5 they're like

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okay and then and then some and that

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takes weeks and weeks and weeks

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and what you're saying is there are a

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couple downsides to this cognitive the

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traditional cognitive behavioral therapy

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one is that the long amount of time it

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takes and then two is that even when

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you're supposedly cured something

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traumatic can happen again that can

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trigger you back to being at Baseline

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Baseline fear level where you were

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before okay so uh this was very well

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explained and the so the idea is that we

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know from so we have an experimental

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um uh model to understand

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um exposure treatment or cognitive

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behavior treatment and and this is so we

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can learn for instance uh rats

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um by presenting a neutral stimulus a

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tone which is followed by painful

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stimulus or shock and then after a

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couple of learning trials they so they

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if we only present them the new

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originally neutral troll they react with

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a freezing response so that means that a

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what we call a fair memory has been

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formed which is a association between

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the originally neutral stimulus the tone

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and the shock and that when they are

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only presented to the tone they respond

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as if they are also presented they

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expect also to be presented to a shock

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even though they are not

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exposed to a shark anymore

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and then you can also extinguish the

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fear by repeatedly exposing them to the

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tone without a shock and then after many

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many tries you see a gradual decline of

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fear but then if you just wait a couple

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of weeks or you change the context then

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it's very easy to trigger the fear

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response again so you see very easily a

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return of fear and we know from the

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animal uh research that this can be

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explained that Extinction learning even

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though is a very effective procedure to

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reduce the Learned Fair response it does

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not erase the original fear memory so

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the fear Memory Remains intact and the

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new sort of Extinction memory is formed

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that competes for Behavioral control

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with the original fear memory but the

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original fear memory is extremely strong

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and very often winds from the extinction

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memory and that this explains actually

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the return of fear so until the

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um yeah around the world two thousand or

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so it was a sort of accepted few that we

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can never change the fear memory and the

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best thing that we can do is actually

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forming a new Extinction memory and all

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the new approaches that tries to improve

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the cognitive behavior treatment was

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actually

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aimed to strengthen or enhance the

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extinction memory so after my PhD at the

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University of Amsterdam I moved to

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Maastricht University and that also my

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clinical training so I saw many patients

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with fear and phobias and post-traumatic

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stress disorder I was well known with

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the literature also with the

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Neuroscience literature and I was sort

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of for a year thinking well how can we

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somehow mislead our brain and sort of

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weaken the fear memory itself would that

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be possible and then I discovered early

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I think in 2002 or three three indeed

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because that was the year that the paper

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of Grenada appeared

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the paper by Cream Nader showing that it

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might be possible to change the

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underlying or to weaken the underlying

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fear memory

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and so what they did in in rodents they

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first learned this um fear are

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presenting the rodents with a tone and a

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shock and then testing them a couple of

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days later you see an expression of the

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fear memory by freezing a response if

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they are only presented to the tone and

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what they did is instead of an

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Extinction procedure they reactivated

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the fair memory

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by presenting them to a single tone and

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then injected the animals with a protein

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synthesis inhibitor

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anisomycin a very toxic drug

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which you cannot use in humans but they

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did so in in the rodents

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and then if they tested the animals a

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couple of hours later there was still a

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very strong expression of the fair

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memory but then 24 hours later

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the fear was almost gone as if there was

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no longer an expression of the fear

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memory

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yeah this was really sort of this change

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terrible idea of memory because until

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then we thought that after memory is

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consolidated

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so maybe can dive a little bit into the

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basics of Neuroscience on on memory so

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if if organisms learn something and you

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test them for instance within an hour we

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speak of short-term memory so if they

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have learned a memorized but they well

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if there's memory of what they learn

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there's a short-term memory and in order

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to transfer the short-term memory into a

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long-term memory uh protein synthesis is

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necessary

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and if you block the protein synthesis

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there is it is not possible to form a

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long-term memory so then if you test the

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animals for instance 24 hours later you

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don't see any expression anymore

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but the sort of accepted few or dominant

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few in um memory literature was that

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after memory has been Consolidated we

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cannot change the original memory trade

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Trace so the only way to change our

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memory is by forming new memory traces

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that interfere with the original memory

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Trace so this seminal study by crem

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Nader showed that it may be possible

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even after memory consolidation to

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change the original memory trace and

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that if you reactivate memory that the

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receiving of the memory requires again

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protein synthesis and this means that if

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you

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interfere with these processes with the

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protein synthesis

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required for the rewriting of the

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previously formed memory

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then we may be able to change

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fear memory itself

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right and just to interrupt if I'm

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understanding correctly you make a mouse

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or rat or whatever it is extremely

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afraid of some stimulus let's call it a

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tone in this case then you can make it

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afraid Again by repeating the stimulus

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and afterwards you inject it with a

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neurotoxic I believe it's just toxic in

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general but I don't know neurotoxic

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chemical at least that prevents this

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protein from synthesizing or inhibits

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this protein in some way the one that

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would entrench this memory and then it

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would eliminate the fear response

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because that memory is no longer being

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fortified is that correct yeah almost so

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what happens is if you and I come come

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later to that because it really depends

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on very specific circumstances whether

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the memory Trace is stabilized so if you

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retrieve a memory it's not always the

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case that the memory Trace is becomes in

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a sort of label or destabilized face but

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if so then after destabilization it

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requires protein synthesis to be

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re-stabilized again

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and normally that is what happens so

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memory reconsolidation is a way of

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updating the memory so if the memory

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should

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environment does not change but if the

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environment changes the memory should be

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changed a bit because while the whole

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idea of memory is that it is a sort of

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well it makes us very adaptive because

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it helps us to to better respond to the

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environment so if the environment does

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not change the memory or should also not

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change if it changes then the memory can

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either be changed by forming new memory

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traces or by

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updating the original memory Trace so

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would you please elaborate a little bit

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on how you arrived at the idea that

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taking these better occurs after the

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exposure stimulus is what's efficacious

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as opposed to before so after reading

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this seminal study by crem Nader that

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appeared in 2000 so at the turn of the

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century I became really thrilled because

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I thought if we can translate this

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finding to the human field this might

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sort of implicate that we really can

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sort of treat people with irrational

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fears and anxiety disorders and maybe

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also responsible success disorder which

281
00:11:50,690 --> 00:11:48,180
are much more effective intervention and

282
00:11:53,630 --> 00:11:50,700
this could be a solution for the higher

283
00:11:55,970 --> 00:11:53,640
relapse rate but the anisomycin protein

284
00:11:59,449 --> 00:11:55,980
synthesis can clearly not be used in

285
00:12:01,310 --> 00:11:59,459
humans this is very toxic and also what

286
00:12:03,949 --> 00:12:01,320
we can do is

287
00:12:06,769 --> 00:12:03,959
uh inject the drug directly into the

288
00:12:08,569 --> 00:12:06,779
brain into the amygdala the the the the

289
00:12:10,030 --> 00:12:08,579
fear center of the brain and that is

290
00:12:15,290 --> 00:12:10,040
what for instance

291
00:12:18,350 --> 00:12:15,300
also many other uh animal researches but

292
00:12:20,870 --> 00:12:18,360
uh in 2004 and also

293
00:12:25,430 --> 00:12:20,880
um a little bit before that year there

294
00:12:28,490 --> 00:12:25,440
were a couple of studies testing uh the

295
00:12:30,889 --> 00:12:28,500
same ID but then with propanolol the

296
00:12:33,410 --> 00:12:30,899
noradrinootic beta blocker so we only

297
00:12:35,930 --> 00:12:33,420
give 40 milligrams and only once it's

298
00:12:39,710 --> 00:12:35,940
not very clearly not very toxic for

299
00:12:42,530 --> 00:12:39,720
humans in our first study we gave

300
00:12:45,230 --> 00:12:42,540
Propranolol actually before the memory

301
00:12:47,690 --> 00:12:45,240
reactivation and not to dampen the fear

302
00:12:50,329 --> 00:12:47,700
response but we reasoned that if you

303
00:12:52,370 --> 00:12:50,339
reactivate a fair memory then the

304
00:12:54,050 --> 00:12:52,380
processes of memory destabilization and

305
00:12:56,329 --> 00:12:54,060
re-stabilization probably start

306
00:12:58,970 --> 00:12:56,339
immediately following the memory

307
00:13:02,389 --> 00:12:58,980
retrieval and it takes between one and

308
00:13:04,310 --> 00:13:02,399
two hours before propranolol has passed

309
00:13:05,990 --> 00:13:04,320
the blood brain barrier and reaches a

310
00:13:09,889 --> 00:13:06,000
peak level so we thought if we give it

311
00:13:12,050 --> 00:13:09,899
afterwards we may miss the window

312
00:13:14,269 --> 00:13:12,060
but then of course if you give it before

313
00:13:16,069 --> 00:13:14,279
memory reactivation you never know

314
00:13:18,650 --> 00:13:16,079
whether it somehow interferes with the

315
00:13:20,690 --> 00:13:18,660
retrieval so that was why in later

316
00:13:22,970 --> 00:13:20,700
studies so it worked very well and then

317
00:13:25,670 --> 00:13:22,980
in later studies we always now give it

318
00:13:27,050 --> 00:13:25,680
after the memory reactivation but we

319
00:13:30,050 --> 00:13:27,060
don't use it

320
00:13:33,110 --> 00:13:30,060
to dampen the fear response but nor

321
00:13:35,750 --> 00:13:33,120
adrenaline as a neurotransmitter is

322
00:13:37,610 --> 00:13:35,760
indirectly involved in the protein

323
00:13:39,769 --> 00:13:37,620
synthesis necessary for memory

324
00:13:41,569 --> 00:13:39,779
consolidation and also for memory

325
00:13:44,030 --> 00:13:41,579
reconsolidation

326
00:13:46,550 --> 00:13:44,040
so this is the reason why we can also

327
00:13:47,930 --> 00:13:46,560
work with Propranolol instead of working

328
00:13:50,030 --> 00:13:47,940
with protein

329
00:13:52,190 --> 00:13:50,040
synthesis blockers

330
00:13:54,470 --> 00:13:52,200
would you say then that the difference

331
00:13:56,930 --> 00:13:54,480
between your approach and cognitive

332
00:13:58,790 --> 00:13:56,940
behavioral therapy is the focus on the

333
00:14:01,670 --> 00:13:58,800
recollection of memory and the

334
00:14:04,670 --> 00:14:01,680
destruction of the initial fear memory

335
00:14:07,190 --> 00:14:04,680
as opposed to trying to build barrier

336
00:14:10,250 --> 00:14:07,200
memories that would inhibit that

337
00:14:12,610 --> 00:14:10,260
original fear response yeah indeed the

338
00:14:15,590 --> 00:14:12,620
difference is that instead of

339
00:14:17,990 --> 00:14:15,600
building new memories or trying to

340
00:14:20,750 --> 00:14:18,000
control and be emotional memory and

341
00:14:24,410 --> 00:14:20,760
emotional responses we try to

342
00:14:26,629 --> 00:14:24,420
to yeah mitigate the uh the root of the

343
00:14:29,329 --> 00:14:26,639
disorder so to weaken the fear memory

344
00:14:32,690 --> 00:14:29,339
itself procedurally it's also very

345
00:14:34,430 --> 00:14:32,700
different because exposure treatment

346
00:14:37,009 --> 00:14:34,440
yeah the idea is that it actually

347
00:14:40,310 --> 00:14:37,019
targets more the cognitive processes so

348
00:14:42,430 --> 00:14:40,320
the expectancies it's a it's a longer

349
00:14:44,590 --> 00:14:42,440
process so by re

350
00:14:46,790 --> 00:14:44,600
beatingly people

351
00:14:50,750 --> 00:14:46,800
exposing to the feared queue they

352
00:14:55,069 --> 00:14:50,760
gradually learn that uh what they fear

353
00:14:58,069 --> 00:14:55,079
is is irrational whereas we expose our

354
00:15:00,710 --> 00:14:58,079
um participants only very briefly

355
00:15:04,310 --> 00:15:00,720
between two and five minutes to the

356
00:15:07,490 --> 00:15:04,320
third queue so we don't

357
00:15:09,590 --> 00:15:07,500
targets the cognitive system and what is

358
00:15:13,310 --> 00:15:09,600
interesting what we see is first we see

359
00:15:18,350 --> 00:15:13,320
a behavior change so we so we reduce the

360
00:15:21,530 --> 00:15:18,360
defensive reflex or in phobics we change

361
00:15:23,329 --> 00:15:21,540
the avoidance behavior and when I say

362
00:15:25,430 --> 00:15:23,339
first you see the change are you talking

363
00:15:26,509 --> 00:15:25,440
about after you give the beta blocker

364
00:15:27,650 --> 00:15:26,519
and then you wait 20 minutes they're

365
00:15:30,230 --> 00:15:27,660
talking about that and then for the next

366
00:15:33,590 --> 00:15:30,240
day we actually we found and we

367
00:15:36,590 --> 00:15:33,600
published that paper in 2018 and when

368
00:15:39,350 --> 00:15:36,600
you test them 12 hours later on the same

369
00:15:41,329 --> 00:15:39,360
day you still see them same fear

370
00:15:42,110 --> 00:15:41,339
expression but only after a night of

371
00:15:45,650 --> 00:15:42,120
sleep

372
00:15:48,530 --> 00:15:45,660
uh we see the sudden very abrupt

373
00:15:50,569 --> 00:15:48,540
reduction of fear so instead of the

374
00:15:55,850 --> 00:15:50,579
gradual decline of the fear response

375
00:15:58,069 --> 00:15:55,860
it's delayed So after 24 hours but very

376
00:16:00,650 --> 00:15:58,079
um abrupt and that

377
00:16:04,189 --> 00:16:00,660
especially when when

378
00:16:06,769 --> 00:16:04,199
I treat uh patients and and it is a

379
00:16:10,189 --> 00:16:06,779
successful treatment it's every time

380
00:16:13,129 --> 00:16:10,199
feels like magic because

381
00:16:14,750 --> 00:16:13,139
yeah normally you see a sort of you are

382
00:16:18,110 --> 00:16:14,760
there when you see sort of gradual

383
00:16:20,930 --> 00:16:18,120
change in behavior and now first you see

384
00:16:23,689 --> 00:16:20,940
during the exposure that people are

385
00:16:27,290 --> 00:16:23,699
really as an intense fear response are

386
00:16:30,230 --> 00:16:27,300
sometimes crying and and panicking and

387
00:16:32,629 --> 00:16:30,240
then if they come back 24 hours later

388
00:16:34,810 --> 00:16:32,639
they are able to it's not that they

389
00:16:38,329 --> 00:16:34,820
entirely relaxed

390
00:16:40,310 --> 00:16:38,339
uh but yeah there's such a huge

391
00:16:43,810 --> 00:16:40,320
difference so that

392
00:16:46,610 --> 00:16:43,820
really feels like uh it cannot be true

393
00:16:48,650 --> 00:16:46,620
I'm curious you had mentioned the

394
00:16:51,889 --> 00:16:48,660
relationship between protein synthesis

395
00:16:54,350 --> 00:16:51,899
and fear it is known that for protein

396
00:16:57,530 --> 00:16:54,360
synthesis that this is deeply tied with

397
00:17:00,050 --> 00:16:57,540
our genetics the sort of manuscript for

398
00:17:02,990 --> 00:17:00,060
the creation of all of our proteins do

399
00:17:06,650 --> 00:17:03,000
you think it is for this reason that

400
00:17:09,110 --> 00:17:06,660
one finds that in epigenetics that there

401
00:17:11,150 --> 00:17:09,120
are inherited fears does that have a

402
00:17:14,210 --> 00:17:11,160
connection to your research

403
00:17:16,610 --> 00:17:14,220
yeah no I I'm what do you mean with

404
00:17:18,710 --> 00:17:16,620
inherited fears because I'm a bit I mean

405
00:17:20,929 --> 00:17:18,720
that was also one of the questions that

406
00:17:23,150 --> 00:17:20,939
the fear of snakes I mean the fears that

407
00:17:26,689 --> 00:17:23,160
we treat is of is are the irrational

408
00:17:29,150 --> 00:17:26,699
fears so not I mean

409
00:17:31,130 --> 00:17:29,160
of course I mean snakes can be dangerous

410
00:17:33,530 --> 00:17:31,140
but there's no reason to be really

411
00:17:36,830 --> 00:17:33,540
phobic in a sense that you

412
00:17:38,930 --> 00:17:36,840
that people avoid several places because

413
00:17:41,510 --> 00:17:38,940
there could be a snake whereas there is

414
00:17:43,970 --> 00:17:41,520
no snake or so that is the kind of fear

415
00:17:47,930 --> 00:17:43,980
that we treat

416
00:17:50,930 --> 00:17:47,940
um there was an article uh published on

417
00:17:52,730 --> 00:17:50,940
it was an epigenetic study where they I

418
00:17:56,049 --> 00:17:52,740
believe they

419
00:17:59,270 --> 00:17:56,059
induced a fear of response

420
00:18:03,710 --> 00:17:59,280
to rodents at the sound of a bell

421
00:18:05,810 --> 00:18:03,720
and they made a very visceral pain for

422
00:18:10,010 --> 00:18:05,820
the rodents at the sound of that Bell

423
00:18:12,590 --> 00:18:10,020
they then allowed the rodents to uh have

424
00:18:14,770 --> 00:18:12,600
their next generation of Offspring and

425
00:18:17,289 --> 00:18:14,780
then gave them the sound of that Bell

426
00:18:20,390 --> 00:18:17,299
apparently the rodents were afraid

427
00:18:22,850 --> 00:18:20,400
although never hearing the Bell before

428
00:18:25,130 --> 00:18:22,860
or feeling tortured at this hearing of

429
00:18:25,850 --> 00:18:25,140
the Bell were afraid at the sound of the

430
00:18:29,750 --> 00:18:25,860
Bell

431
00:18:32,810 --> 00:18:29,760
for what is even more amazing is that

432
00:18:36,470 --> 00:18:32,820
the generation after the grandchildren

433
00:18:40,010 --> 00:18:36,480
they then gave the sound of the bell and

434
00:18:43,669 --> 00:18:40,020
had these rodents afraid so I'm curious

435
00:18:46,730 --> 00:18:43,679
if this link of fear this is inheritance

436
00:18:50,810 --> 00:18:46,740
of fear has something to do with uh

437
00:18:53,270 --> 00:18:50,820
epigenetic mechanisms on DNA considering

438
00:18:55,130 --> 00:18:53,280
that you were speaking of protein the

439
00:18:59,950 --> 00:18:55,140
relation between protein and synthesis

440
00:19:05,210 --> 00:19:02,870
I'm very curious to to read do you

441
00:19:08,450 --> 00:19:05,220
remember the authors of the paper

442
00:19:10,909 --> 00:19:08,460
I can find it and send it yeah please I

443
00:19:14,029 --> 00:19:10,919
don't know but somehow as if there is um

444
00:19:19,010 --> 00:19:14,039
indeed a memory of the fear that is

445
00:19:24,470 --> 00:19:22,610
by the way does this only work on fear

446
00:19:25,970 --> 00:19:24,480
memories like post-traumatic stress

447
00:19:27,289 --> 00:19:25,980
disorder or can it work on people who

448
00:19:28,549 --> 00:19:27,299
have innate fears like we were

449
00:19:30,049 --> 00:19:28,559
mentioning before some people are afraid

450
00:19:33,890 --> 00:19:30,059
of snakes innately some people are

451
00:19:35,630 --> 00:19:33,900
afraid of blood that's more discussed no

452
00:19:37,610 --> 00:19:35,640
yeah well we tested that because in a

453
00:19:40,669 --> 00:19:37,620
few conditioning procedure so what we do

454
00:19:41,330 --> 00:19:40,679
is uh we work with pictures and

455
00:19:45,350 --> 00:19:41,340
um

456
00:19:48,590 --> 00:19:45,360
an electric uh stimulus administered to

457
00:19:50,990 --> 00:19:48,600
the wrist so painful stimulus so we also

458
00:19:54,770 --> 00:19:51,000
use the fair conditioning model in the

459
00:19:58,250 --> 00:19:54,780
laboratory and and an innate fear is not

460
00:20:00,110 --> 00:19:58,260
the fear but we go to the to the Learned

461
00:20:02,510 --> 00:20:00,120
stimulus or the picture followed by the

462
00:20:03,890 --> 00:20:02,520
shock but actually the response to the

463
00:20:06,110 --> 00:20:03,900
shock itself

464
00:20:10,250 --> 00:20:06,120
and that didn't change so it's not that

465
00:20:13,130 --> 00:20:10,260
we in that sense dampen the that is what

466
00:20:16,310 --> 00:20:13,140
what you could expect if you dampen your

467
00:20:18,470 --> 00:20:16,320
whole fear system that people or or

468
00:20:21,650 --> 00:20:18,480
animals don't respond anymore to

469
00:20:26,210 --> 00:20:21,660
intrinsically uh threatening stimuli

470
00:20:27,890 --> 00:20:26,220
like pain or or a threatening animal and

471
00:20:32,029 --> 00:20:27,900
that's that this is not what happens

472
00:20:33,950 --> 00:20:32,039
it's really to the Learned fears

473
00:20:35,690 --> 00:20:33,960
and you mentioned that what's required

474
00:20:37,610 --> 00:20:35,700
is a night's rest

475
00:20:40,370 --> 00:20:37,620
in order for your for your treatment to

476
00:20:41,690 --> 00:20:40,380
be effective have you measured the

477
00:20:44,390 --> 00:20:41,700
quality of someone's sleep to the

478
00:20:46,310 --> 00:20:44,400
extinction of the fear this is what we

479
00:20:48,770 --> 00:20:46,320
are currently testing but unfortunately

480
00:20:51,289 --> 00:20:48,780
the the study we had to stop with the

481
00:20:54,169 --> 00:20:51,299
data collection due to covid-19 so

482
00:20:57,110 --> 00:20:54,179
hopefully we can proceed with our study

483
00:21:00,350 --> 00:20:57,120
after the summer but so this is so what

484
00:21:03,529 --> 00:21:00,360
we did is we controlled for the 40 hours

485
00:21:05,750 --> 00:21:03,539
so because from the animal literature we

486
00:21:07,730 --> 00:21:05,760
learned that is that reconsolidation is

487
00:21:09,470 --> 00:21:07,740
time dependent

488
00:21:11,450 --> 00:21:09,480
um so we started first with a pilot

489
00:21:14,330 --> 00:21:11,460
study and then we discovered that yeah

490
00:21:16,789 --> 00:21:14,340
when you wait five or six hours it was

491
00:21:18,529 --> 00:21:16,799
still such a strong fear expression and

492
00:21:20,990 --> 00:21:18,539
we always you know our previous studies

493
00:21:25,850 --> 00:21:21,000
we always tested the next day

494
00:21:29,930 --> 00:21:25,860
for the effect and and it takes also

495
00:21:32,690 --> 00:21:29,940
um well propanol has um five hour half

496
00:21:34,730 --> 00:21:32,700
time failure so after 12 hours it's

497
00:21:36,649 --> 00:21:34,740
almost completely out of the body and

498
00:21:39,169 --> 00:21:36,659
especially the next day it's completely

499
00:21:41,270 --> 00:21:39,179
gone so then you are also sure that what

500
00:21:42,950 --> 00:21:41,280
you measure can no longer be a

501
00:21:44,270 --> 00:21:42,960
propanolol effect

502
00:21:45,770 --> 00:21:44,280
and

503
00:21:48,110 --> 00:21:45,780
um

504
00:21:51,169 --> 00:21:48,120
so we piloted first and tested five

505
00:21:53,870 --> 00:21:51,179
hours and then a certain moment I asked

506
00:21:55,970 --> 00:21:53,880
my poster maybe you could test also 12

507
00:21:57,770 --> 00:21:55,980
hours later on the same day and we still

508
00:22:00,110 --> 00:21:57,780
found such a strong fear response and

509
00:22:02,330 --> 00:22:00,120
then we decided to study where we either

510
00:22:04,730 --> 00:22:02,340
did a treatment in the morning tested

511
00:22:06,890 --> 00:22:04,740
them 12 hours later on the same day and

512
00:22:10,250 --> 00:22:06,900
then again the next day or we treated

513
00:22:12,049 --> 00:22:10,260
them in the evening just also waited 12

514
00:22:13,610 --> 00:22:12,059
hours but it was a night of sleep in

515
00:22:16,070 --> 00:22:13,620
between and then the next day and we

516
00:22:19,130 --> 00:22:16,080
really saw that it was not a time but a

517
00:22:21,230 --> 00:22:19,140
night of sleep but we did not register

518
00:22:23,510 --> 00:22:21,240
the Sleep Quality we don't know which

519
00:22:27,289 --> 00:22:23,520
phase of the sleep is important so these

520
00:22:30,350 --> 00:22:27,299
are yeah very interesting next steps we

521
00:22:34,029 --> 00:22:30,360
also tested uh the time we know during

522
00:22:35,570 --> 00:22:34,039
which we can actually give propanolol so

523
00:22:39,830 --> 00:22:35,580
uh

524
00:22:42,529 --> 00:22:39,840
after memory activation and it still

525
00:22:44,810 --> 00:22:42,539
works but two hours after memory

526
00:22:46,510 --> 00:22:44,820
retrieved then it's really too late so

527
00:22:49,430 --> 00:22:46,520
that also shows that there's a really

528
00:22:51,909 --> 00:22:49,440
specific time window that you can Target

529
00:22:55,130 --> 00:22:51,919
these processes and otherwise you are

530
00:22:57,850 --> 00:22:55,140
too late can fear Extinction work on

531
00:23:01,010 --> 00:22:57,860
relatively minor issues so for example

532
00:23:02,990 --> 00:23:01,020
if someone were to approach if someone

533
00:23:06,830 --> 00:23:03,000
were nervous speaking in front of others

534
00:23:10,010 --> 00:23:06,840
could they use this treatment to get rid

535
00:23:12,649 --> 00:23:10,020
of those minor fears social fears are in

536
00:23:16,070 --> 00:23:12,659
that sense not so easy because people we

537
00:23:19,070 --> 00:23:16,080
we did a study uh in people who have a

538
00:23:21,289 --> 00:23:19,080
fear of public speaking and that the

539
00:23:23,270 --> 00:23:21,299
treatment was not effective and the

540
00:23:26,330 --> 00:23:23,280
problem in research is done that you for

541
00:23:28,190 --> 00:23:26,340
instance work with a standard protocol

542
00:23:31,070 --> 00:23:28,200
that is already quite difficult for

543
00:23:33,549 --> 00:23:31,080
people who suffer from social fears

544
00:23:36,289 --> 00:23:33,559
because these fears are generally very

545
00:23:38,510 --> 00:23:36,299
idiosyncratic but especially with social

546
00:23:40,850 --> 00:23:38,520
Affairs people very often they their

547
00:23:43,669 --> 00:23:40,860
fears actually but other people think

548
00:23:46,730 --> 00:23:43,679
for instance and it is really hard to to

549
00:23:49,669 --> 00:23:46,740
expose people to that and our issue is

550
00:23:52,610 --> 00:23:49,679
that the threat

551
00:23:55,669 --> 00:23:52,620
or the anticipated catastrophe does not

552
00:23:58,669 --> 00:23:55,679
necessarily happen in a specific time

553
00:24:01,370 --> 00:23:58,679
window so if what people fear can happen

554
00:24:04,730 --> 00:24:01,380
for instance a year later then a

555
00:24:06,830 --> 00:24:04,740
treatment cannot be applied because it

556
00:24:08,570 --> 00:24:06,840
really should be in the moment that you

557
00:24:10,909 --> 00:24:08,580
trigger the memory and then something

558
00:24:12,049 --> 00:24:10,919
they can learn something from from their

559
00:24:14,750 --> 00:24:12,059
environment

560
00:24:16,909 --> 00:24:14,760
with respect to their fear and there are

561
00:24:19,970 --> 00:24:16,919
also many fears I mean when people are

562
00:24:22,430 --> 00:24:19,980
afraid of of dying very often that that

563
00:24:24,890 --> 00:24:22,440
this is not something that that the

564
00:24:27,350 --> 00:24:24,900
thing will happen in the near future but

565
00:24:29,270 --> 00:24:27,360
maybe in a year or so

566
00:24:31,909 --> 00:24:29,280
so for that kind of fear the treatment

567
00:24:34,549 --> 00:24:31,919
is not suitable

568
00:24:37,909 --> 00:24:34,559
are there other it seems to me that this

569
00:24:40,070 --> 00:24:37,919
is almost like a surgical knife yeah

570
00:24:42,770 --> 00:24:40,080
cognitively speaking that you are

571
00:24:45,230 --> 00:24:42,780
removing sectors of fear and of memory

572
00:24:48,049 --> 00:24:45,240
and the more clean-cut and defined those

573
00:24:51,169 --> 00:24:48,059
fears are the better they can be removed

574
00:24:53,750 --> 00:24:51,179
are there other complicating factors in

575
00:24:55,070 --> 00:24:53,760
this mental surgery

576
00:25:01,190 --> 00:24:55,080
yeah

577
00:25:03,830 --> 00:25:01,200
in a paper kind of sort of as a matter

578
00:25:05,890 --> 00:25:03,840
for a neurosurgery or so and it's in

579
00:25:09,590 --> 00:25:05,900
that sounds very different from uh

580
00:25:11,990 --> 00:25:09,600
Psychotherapy uh yeah it is even one of

581
00:25:13,310 --> 00:25:12,000
your I think last questions

582
00:25:16,610 --> 00:25:13,320
um

583
00:25:19,190 --> 00:25:16,620
because after so we first showed this uh

584
00:25:21,649 --> 00:25:19,200
this this effect in the laboratory in in

585
00:25:25,310 --> 00:25:21,659
dozens of studies which is a sort of

586
00:25:27,890 --> 00:25:25,320
proof of principle then we tested it in

587
00:25:30,470 --> 00:25:27,900
uh people with fear of spiders

588
00:25:32,750 --> 00:25:30,480
and and then of course I received many

589
00:25:34,909 --> 00:25:32,760
questions for people who are suffering

590
00:25:37,010 --> 00:25:34,919
from uh crippling fear so if it's so

591
00:25:39,470 --> 00:25:37,020
easy I can also do it myself expose

592
00:25:41,870 --> 00:25:39,480
myself to the queue take the pill and

593
00:25:44,750 --> 00:25:41,880
then the fear is gone but yeah

594
00:25:47,269 --> 00:25:44,760
unfortunately it's it's not easy because

595
00:25:49,190 --> 00:25:47,279
there are many boundary conditions and

596
00:25:52,909 --> 00:25:49,200
it has to do with

597
00:25:55,310 --> 00:25:52,919
the idea that if you are exposed to the

598
00:25:59,210 --> 00:25:55,320
feared queue it's not necessarily so

599
00:26:01,430 --> 00:25:59,220
that the memory is uh

600
00:26:04,250 --> 00:26:01,440
uh destabilized

601
00:26:07,370 --> 00:26:04,260
and if the exposure for instance is to

602
00:26:09,470 --> 00:26:07,380
so either it is not there's nothing new

603
00:26:12,590 --> 00:26:09,480
to be learned then it's a sort of

604
00:26:16,570 --> 00:26:12,600
passive retrieval it could also be that

605
00:26:20,149 --> 00:26:16,580
a situation is too new or too different

606
00:26:23,870 --> 00:26:20,159
from from their original fear and then

607
00:26:25,490 --> 00:26:23,880
this is a sort of can yeah

608
00:26:28,730 --> 00:26:25,500
um

609
00:26:31,029 --> 00:26:28,740
sort of initiation of the formation of a

610
00:26:34,070 --> 00:26:31,039
new memory or of an Extinction memory

611
00:26:35,990 --> 00:26:34,080
and whether you target the process of

612
00:26:38,269 --> 00:26:36,000
memory reconciliation is really in

613
00:26:40,610 --> 00:26:38,279
between a sort of passive retrieval

614
00:26:43,490 --> 00:26:40,620
process and the formation of a new

615
00:26:46,850 --> 00:26:43,500
memory and the problem is that we do not

616
00:26:48,529 --> 00:26:46,860
have a sort of index that we can use to

617
00:26:51,409 --> 00:26:48,539
know what is happening in the brain

618
00:26:53,690 --> 00:26:51,419
during the memory reactivation

619
00:26:57,049 --> 00:26:53,700
so we only have the behavior

620
00:26:58,330 --> 00:26:57,059
the readout of memory but the fair

621
00:27:00,190 --> 00:26:58,340
reaction is not

622
00:27:02,090 --> 00:27:00,200
[Music]

623
00:27:04,490 --> 00:27:02,100
informative

624
00:27:06,470 --> 00:27:04,500
on what happens actually in the brain on

625
00:27:08,510 --> 00:27:06,480
whether it's only a passive retrieval

626
00:27:13,070 --> 00:27:08,520
process or whether the memory

627
00:27:15,350 --> 00:27:13,080
reconsolidation is triggers so this is

628
00:27:18,110 --> 00:27:15,360
a huge Challenge and our current

629
00:27:19,730 --> 00:27:18,120
research is trying to tackle this this

630
00:27:23,330 --> 00:27:19,740
problem especially

631
00:27:25,310 --> 00:27:23,340
in translating to clinical practice so

632
00:27:26,510 --> 00:27:25,320
what we do now and so I'm now sitting

633
00:27:31,310 --> 00:27:26,520
here in

634
00:27:34,130 --> 00:27:31,320
in my clinic we opened a clinic uh a

635
00:27:34,990 --> 00:27:34,140
year ago where we treat many people with

636
00:27:38,029 --> 00:27:35,000
um

637
00:27:40,070 --> 00:27:38,039
suffering from fears and phobias so what

638
00:27:43,310 --> 00:27:40,080
we do now is

639
00:27:45,830 --> 00:27:43,320
partly intuitively so to decide when do

640
00:27:47,870 --> 00:27:45,840
we stop so you expose people ahead to

641
00:27:52,630 --> 00:27:47,880
the to the field queue it could be a dog

642
00:27:56,990 --> 00:27:52,640
a kitten a spider uh Heights whatever

643
00:27:59,930 --> 00:27:57,000
okay how how long should you exposure be

644
00:28:02,269 --> 00:27:59,940
such that we trigger the so we

645
00:28:04,549 --> 00:28:02,279
destabilize the memory but that is not

646
00:28:06,710 --> 00:28:04,559
too long certainly that it becomes

647
00:28:08,029 --> 00:28:06,720
already an exposure treatment and that

648
00:28:10,190 --> 00:28:08,039
is yeah

649
00:28:12,409 --> 00:28:10,200
really a challenge

650
00:28:14,269 --> 00:28:12,419
something I was thinking about it there

651
00:28:16,789 --> 00:28:14,279
are people with childhood traumas and

652
00:28:19,010 --> 00:28:16,799
various other anxieties and I was

653
00:28:21,529 --> 00:28:19,020
wondering well instead of exposing them

654
00:28:23,630 --> 00:28:21,539
to whatever stimulus would cause them to

655
00:28:25,789 --> 00:28:23,640
feel the extreme fear given that

656
00:28:28,450 --> 00:28:25,799
sometimes that's impractical especially

657
00:28:30,950 --> 00:28:28,460
now during covet can they with

658
00:28:35,710 --> 00:28:30,960
tremendous effort concerted mental

659
00:28:38,990 --> 00:28:35,720
effort just think about that stimulus to

660
00:28:40,250 --> 00:28:39,000
hallucinate in a sense Their Fear and

661
00:28:41,810 --> 00:28:40,260
and instead of bringing their fear

662
00:28:42,830 --> 00:28:41,820
response up to 10 out of 10 which is

663
00:28:44,870 --> 00:28:42,840
what you try to do in your practice

664
00:28:46,970 --> 00:28:44,880
bring it up to four out of ten because

665
00:28:49,070 --> 00:28:46,980
obviously it's not the same as having

666
00:28:51,350 --> 00:28:49,080
let's say a mask murderer

667
00:28:53,450 --> 00:28:51,360
in front of you and you imagining a mask

668
00:28:54,649 --> 00:28:53,460
murderer or a person in a mess let's say

669
00:28:56,870 --> 00:28:54,659
they're they're afraid of the scream

670
00:28:58,730 --> 00:28:56,880
mask from that 90s movie so they imagine

671
00:29:00,769 --> 00:28:58,740
the scream mask okay they imagined it

672
00:29:03,409 --> 00:29:00,779
and they're triggering themselves up to

673
00:29:04,789 --> 00:29:03,419
four out of ten then they take the beta

674
00:29:06,649 --> 00:29:04,799
blocker now

675
00:29:08,390 --> 00:29:06,659
imagine they do that

676
00:29:10,730 --> 00:29:08,400
well first of all would that work at all

677
00:29:12,110 --> 00:29:10,740
and second of all if if let's say it

678
00:29:14,390 --> 00:29:12,120
doesn't work do you imagine it would

679
00:29:16,870 --> 00:29:14,400
work if they did that a few times your

680
00:29:18,769 --> 00:29:16,880
treatment is like one Extinction event

681
00:29:20,690 --> 00:29:18,779
eradicate that memory from one treatment

682
00:29:22,310 --> 00:29:20,700
but do you imagine this four out of ten

683
00:29:24,130 --> 00:29:22,320
progressively over the course of two

684
00:29:26,870 --> 00:29:24,140
weeks let's say could bring it down to

685
00:29:29,690 --> 00:29:26,880
almost remove that memory at least the

686
00:29:31,549 --> 00:29:29,700
fear associated with it yeah uh now

687
00:29:33,889 --> 00:29:31,559
first of all we of course it is not

688
00:29:35,090 --> 00:29:33,899
necessarily so that even if it works

689
00:29:37,789 --> 00:29:35,100
that it is

690
00:29:39,470 --> 00:29:37,799
I mean memory emotional memory that

691
00:29:40,669 --> 00:29:39,480
underlies anxiety disorders and

692
00:29:43,250 --> 00:29:40,679
especially post-traumatic stress

693
00:29:46,430 --> 00:29:43,260
disorder is not a sort of single memory

694
00:29:48,889 --> 00:29:46,440
Trace but it is a network so you could

695
00:29:50,269 --> 00:29:48,899
imagine that for PTSD that you even if

696
00:29:52,490 --> 00:29:50,279
it works that you weak in the network

697
00:29:55,490 --> 00:29:52,500
but that you need more treatment

698
00:29:58,750 --> 00:29:55,500
sessions to really dismantle the

699
00:30:03,070 --> 00:29:58,760
underlying uh emotional memory

700
00:30:05,389 --> 00:30:03,080
we have have uh applied the

701
00:30:07,130 --> 00:30:05,399
reconciliation intervention already to

702
00:30:08,930 --> 00:30:07,140
to people suffering from post-traumatic

703
00:30:13,130 --> 00:30:08,940
stress disorder and this is in general

704
00:30:14,630 --> 00:30:13,140
the way also yeah if if you do if you

705
00:30:17,149 --> 00:30:14,640
use the standard cognitive behavior

706
00:30:19,850 --> 00:30:17,159
treatment you always work with uh

707
00:30:21,470 --> 00:30:19,860
imaginary exposure and the idea is that

708
00:30:24,230 --> 00:30:21,480
the trauma memory is actually the

709
00:30:26,950 --> 00:30:24,240
trigger like in dog phobia the dog draw

710
00:30:29,330 --> 00:30:26,960
my memory triggers an overwhelming

711
00:30:32,510 --> 00:30:29,340
emotional responses and people are

712
00:30:34,490 --> 00:30:32,520
afraid of being overwhelmed by their

713
00:30:36,470 --> 00:30:34,500
emotion responses and they feel like

714
00:30:39,110 --> 00:30:36,480
they cannot handle it they will become

715
00:30:42,470 --> 00:30:39,120
crazy losing control whatever

716
00:30:43,870 --> 00:30:42,480
so the reason to go back to the trauma

717
00:30:46,010 --> 00:30:43,880
is actually

718
00:30:47,990 --> 00:30:46,020
usually when people have intrusive

719
00:30:49,789 --> 00:30:48,000
memories they try to avoid it because

720
00:30:51,409 --> 00:30:49,799
they don't want to expose themselves to

721
00:30:53,510 --> 00:30:51,419
the trauma memory because it triggers

722
00:30:56,210 --> 00:30:53,520
very intense

723
00:30:58,370 --> 00:30:56,220
um difficult emotions and what you do in

724
00:31:00,470 --> 00:30:58,380
treatment then is you try to do that of

725
00:31:03,649 --> 00:31:00,480
course supporting the patient

726
00:31:06,830 --> 00:31:03,659
and and uh if you do

727
00:31:09,409 --> 00:31:06,840
rights then it triggers indeed the in

728
00:31:11,149 --> 00:31:09,419
yeah very strong emotional reactions and

729
00:31:13,190 --> 00:31:11,159
then they can experience that they do

730
00:31:15,529 --> 00:31:13,200
not die or that they are not

731
00:31:17,930 --> 00:31:15,539
going crazy over there first so this is

732
00:31:20,630 --> 00:31:17,940
then the sort of prediction error or new

733
00:31:22,450 --> 00:31:20,640
experience that may

734
00:31:27,529 --> 00:31:22,460
um

735
00:31:29,750 --> 00:31:27,539
then the Propranolol could work there is

736
00:31:32,510 --> 00:31:29,760
a in one of the I don't know whether you

737
00:31:34,850 --> 00:31:32,520
have seen the uh documentary by Lana

738
00:31:37,690 --> 00:31:34,860
Wilson a cure for fear so one of the

739
00:31:40,490 --> 00:31:37,700
four parts is the night in Kabul

740
00:31:42,529 --> 00:31:40,500
uh and this was a

741
00:31:45,769 --> 00:31:42,539
trauma treatment

742
00:31:47,750 --> 00:31:45,779
and there we used to

743
00:31:50,389 --> 00:31:47,760
um strengthen the memory reactivation

744
00:31:53,690 --> 00:31:50,399
also a um

745
00:31:56,810 --> 00:31:53,700
a virtual reality environment to make it

746
00:31:59,630 --> 00:31:56,820
a bit stronger too so to present him

747
00:32:03,370 --> 00:31:59,640
with some cues that could sort of yeah

748
00:32:05,870 --> 00:32:03,380
enhance the reactivation of the specific

749
00:32:07,789 --> 00:32:05,880
trauma memory but this is not always

750
00:32:09,590 --> 00:32:07,799
necessary sometimes people are very good

751
00:32:10,370 --> 00:32:09,600
in in

752
00:32:19,430 --> 00:32:10,380
um

753
00:32:21,110 --> 00:32:19,440
think psychedelics could have any any

754
00:32:23,210 --> 00:32:21,120
role in all this do you think it can

755
00:32:25,970 --> 00:32:23,220
perhaps enhance the effect let's say if

756
00:32:27,490 --> 00:32:25,980
the memory is not is is that is that the

757
00:32:29,810 --> 00:32:27,500
level of let's say four out of ten

758
00:32:31,490 --> 00:32:29,820
perhaps with a psychedelic experience

759
00:32:33,830 --> 00:32:31,500
this can

760
00:32:35,990 --> 00:32:33,840
get enhanced and and that way maybe we

761
00:32:38,090 --> 00:32:36,000
can do something about it reactivating

762
00:32:38,930 --> 00:32:38,100
that memory or is it too too much of a

763
00:32:41,389 --> 00:32:38,940
novel

764
00:32:43,370 --> 00:32:41,399
experience for someone who maybe hasn't

765
00:32:45,470 --> 00:32:43,380
done psychedelics before what are your

766
00:32:48,710 --> 00:32:45,480
speculations yeah well there are some

767
00:32:50,389 --> 00:32:48,720
some promising studies using MDMA for

768
00:32:52,789 --> 00:32:50,399
instance so I think the idea what is

769
00:32:55,430 --> 00:32:52,799
important of course is that that

770
00:32:57,409 --> 00:32:55,440
the research has a sort of at least

771
00:33:00,590 --> 00:32:57,419
plausible hypothesis on the working

772
00:33:03,169 --> 00:33:00,600
mechanism that's in my view important

773
00:33:05,269 --> 00:33:03,179
and whereas you very often see in in

774
00:33:08,330 --> 00:33:05,279
this field is that sort of drugs are

775
00:33:10,490 --> 00:33:08,340
just tested and so see

776
00:33:12,789 --> 00:33:10,500
just sure what it has an effect or not

777
00:33:16,610 --> 00:33:12,799
about it's not the way I like to work

778
00:33:18,769 --> 00:33:16,620
but there are I mean psychedelics could

779
00:33:19,490 --> 00:33:18,779
work by

780
00:33:21,529 --> 00:33:19,500
um

781
00:33:22,730 --> 00:33:21,539
they could help to destabilize the

782
00:33:24,950 --> 00:33:22,740
memory

783
00:33:28,190 --> 00:33:24,960
and yeah

784
00:33:31,009 --> 00:33:28,200
so and and then it is easier to yeah to

785
00:33:32,389 --> 00:33:31,019
to either and then maybe not I I don't

786
00:33:34,130 --> 00:33:32,399
think that you should then work maybe

787
00:33:35,690 --> 00:33:34,140
with Propranolol because then it could

788
00:33:37,730 --> 00:33:35,700
be also an interaction between the two

789
00:33:40,669 --> 00:33:37,740
at least you should make sure that it is

790
00:33:43,610 --> 00:33:40,679
not problematic uh but there are also

791
00:33:45,529 --> 00:33:43,620
behavior of course imagery scripting is

792
00:33:47,630 --> 00:33:45,539
a good way to to change the trauma

793
00:33:52,789 --> 00:33:47,640
memory and you could do that in

794
00:33:57,649 --> 00:33:56,090
right it will be really interesting to

795
00:33:59,450 --> 00:33:57,659
to do something in conjunction so

796
00:34:01,430 --> 00:33:59,460
perhaps we can maybe talk a little bit

797
00:34:02,750 --> 00:34:01,440
about that down the road that would be

798
00:34:05,450 --> 00:34:02,760
great yeah but but then the difference

799
00:34:07,549 --> 00:34:05,460
is because sometimes I mean cognitive

800
00:34:09,649 --> 00:34:07,559
behavior treatment is just

801
00:34:10,669 --> 00:34:09,659
combined with

802
00:34:13,070 --> 00:34:10,679
um

803
00:34:15,710 --> 00:34:13,080
with drugs but then it's only I mean

804
00:34:18,349 --> 00:34:15,720
drugs that also dampen the emotional

805
00:34:21,589 --> 00:34:18,359
response whereas the

806
00:34:24,829 --> 00:34:21,599
intriguing aspect here is that we use a

807
00:34:26,810 --> 00:34:24,839
drug uh not to dampen the emotion

808
00:34:29,149 --> 00:34:26,820
response but to really interfere with

809
00:34:32,030 --> 00:34:29,159
the yeah learning and memory processes

810
00:34:34,149 --> 00:34:32,040
which is a very different way of using a

811
00:34:37,970 --> 00:34:34,159
drug

812
00:34:41,990 --> 00:34:37,980
how far do these unlearning processes go

813
00:34:44,329 --> 00:34:42,000
is it possible to remove disgust or

814
00:34:47,389 --> 00:34:44,339
happiness for example or let's say a

815
00:34:50,930 --> 00:34:47,399
fond memory of something the opposite of

816
00:34:54,230 --> 00:34:50,940
fear are these future paths for This

817
00:34:56,750 --> 00:34:54,240
research or is it limited only within

818
00:35:00,290 --> 00:34:56,760
the scope of the phobic

819
00:35:02,870 --> 00:35:00,300
yeah certainly not limited to fears and

820
00:35:06,650 --> 00:35:02,880
phobias because it has

821
00:35:07,550 --> 00:35:06,660
also we tested for uh in the area of

822
00:35:09,829 --> 00:35:07,560
addiction

823
00:35:13,490 --> 00:35:09,839
first learn animals to become addicted

824
00:35:15,470 --> 00:35:13,500
to cocaine or other other drugs so

825
00:35:16,849 --> 00:35:15,480
addiction is also an associative memory

826
00:35:19,849 --> 00:35:16,859
like fears

827
00:35:22,370 --> 00:35:19,859
so there's a queue and an

828
00:35:24,170 --> 00:35:22,380
um yeah approach Behavior because the

829
00:35:29,390 --> 00:35:24,180
animal is addicted

830
00:35:31,730 --> 00:35:29,400
to it and um so in fears we

831
00:35:34,310 --> 00:35:31,740
aim to change the authorities behavior

832
00:35:36,650 --> 00:35:34,320
and in addiction you yeah then you

833
00:35:39,170 --> 00:35:36,660
should try to to change the approach

834
00:35:41,750 --> 00:35:39,180
Behavior so the other way

835
00:35:44,329 --> 00:35:41,760
and that is possible it is I think but

836
00:35:48,950 --> 00:35:44,339
it has not been I mean

837
00:35:52,930 --> 00:35:48,960
we are now in a pilot phase uh testing

838
00:35:55,910 --> 00:35:52,940
um people who are addicted to cigarettes

839
00:35:57,230 --> 00:35:55,920
uh but yeah

840
00:35:58,970 --> 00:35:57,240
so let's say someone's addicted to

841
00:36:00,290 --> 00:35:58,980
cigarettes or cocaine if they see the

842
00:36:01,609 --> 00:36:00,300
stimulus the cigarettes or the cocaine

843
00:36:03,109 --> 00:36:01,619
it triggers them they wanted smoke or

844
00:36:05,089 --> 00:36:03,119
they want to have cocaine again anyway

845
00:36:07,550 --> 00:36:05,099
if we're making an analog to the fear

846
00:36:09,770 --> 00:36:07,560
response the fear response situation is

847
00:36:12,410 --> 00:36:09,780
you provoke them intensely and then give

848
00:36:13,970 --> 00:36:12,420
them the beta blocker now in the

849
00:36:15,589 --> 00:36:13,980
addiction response do get them to smoke

850
00:36:16,970 --> 00:36:15,599
the cigarettes intensely or the cocaine

851
00:36:19,130 --> 00:36:16,980
intensely and then well obviously that's

852
00:36:20,510 --> 00:36:19,140
illegal and then give them the beta

853
00:36:22,310 --> 00:36:20,520
blocker if you just make them feel like

854
00:36:23,990 --> 00:36:22,320
oh I need to be I want to have this so

855
00:36:24,829 --> 00:36:24,000
much then remove it take the beta

856
00:36:27,829 --> 00:36:24,839
blocker

857
00:36:31,609 --> 00:36:27,839
as this last uh and that makes it very

858
00:36:34,550 --> 00:36:31,619
hard so the uh because so we first years

859
00:36:37,970 --> 00:36:34,560
ago we already tested this with students

860
00:36:40,190 --> 00:36:37,980
that wanted to quit smoking and then we

861
00:36:42,050 --> 00:36:40,200
so we asked them to bring their favorite

862
00:36:44,150 --> 00:36:42,060
cigarettes to the lab

863
00:36:46,130 --> 00:36:44,160
and they thought well I'm smoking my

864
00:36:48,589 --> 00:36:46,140
last cigarette and then they had to give

865
00:36:50,089 --> 00:36:48,599
cigarette to the experimenter and we

866
00:36:53,150 --> 00:36:50,099
were a bit afraid that

867
00:36:55,130 --> 00:36:53,160
that the participants would sort of clap

868
00:36:57,530 --> 00:36:55,140
the experimenter in his face or whatever

869
00:36:59,510 --> 00:36:57,540
but that didn't happen but the treatment

870
00:37:02,690 --> 00:36:59,520
also didn't work and we realized

871
00:37:04,849 --> 00:37:02,700
afterwards yeah because then it is a

872
00:37:07,550 --> 00:37:04,859
sort of passive process in terms of the

873
00:37:08,870 --> 00:37:07,560
memory because someone else decides for

874
00:37:11,150 --> 00:37:08,880
you even though

875
00:37:13,130 --> 00:37:11,160
the participants were motivated to quit

876
00:37:22,550 --> 00:37:13,140
the

877
00:37:25,910 --> 00:37:22,560
we think indeed what you said somehow we

878
00:37:28,310 --> 00:37:25,920
have to trigger the urge to smoke and

879
00:37:30,890 --> 00:37:28,320
then they have to decide themselves so

880
00:37:32,589 --> 00:37:30,900
they really should be engaged in it okay

881
00:37:38,150 --> 00:37:32,599
now

882
00:37:42,829 --> 00:37:40,069
see this is why it's Nobel prize winning

883
00:37:44,990 --> 00:37:42,839
because if this works this can work for

884
00:37:46,970 --> 00:37:45,000
addiction is a huge huge topic this can

885
00:37:49,069 --> 00:37:46,980
work for porn addiction or drug

886
00:37:50,450 --> 00:37:49,079
addiction or any form of addiction I

887
00:37:52,670 --> 00:37:50,460
don't know the limitations but I'm just

888
00:37:55,310 --> 00:37:52,680
surviving yeah well I mean the

889
00:37:57,349 --> 00:37:55,320
translation is so difficult so uh and

890
00:38:00,170 --> 00:37:57,359
there are so I mean it really depends on

891
00:38:01,910 --> 00:38:00,180
so many subtle uh factors whether it

892
00:38:04,130 --> 00:38:01,920
works or not that is I mean as a

893
00:38:06,290 --> 00:38:04,140
scientist that just really I mean I love

894
00:38:10,190 --> 00:38:06,300
that because it's it will never be

895
00:38:12,470 --> 00:38:10,200
boring uh but I'm I'm working at two

896
00:38:14,210 --> 00:38:12,480
sides so I'm a neuroscientist but I'm

897
00:38:17,089 --> 00:38:14,220
also working in clinical science so I

898
00:38:19,849 --> 00:38:17,099
also see the yeah how difficult it is to

899
00:38:22,430 --> 00:38:19,859
bridge these two fields and yeah we are

900
00:38:24,829 --> 00:38:22,440
working on it with a team of PhD

901
00:38:27,890 --> 00:38:24,839
students and postdocs

902
00:38:29,810 --> 00:38:27,900
uh there are also uh I mean there are

903
00:38:32,930 --> 00:38:29,820
several labs in the worlds that

904
00:38:36,470 --> 00:38:32,940
basically work with animal models we can

905
00:38:38,510 --> 00:38:36,480
learn a lot from then because they can

906
00:38:40,069 --> 00:38:38,520
do things that we can't do I mean they

907
00:38:43,069 --> 00:38:40,079
really

908
00:38:45,650 --> 00:38:43,079
and study the microbiology in the brain

909
00:38:48,109 --> 00:38:45,660
and we can study that in humans but uh

910
00:38:52,250 --> 00:38:48,119
yeah the the

911
00:38:54,770 --> 00:38:52,260
it it looks easier I think than it is

912
00:38:56,569 --> 00:38:54,780
and this really has to do so so because

913
00:38:58,970 --> 00:38:56,579
these memories these emotional memories

914
00:39:00,770 --> 00:38:58,980
are so strong also for addiction and

915
00:39:02,329 --> 00:39:00,780
they're

916
00:39:04,670 --> 00:39:02,339
um

917
00:39:08,569 --> 00:39:06,530
I mean if an emotional memory in general

918
00:39:10,310 --> 00:39:08,579
is already strong and then they are

919
00:39:12,170 --> 00:39:10,320
engraved almost in the physical

920
00:39:14,270 --> 00:39:12,180
architecture of the brain especially

921
00:39:16,130 --> 00:39:14,280
because people are addicted for years

922
00:39:18,770 --> 00:39:16,140
they have experienced their Addiction in

923
00:39:22,430 --> 00:39:18,780
many different contexts so it's not easy

924
00:39:24,770 --> 00:39:22,440
to destabilize the memory but yeah

925
00:39:26,930 --> 00:39:24,780
now that we are on there well then we

926
00:39:29,089 --> 00:39:26,940
should be able to change it

927
00:39:31,250 --> 00:39:29,099
now that we are on the cusp of removing

928
00:39:33,589 --> 00:39:31,260
fears I think it might be important to

929
00:39:36,829 --> 00:39:33,599
ask is there an important reason why

930
00:39:40,069 --> 00:39:36,839
people feel fear is what would be the

931
00:39:41,390 --> 00:39:40,079
ramifications of a society that has gone

932
00:39:43,490 --> 00:39:41,400
through with this research and

933
00:39:45,770 --> 00:39:43,500
eliminated not only fear but as you have

934
00:39:47,630 --> 00:39:45,780
mentioned addiction discussed uh even

935
00:39:50,170 --> 00:39:47,640
pleasure towards certain things that are

936
00:39:53,810 --> 00:39:50,180
otherwise unsavory what would the rare

937
00:39:56,950 --> 00:39:53,820
notifications be I think that one that

938
00:40:01,190 --> 00:39:56,960
fear is one of the most uh important

939
00:40:03,349 --> 00:40:01,200
emotions across species

940
00:40:06,609 --> 00:40:03,359
um because it's yeah it definitely

941
00:40:09,050 --> 00:40:06,619
helped us to survive so not only the

942
00:40:13,550 --> 00:40:09,060
it's crucial for the survival of the

943
00:40:20,870 --> 00:40:14,450
um

944
00:40:24,890 --> 00:40:23,030
I was going to ask as a follow-up to

945
00:40:27,950 --> 00:40:24,900
that how far down the phylogenetic tree

946
00:40:30,410 --> 00:40:27,960
does Fear go you know how conserved is

947
00:40:33,290 --> 00:40:30,420
this emotion yeah well it depends a bit

948
00:40:35,690 --> 00:40:33,300
on the definition of fear but if if we

949
00:40:38,210 --> 00:40:35,700
consider defensive reflexes as a sign of

950
00:40:41,870 --> 00:40:38,220
fear then all animals

951
00:40:45,470 --> 00:40:41,880
I think exhibits a signs of fear but I

952
00:40:49,190 --> 00:40:45,480
would say a society without fear well

953
00:40:50,329 --> 00:40:49,200
would not be a society anymore

954
00:40:52,790 --> 00:40:50,339
um

955
00:40:55,790 --> 00:40:52,800
it's also for instance and and the fear

956
00:40:59,990 --> 00:40:55,800
of losing your Offspring it's very

957
00:41:04,670 --> 00:41:00,000
fundamental for our intense

958
00:41:11,530 --> 00:41:08,030
but without fear I mean people should I

959
00:41:16,790 --> 00:41:11,540
I mean I think social behavior is also

960
00:41:21,470 --> 00:41:19,790
sorry if I may if I just briefly go back

961
00:41:23,450 --> 00:41:21,480
to the idea of psychedelics because that

962
00:41:26,390 --> 00:41:23,460
that area really fascinates Me overall

963
00:41:28,910 --> 00:41:26,400
and is there a particular reason uh you

964
00:41:31,130 --> 00:41:28,920
brought up MDMA specifically as opposed

965
00:41:34,430 --> 00:41:31,140
to let's say the other ones such as you

966
00:41:37,550 --> 00:41:34,440
know LSD mushrooms is are there any do

967
00:41:39,890 --> 00:41:37,560
you identify anything specifically speak

968
00:41:40,970 --> 00:41:39,900
to MDMA that is not present in the

969
00:41:43,730 --> 00:41:40,980
others or

970
00:41:45,050 --> 00:41:43,740
well at least I know I'm I I'm not so

971
00:41:46,609 --> 00:41:45,060
familiar with all the streets I know

972
00:41:49,790 --> 00:41:46,619
that there are a couple of studies that

973
00:41:52,970 --> 00:41:49,800
used MDMA successfully in PTSD and and

974
00:41:55,609 --> 00:41:52,980
it's it's it targets The nmda receptors

975
00:41:57,710 --> 00:41:55,619
and nmda receptors are involved in the

976
00:42:00,069 --> 00:41:57,720
memory destabilization so that was

977
00:42:04,130 --> 00:42:00,079
actually the reason that I mentioned

978
00:42:06,290 --> 00:42:04,140
MDMA as far as I can understand the MDMA

979
00:42:08,810 --> 00:42:06,300
would be more for the cognitive

980
00:42:11,089 --> 00:42:08,820
behavioral therapy route where you just

981
00:42:13,250 --> 00:42:11,099
get them to relive their memory and then

982
00:42:14,810 --> 00:42:13,260
now with the MDMA they can't feel the

983
00:42:17,270 --> 00:42:14,820
fear as much in fact they might attach

984
00:42:18,710 --> 00:42:17,280
positive emotions to it whereas with

985
00:42:20,390 --> 00:42:18,720
your treatment it's like please don't

986
00:42:22,310 --> 00:42:20,400
attach any positive emotions Feel the

987
00:42:23,690 --> 00:42:22,320
fear so that's why with LSD that's

988
00:42:25,609 --> 00:42:23,700
completely different LSD it's not like

989
00:42:26,810 --> 00:42:25,619
you're only experiencing Euphoria you

990
00:42:28,430 --> 00:42:26,820
can have the most intense anxiety

991
00:42:29,930 --> 00:42:28,440
attacks of your entire life do you

992
00:42:30,890 --> 00:42:29,940
imagine the treatment with LSD would be

993
00:42:33,290 --> 00:42:30,900
I would imagine it'd be much different

994
00:42:34,970 --> 00:42:33,300
than MDMA I would imagine that LSD or

995
00:42:37,010 --> 00:42:34,980
mushrooms would be more in line with

996
00:42:38,270 --> 00:42:37,020
your treatment rather than MDMA which is

997
00:42:40,190 --> 00:42:38,280
a cognitive behavioral therapy

998
00:42:42,589 --> 00:42:40,200
accelerators MDMA your treatment

999
00:42:43,730 --> 00:42:42,599
accelerator might be the LSD that's what

1000
00:42:45,710 --> 00:42:43,740
I surmise but I want to know what you

1001
00:42:49,190 --> 00:42:45,720
think

1002
00:42:50,569 --> 00:42:49,200
yeah I agree because

1003
00:42:52,490 --> 00:42:50,579
uh yeah

1004
00:42:54,890 --> 00:42:52,500
MDMA

1005
00:42:58,430 --> 00:42:54,900
triggers and I think an oxytociner

1006
00:43:00,950 --> 00:42:58,440
release if I yeah

1007
00:43:06,470 --> 00:43:03,890
so it could be sort of somehow inhibits

1008
00:43:09,470 --> 00:43:06,480
the um it could work in two directions

1009
00:43:11,690 --> 00:43:09,480
because it could also help if you feel

1010
00:43:14,150 --> 00:43:11,700
safe and attached for instance to your

1011
00:43:16,730 --> 00:43:14,160
therapist it could also help to dive

1012
00:43:19,670 --> 00:43:16,740
into your also in

1013
00:43:22,329 --> 00:43:19,680
into the trauma memory and into the more

1014
00:43:26,150 --> 00:43:22,339
difficult emotions so in that sense

1015
00:43:28,910 --> 00:43:26,160
MDMA would also work

1016
00:43:30,650 --> 00:43:28,920
because if you are too if the emotions

1017
00:43:32,470 --> 00:43:30,660
are too strong it could also add a

1018
00:43:36,650 --> 00:43:32,480
certain important sort of yeah

1019
00:43:39,530 --> 00:43:36,660
inhibits of really going into into it

1020
00:43:41,390 --> 00:43:39,540
and feeling it the documentary you

1021
00:43:43,010 --> 00:43:41,400
mentioned is called cure of fear is that

1022
00:43:44,990 --> 00:43:43,020
correct yeah

1023
00:43:47,569 --> 00:43:45,000
okay I recommend everyone watch this

1024
00:43:49,130 --> 00:43:47,579
this I watched it I found it endlessly

1025
00:43:50,630 --> 00:43:49,140
fascinating is what turned me on to your

1026
00:43:52,130 --> 00:43:50,640
research to begin with

1027
00:43:54,530 --> 00:43:52,140
is there something else you do

1028
00:43:56,210 --> 00:43:54,540
afterwards after the post for your

1029
00:43:57,770 --> 00:43:56,220
stimulus other than just giving them the

1030
00:43:59,569 --> 00:43:57,780
beta blocker do you talk them down do

1031
00:44:01,309 --> 00:43:59,579
you say everything will be okay or is it

1032
00:44:03,170 --> 00:44:01,319
as simple as expose yourself to the fear

1033
00:44:04,370 --> 00:44:03,180
10 out of 10 take the beta blocker five

1034
00:44:06,589 --> 00:44:04,380
minutes after that or pretty much

1035
00:44:08,270 --> 00:44:06,599
immediately after that and go along with

1036
00:44:12,290 --> 00:44:08,280
your day have a nice rest is there

1037
00:44:14,510 --> 00:44:12,300
something else that's missing no so so

1038
00:44:16,849 --> 00:44:14,520
I mean the the exposure it's it's it's

1039
00:44:18,950 --> 00:44:16,859
not so easy I mean that is really

1040
00:44:20,809 --> 00:44:18,960
difficult people are generally not able

1041
00:44:22,550 --> 00:44:20,819
to do it themselves because they really

1042
00:44:25,790 --> 00:44:22,560
need support

1043
00:44:29,210 --> 00:44:25,800
to actually do it because the fear

1044
00:44:31,910 --> 00:44:29,220
response itself triggers an an avoidance

1045
00:44:34,010 --> 00:44:31,920
response so they want to to escape the

1046
00:44:37,010 --> 00:44:34,020
situation of course but if they have

1047
00:44:39,109 --> 00:44:37,020
done so no then they go to a room uh

1048
00:44:39,950 --> 00:44:39,119
what we do is

1049
00:44:43,970 --> 00:44:39,960
um

1050
00:44:46,730 --> 00:44:43,980
only I mean I briefly reinforce them for

1051
00:44:50,450 --> 00:44:46,740
what they did so far and then they wait

1052
00:44:52,609 --> 00:44:50,460
for two hours they relax uh because we

1053
00:44:55,190 --> 00:44:52,619
want to make sure that they

1054
00:44:56,809 --> 00:44:55,200
don't have another stressful experience

1055
00:44:59,569 --> 00:44:56,819
that could trigger another nor

1056
00:45:02,270 --> 00:44:59,579
adrenaline response it could interfere

1057
00:45:04,609 --> 00:45:02,280
with the effect of the beta blocker and

1058
00:45:06,589 --> 00:45:04,619
then after two hours they go home have a

1059
00:45:09,410 --> 00:45:06,599
night of sleep and then they come back

1060
00:45:11,870 --> 00:45:09,420
for a test

1061
00:45:13,910 --> 00:45:11,880
so you're there in part to make sure

1062
00:45:15,710 --> 00:45:13,920
that they don't have another traumatic

1063
00:45:17,089 --> 00:45:15,720
experience that worsens it completely

1064
00:45:19,490 --> 00:45:17,099
because I would imagine that this could

1065
00:45:21,290 --> 00:45:19,500
drive someone insane if they're exposed

1066
00:45:23,930 --> 00:45:21,300
to 10 out of 10 of fear on something

1067
00:45:27,410 --> 00:45:23,940
that they're already extremely afraid of

1068
00:45:29,990 --> 00:45:27,420
yeah so uh so we we try to make sure

1069
00:45:31,250 --> 00:45:30,000
that they are not re-exposed to uh to

1070
00:45:32,930 --> 00:45:31,260
the field queue and sometimes it's

1071
00:45:34,609 --> 00:45:32,940
difficult for instance we also treat

1072
00:45:36,230 --> 00:45:34,619
people with fear of dogs and then when

1073
00:45:39,109 --> 00:45:36,240
they go outside it could be that they

1074
00:45:41,329 --> 00:45:39,119
will meet a dog again and yeah because

1075
00:45:44,270 --> 00:45:41,339
then because we know that I mean that

1076
00:45:46,250 --> 00:45:44,280
could trigger again the fear memory and

1077
00:45:47,870 --> 00:45:46,260
we don't know but it makes sense that it

1078
00:45:50,089 --> 00:45:47,880
then interferes with the treatment

1079
00:45:52,490 --> 00:45:50,099
effect so we always make sure if that is

1080
00:45:55,010 --> 00:45:52,500
the case that someone will pick them up

1081
00:45:57,050 --> 00:45:55,020
in the car that they don't meet a dog

1082
00:45:57,890 --> 00:45:57,060
until a night of sleep and then the next

1083
00:46:00,829 --> 00:45:57,900
day

1084
00:46:03,890 --> 00:46:00,839
so we also once treated a woman with a

1085
00:46:06,109 --> 00:46:03,900
fear of silverfish and they were at her

1086
00:46:09,890 --> 00:46:06,119
house so she was not allowed to sleep in

1087
00:46:11,930 --> 00:46:09,900
her own house she she booked a hotel and

1088
00:46:15,230 --> 00:46:11,940
then came back for the test and then

1089
00:46:18,589 --> 00:46:15,240
after this first night she could go home

1090
00:46:22,130 --> 00:46:18,599
again to to expose herself to the

1091
00:46:24,650 --> 00:46:22,140
silverfish when she was removed from the

1092
00:46:26,510 --> 00:46:24,660
fear now in this case of the silverfish

1093
00:46:27,650 --> 00:46:26,520
was there a traumatic event that

1094
00:46:29,270 --> 00:46:27,660
happened that made her afraid of the

1095
00:46:31,190 --> 00:46:29,280
silverfish to begin with excuse me for

1096
00:46:33,589 --> 00:46:31,200
seeming imbecile grass and I I have a

1097
00:46:35,870 --> 00:46:33,599
fear and it's a flying insect I despise

1098
00:46:37,910 --> 00:46:35,880
flying insects like I like dragonflies

1099
00:46:40,490 --> 00:46:37,920
it's the only kind but mosquitoes and

1100
00:46:41,750 --> 00:46:40,500
bees and black flies I I can't even go

1101
00:46:44,030 --> 00:46:41,760
into the Wilderness because of it

1102
00:46:45,530 --> 00:46:44,040
practically speaking

1103
00:46:48,770 --> 00:46:45,540
I don't have access to I'm not in

1104
00:46:51,230 --> 00:46:48,780
Amsterdam what can I do here in Toronto

1105
00:46:52,670 --> 00:46:51,240
alone in my condo and other people who

1106
00:46:54,530 --> 00:46:52,680
have fears similar to mines maybe not

1107
00:46:56,510 --> 00:46:54,540
flying insects but what can they do No

1108
00:46:58,550 --> 00:46:56,520
One's Gonna sue you what would you what

1109
00:47:00,530 --> 00:46:58,560
would you do

1110
00:47:02,930 --> 00:47:00,540
yeah what I would do is expose you then

1111
00:47:04,670 --> 00:47:02,940
I would first ask you which if if there

1112
00:47:07,250 --> 00:47:04,680
is an insect that you

1113
00:47:07,910 --> 00:47:07,260
um fear most and then order

1114
00:47:09,069 --> 00:47:07,920
um

1115
00:47:12,130 --> 00:47:09,079
yeah

1116
00:47:14,270 --> 00:47:12,140
a couple of them or sometimes doesn't

1117
00:47:18,230 --> 00:47:14,280
and then

1118
00:47:19,550 --> 00:47:18,240
um so very often Fierce so first of all

1119
00:47:21,230 --> 00:47:19,560
your first question was actually is it

1120
00:47:24,290 --> 00:47:21,240
necessary to have a traumatic experience

1121
00:47:25,730 --> 00:47:24,300
with the cue that you fear no the idea

1122
00:47:28,250 --> 00:47:25,740
is so at least it is our

1123
00:47:30,470 --> 00:47:28,260
conceptualization of fear and anxiety

1124
00:47:32,630 --> 00:47:30,480
disorders that there isn't we call fear

1125
00:47:34,670 --> 00:47:32,640
memory or associate memory that analyzed

1126
00:47:37,130 --> 00:47:34,680
the fear response and the fear memory is

1127
00:47:39,770 --> 00:47:37,140
formed either through direct traumatic

1128
00:47:41,690 --> 00:47:39,780
experiences but also very often in an

1129
00:47:43,010 --> 00:47:41,700
indirect way just by modeling because

1130
00:47:46,130 --> 00:47:43,020
you have seen other people that are

1131
00:47:48,410 --> 00:47:46,140
afraid of dogs or insects or by

1132
00:47:50,690 --> 00:47:48,420
information or sometimes people really

1133
00:47:52,609 --> 00:47:50,700
don't know how they developed it but it

1134
00:47:56,450 --> 00:47:52,619
is just there then

1135
00:47:58,609 --> 00:47:56,460
if you have a fear some people have some

1136
00:48:01,130 --> 00:47:58,619
sort of traumatic experience because if

1137
00:48:02,750 --> 00:48:01,140
you have a fear of a specific animal and

1138
00:48:07,309 --> 00:48:02,760
that you are exposed to the animal that

1139
00:48:11,329 --> 00:48:08,870
um

1140
00:48:12,430 --> 00:48:11,339
for your treatment then yeah I would say

1141
00:48:14,569 --> 00:48:12,440
well

1142
00:48:18,410 --> 00:48:14,579
we should

1143
00:48:20,270 --> 00:48:18,420
try to I mean I first I should do a sort

1144
00:48:23,510 --> 00:48:20,280
of interview to know exactly what kind

1145
00:48:25,910 --> 00:48:23,520
of situation would be terrifying for you

1146
00:48:29,569 --> 00:48:25,920
like being in a small room for instance

1147
00:48:32,210 --> 00:48:29,579
with insects or that that they that you

1148
00:48:34,370 --> 00:48:32,220
that they are on your skin or on your

1149
00:48:36,410 --> 00:48:34,380
feet or whatever so at first I'm not

1150
00:48:38,510 --> 00:48:36,420
claustrophobic but yes if I was in a

1151
00:48:41,030 --> 00:48:38,520
room that's trapped with a thousand

1152
00:48:43,430 --> 00:48:41,040
mosquitoes I dislike the buzzing around

1153
00:48:44,630 --> 00:48:43,440
my ears so I imagine maybe I can't order

1154
00:48:45,890 --> 00:48:44,640
mosquitoes I don't even know how you can

1155
00:48:47,390 --> 00:48:45,900
do that maybe I could just find a

1156
00:48:49,130 --> 00:48:47,400
YouTube video of mosquitoes around a

1157
00:48:51,410 --> 00:48:49,140
microphone put that on try to imagine

1158
00:48:53,089 --> 00:48:51,420
myself in a room full of mosquitoes

1159
00:48:54,290 --> 00:48:53,099
make my fear response four out of ten

1160
00:48:55,910 --> 00:48:54,300
because that's probably the best I could

1161
00:48:57,170 --> 00:48:55,920
do then take the beta blocker do you

1162
00:49:00,109 --> 00:48:57,180
imagine something like that would work

1163
00:49:02,569 --> 00:49:00,119
no I don't think so it's not enough I

1164
00:49:04,849 --> 00:49:02,579
think just hearing it and and not being

1165
00:49:07,130 --> 00:49:04,859
exposed to the real threat

1166
00:49:10,130 --> 00:49:07,140
yeah and it is probably to do something

1167
00:49:12,290 --> 00:49:10,140
because most of the fears in

1168
00:49:15,470 --> 00:49:12,300
have to do with not being able to

1169
00:49:18,230 --> 00:49:15,480
predict for instance the the cue that

1170
00:49:21,230 --> 00:49:18,240
you fear and with not being able to

1171
00:49:23,510 --> 00:49:21,240
control it so with uncontrollability and

1172
00:49:26,870 --> 00:49:23,520
with unpredictability and that's why

1173
00:49:29,990 --> 00:49:26,880
these insects moving fast and somehow

1174
00:49:32,030 --> 00:49:30,000
yeah you feel probably like I I want to

1175
00:49:34,730 --> 00:49:32,040
control them I want to control the the

1176
00:49:36,470 --> 00:49:34,740
noise or that they come to me and you

1177
00:49:41,690 --> 00:49:36,480
can't so this is really then what you

1178
00:49:47,089 --> 00:49:41,700
need in the treatment to feel that uh

1179
00:49:48,530 --> 00:49:47,099
in order to Target your fear memory

1180
00:49:52,130 --> 00:49:48,540
so what compelled you to make this

1181
00:49:54,530 --> 00:49:52,140
documentary the peer to fear documentary

1182
00:49:57,050 --> 00:49:54,540
yeah first of all uh the documentary

1183
00:49:59,510 --> 00:49:57,060
there are more documentaries so first

1184
00:50:03,170 --> 00:49:59,520
the memory hackers and there's a

1185
00:50:04,849 --> 00:50:03,180
treatment uh uh was a nofa documentary

1186
00:50:07,609 --> 00:50:04,859
and then this

1187
00:50:10,130 --> 00:50:07,619
um the science of fear by Roberto

1188
00:50:12,349 --> 00:50:10,140
fredekia that is uh

1189
00:50:16,309 --> 00:50:12,359
be afraid to the science of fear that

1190
00:50:18,230 --> 00:50:16,319
was broadcasted in Canada actually

1191
00:50:20,510 --> 00:50:18,240
CBS

1192
00:50:22,210 --> 00:50:20,520
um they approached me so not a vice

1193
00:50:26,450 --> 00:50:22,220
versa

1194
00:50:28,490 --> 00:50:26,460
and the same old for Lana Wilson uh but

1195
00:50:29,930 --> 00:50:28,500
yeah

1196
00:50:31,250 --> 00:50:29,940
I think

1197
00:50:37,069 --> 00:50:31,260
um

1198
00:50:39,530 --> 00:50:37,079
to first to educate people that uh that

1199
00:50:42,290 --> 00:50:39,540
that there are millions of people that

1200
00:50:46,069 --> 00:50:42,300
suffer from crippling fears and phobias

1201
00:50:48,410 --> 00:50:46,079
so to to to teach people that they are

1202
00:50:51,230 --> 00:50:48,420
not weak or crazy that they have these

1203
00:50:53,690 --> 00:50:51,240
fears that that is very important but

1204
00:50:55,970 --> 00:50:53,700
also to educate them about or the

1205
00:50:59,530 --> 00:50:55,980
mysteries of emotional memory which is I

1206
00:51:04,430 --> 00:50:59,540
think for everyone a very relevant and

1207
00:51:08,990 --> 00:51:06,950
great um I'd like to ask a couple of

1208
00:51:10,910 --> 00:51:09,000
technical questions if I may um

1209
00:51:13,430 --> 00:51:10,920
regarding your research and you're

1210
00:51:17,030 --> 00:51:13,440
Illuminating 2009 paper and you briefly

1211
00:51:18,829 --> 00:51:17,040
discussed two theories uh namely uh you

1212
00:51:20,750 --> 00:51:18,839
know the there was the storage Theory as

1213
00:51:22,970 --> 00:51:20,760
well as the retrieval Theory one of

1214
00:51:26,089 --> 00:51:22,980
which you survives may have caused a

1215
00:51:28,490 --> 00:51:26,099
fair memory Extinction however at the

1216
00:51:31,910 --> 00:51:28,500
time it was not clear which one was the

1217
00:51:33,650 --> 00:51:31,920
cause would you please a little bit

1218
00:51:35,870 --> 00:51:33,660
elaborate on these theories and

1219
00:51:38,750 --> 00:51:35,880
furthermore tell us whether 11 years

1220
00:51:40,549 --> 00:51:38,760
later now in 2020 do we have a better

1221
00:51:42,710 --> 00:51:40,559
understanding of the mechanism behind

1222
00:51:45,170 --> 00:51:42,720
memory Extinction from a let's say

1223
00:51:49,190 --> 00:51:45,180
theoretical perspective or is it still

1224
00:51:52,970 --> 00:51:49,200
largely a mystery overall no well

1225
00:51:55,549 --> 00:51:52,980
if you only study human

1226
00:51:57,650 --> 00:51:55,559
almost at least for your heart and

1227
00:51:59,390 --> 00:51:57,660
almost impossible to to disentangle

1228
00:52:02,390 --> 00:51:59,400
between a retrieval

1229
00:52:04,490 --> 00:52:02,400
problem or storage problem whether you

1230
00:52:06,290 --> 00:52:04,500
really change the underlying memory

1231
00:52:08,089 --> 00:52:06,300
trace or whether you it's difficult it's

1232
00:52:10,190 --> 00:52:08,099
more difficult to retrieve it but maybe

1233
00:52:12,910 --> 00:52:10,200
it is still there but you can just

1234
00:52:16,370 --> 00:52:12,920
retrieve it and

1235
00:52:20,329 --> 00:52:16,380
clinically I mean if the retrieval

1236
00:52:21,770 --> 00:52:20,339
uh difficulty is is so huge that you can

1237
00:52:24,349 --> 00:52:21,780
never retrieve it anymore then it

1238
00:52:25,730 --> 00:52:24,359
doesn't make any difference but

1239
00:52:27,890 --> 00:52:25,740
theoretically it's of course very

1240
00:52:30,710 --> 00:52:27,900
interesting from the animal literature

1241
00:52:32,210 --> 00:52:30,720
well now that we are more and more able

1242
00:52:35,329 --> 00:52:32,220
to

1243
00:52:36,349 --> 00:52:35,339
find actually the memory engram in the

1244
00:52:39,410 --> 00:52:36,359
brain

1245
00:52:42,410 --> 00:52:39,420
by optogenetics and so on and that means

1246
00:52:44,049 --> 00:52:42,420
that you can turn on and off the fear

1247
00:52:46,790 --> 00:52:44,059
memory

1248
00:52:49,849 --> 00:52:46,800
they also showed that the

1249
00:52:52,790 --> 00:52:49,859
reconsolidation intervention really

1250
00:52:55,370 --> 00:52:52,800
changed the memory engram and this

1251
00:52:57,710 --> 00:52:55,380
suggests at least that it affects the

1252
00:52:58,549 --> 00:52:57,720
storage of the fear memory and that is

1253
00:53:01,569 --> 00:52:58,559
not

1254
00:53:04,609 --> 00:53:01,579
just a retrieval issue

1255
00:53:05,990 --> 00:53:04,619
okay so from the animal side then it's

1256
00:53:07,670 --> 00:53:06,000
it's more geared toward the storage

1257
00:53:11,089 --> 00:53:07,680
aspect yeah

1258
00:53:15,170 --> 00:53:11,099
purely based on human research I read it

1259
00:53:17,809 --> 00:53:15,180
to this actually yeah impossible to uh

1260
00:53:19,849 --> 00:53:17,819
this entangle the two uh conceptual

1261
00:53:22,309 --> 00:53:19,859
Frameworks yeah right yes there are

1262
00:53:25,069 --> 00:53:22,319
limitations unfortunately and um going

1263
00:53:26,870 --> 00:53:25,079
back to the imagery rescripting uh

1264
00:53:29,510 --> 00:53:26,880
phenomenon that you had you I think you

1265
00:53:31,609 --> 00:53:29,520
delved deep into it into a recent 2019

1266
00:53:33,650 --> 00:53:31,619
paper where you discuss you know the

1267
00:53:36,530 --> 00:53:33,660
role of imagery scripting in emotional

1268
00:53:38,329 --> 00:53:36,540
memory now maybe if we can just briefly

1269
00:53:41,630 --> 00:53:38,339
talk about this a little more just to

1270
00:53:43,549 --> 00:53:41,640
see whether you know we could utilize

1271
00:53:47,390 --> 00:53:43,559
imagery scripting in conjunction with

1272
00:53:50,030 --> 00:53:47,400
with let's say Propranolol uh to extend

1273
00:53:52,490 --> 00:53:50,040
the impact of modifying fear in various

1274
00:53:54,470 --> 00:53:52,500
settings for example online therapies

1275
00:53:56,089 --> 00:53:54,480
like is that a possibility you think I

1276
00:53:58,849 --> 00:53:56,099
mean we I know we briefly talked about

1277
00:54:00,829 --> 00:53:58,859
how the fear has to you we have to be in

1278
00:54:02,930 --> 00:54:00,839
a controlled environment where this has

1279
00:54:05,329 --> 00:54:02,940
to be properly conducted but with the

1280
00:54:07,490 --> 00:54:05,339
introduction of imagery restricting do

1281
00:54:09,890 --> 00:54:07,500
you think we can do anything in that

1282
00:54:16,460 --> 00:54:09,900
regard or or no we still have certain

1283
00:54:22,010 --> 00:54:19,130
[Music]

1284
00:54:22,970 --> 00:54:22,020
I think that for instance in for if when

1285
00:54:27,170 --> 00:54:22,980
we

1286
00:54:29,650 --> 00:54:27,180
um use the procedure in specific fears

1287
00:54:31,930 --> 00:54:29,660
and phobias but we actually asked the

1288
00:54:35,150 --> 00:54:31,940
participant to

1289
00:54:38,030 --> 00:54:35,160
approach for instance the spider or the

1290
00:54:40,609 --> 00:54:38,040
dog and and then I mean

1291
00:54:43,010 --> 00:54:40,619
usually they would sort of uh run away

1292
00:54:45,470 --> 00:54:43,020
because I think if I approach it then

1293
00:54:47,930 --> 00:54:45,480
something very bad happens and then they

1294
00:54:49,910 --> 00:54:47,940
experience that it doesn't happen

1295
00:54:51,950 --> 00:54:49,920
so this is sort of new something new

1296
00:54:54,049 --> 00:54:51,960
it's a new experience and that's the

1297
00:54:57,190 --> 00:54:54,059
idea is that this is necessary to open

1298
00:55:00,290 --> 00:54:57,200
up the memory Trace

1299
00:55:03,109 --> 00:55:00,300
uh and for trauma memory it could be

1300
00:55:05,690 --> 00:55:03,119
that especially sometimes you we see uh

1301
00:55:08,150 --> 00:55:05,700
traumatized people and they went over

1302
00:55:10,609 --> 00:55:08,160
and over the trauma memory and the

1303
00:55:12,470 --> 00:55:10,619
trauma story and then it's really hard

1304
00:55:16,069 --> 00:55:12,480
just by going back

1305
00:55:17,510 --> 00:55:16,079
to to open up the memory trace and do

1306
00:55:20,890 --> 00:55:17,520
and then when we do a little bit of

1307
00:55:25,490 --> 00:55:20,900
restricting it could help to destabilize

1308
00:55:29,990 --> 00:55:27,950
right so so in a sense it is possible

1309
00:55:32,329 --> 00:55:30,000
then to do something in conjunction

1310
00:55:34,309 --> 00:55:32,339
with because I know in that study you

1311
00:55:38,270 --> 00:55:34,319
did not introduce beta blockers right it

1312
00:55:41,030 --> 00:55:38,280
was purely yeah well or so then so we we

1313
00:55:42,829 --> 00:55:41,040
did it we over edit this already so a

1314
00:55:47,569 --> 00:55:42,839
couple of times then it's only one

1315
00:55:51,349 --> 00:55:47,579
session but I also supervised several uh

1316
00:55:54,530 --> 00:55:51,359
um so a recent uh huge trial and also in

1317
00:55:56,630 --> 00:55:54,540
the in the past trial uh where we only

1318
00:55:58,670 --> 00:55:56,640
did imagery scripting but then it's more

1319
00:56:01,490 --> 00:55:58,680
like a traditional cognitive behavior

1320
00:56:04,430 --> 00:56:01,500
treatment and you do sort of weekly uh

1321
00:56:07,549 --> 00:56:04,440
sessions many sessions in a row

1322
00:56:12,530 --> 00:56:07,559
right right right yeah okay my question

1323
00:56:15,530 --> 00:56:12,540
on disgust is is it possible to

1324
00:56:18,589 --> 00:56:15,540
have a technique for disgust that would

1325
00:56:21,829 --> 00:56:18,599
eliminate it and mirror would it be the

1326
00:56:26,089 --> 00:56:21,839
same process except as as fear removal

1327
00:56:28,250 --> 00:56:26,099
but instead with the disgusting stimulus

1328
00:56:30,530 --> 00:56:28,260
so for example uh if someone is

1329
00:56:33,290 --> 00:56:30,540
completely grossed out by by blood or by

1330
00:56:36,349 --> 00:56:33,300
public toilets uh how would they

1331
00:56:39,710 --> 00:56:36,359
overcome this this discuss would they do

1332
00:56:44,390 --> 00:56:41,630
yeah

1333
00:56:50,930 --> 00:56:46,970
I don't know I don't think sometimes we

1334
00:56:53,990 --> 00:56:50,940
see people with a fear of spiders but

1335
00:56:57,530 --> 00:56:54,000
sometimes they also find the spiders

1336
00:57:02,390 --> 00:56:58,549
um

1337
00:57:05,329 --> 00:57:02,400
we have the ID but we never really

1338
00:57:07,790 --> 00:57:05,339
tested it that that's the treatment then

1339
00:57:11,089 --> 00:57:07,800
reduces the fear response but that the

1340
00:57:12,349 --> 00:57:11,099
disgusts remains intact I can imagine

1341
00:57:15,349 --> 00:57:12,359
though

1342
00:57:17,390 --> 00:57:15,359
that if they disgust is that sometimes

1343
00:57:20,809 --> 00:57:17,400
if for instance disgust is so strong

1344
00:57:24,530 --> 00:57:20,819
that people are yeah are afraid of the

1345
00:57:26,809 --> 00:57:24,540
disgusts I mean not two to a degree some

1346
00:57:29,870 --> 00:57:26,819
people have a sort of

1347
00:57:31,849 --> 00:57:29,880
cheese aversion or so or milk aversion

1348
00:57:35,030 --> 00:57:31,859
so they have sort of discussed for some

1349
00:57:36,950 --> 00:57:35,040
smells or and so on and I think by I

1350
00:57:39,109 --> 00:57:36,960
don't think that we can treat that but

1351
00:57:41,809 --> 00:57:39,119
then if people really

1352
00:57:44,870 --> 00:57:41,819
fear that if they are exposed

1353
00:57:46,849 --> 00:57:44,880
to something that would trigger such a

1354
00:57:49,970 --> 00:57:46,859
strong discussed feeling that they will

1355
00:57:53,150 --> 00:57:49,980
faint or whatever we could

1356
00:57:55,849 --> 00:57:53,160
treat that so then the discus is more

1357
00:57:59,510 --> 00:57:55,859
like what a spider or a dog is for

1358
00:58:02,569 --> 00:57:59,520
people with a animal phobia

1359
00:58:04,430 --> 00:58:02,579
I see thank you now before we wrap up I

1360
00:58:06,170 --> 00:58:04,440
have an analogy that I made that I think

1361
00:58:07,609 --> 00:58:06,180
is completely naive and I want you to

1362
00:58:09,170 --> 00:58:07,619
correct it because I couldn't figure out

1363
00:58:10,549 --> 00:58:09,180
a better way of conceptualizing your

1364
00:58:12,470 --> 00:58:10,559
research as to why beta blockers

1365
00:58:13,849 --> 00:58:12,480
afterwards Works rather than before so

1366
00:58:16,609 --> 00:58:13,859
the way that I see it is when you get

1367
00:58:18,049 --> 00:58:16,619
exposed to a fearful stimuli it's as if

1368
00:58:19,970 --> 00:58:18,059
imagine you have a cabinet behind you

1369
00:58:21,650 --> 00:58:19,980
and this is an oversimplification and

1370
00:58:23,750 --> 00:58:21,660
each one of the drawers in the cabinet

1371
00:58:26,210 --> 00:58:23,760
is a memory it's as if what you've done

1372
00:58:27,290 --> 00:58:26,220
in the fear example is you've opened up

1373
00:58:29,510 --> 00:58:27,300
that drawer

1374
00:58:30,890 --> 00:58:29,520
however if you take the beta blockers

1375
00:58:32,390 --> 00:58:30,900
before because I believe memory

1376
00:58:34,010 --> 00:58:32,400
consolidation is highly dependent on

1377
00:58:35,089 --> 00:58:34,020
beta receptors in your brain that if you

1378
00:58:36,770 --> 00:58:35,099
take beta blockers that actually

1379
00:58:38,270 --> 00:58:36,780
interferes with you formulating memories

1380
00:58:39,770 --> 00:58:38,280
so if you were to take the beta blocker

1381
00:58:41,510 --> 00:58:39,780
before it would be as if maybe you open

1382
00:58:43,250 --> 00:58:41,520
up that drawer but the rewrite

1383
00:58:45,349 --> 00:58:43,260
capabilities are not there because the

1384
00:58:47,930 --> 00:58:45,359
beta receptors for some reason need to

1385
00:58:49,670 --> 00:58:47,940
be active for the rewrite abilities to

1386
00:58:51,770 --> 00:58:49,680
be available then you take the beta

1387
00:58:53,870 --> 00:58:51,780
blockers afterwards because it's not as

1388
00:58:55,670 --> 00:58:53,880
if the memory gets rewrote I know this

1389
00:58:58,010 --> 00:58:55,680
is so convoluted it's not as if the

1390
00:58:59,569 --> 00:58:58,020
memory gets Rewritten right then it gets

1391
00:59:01,789 --> 00:58:59,579
Rewritten about two hours later or one

1392
00:59:03,829 --> 00:59:01,799
hour later so it's like fear stimuli

1393
00:59:05,329 --> 00:59:03,839
open up that drawer don't rewrite in it

1394
00:59:06,950 --> 00:59:05,339
wait one hour then the brain is going to

1395
00:59:09,170 --> 00:59:06,960
rewrite it but the brain at one hour

1396
00:59:10,849 --> 00:59:09,180
from now looks to the body how are you

1397
00:59:12,349 --> 00:59:10,859
feeling are you afraid and then it will

1398
00:59:13,789 --> 00:59:12,359
rewrite based on that so that's why if

1399
00:59:15,530 --> 00:59:13,799
you take a beta blocker afterwards and

1400
00:59:17,990 --> 00:59:15,540
you're calm it's like okay we're about

1401
00:59:20,329 --> 00:59:18,000
to rewrite but now I see your com let's

1402
00:59:22,130 --> 00:59:20,339
rewrite it and say calmness let's put

1403
00:59:24,770 --> 00:59:22,140
the hashtag com on it what's wrong with

1404
00:59:26,870 --> 00:59:24,780
that yeah you said a lot first of all I

1405
00:59:30,829 --> 00:59:26,880
think that the the actual rewriting

1406
00:59:36,890 --> 00:59:34,010
um and that's probably the there's more

1407
00:59:39,170 --> 00:59:36,900
work on that probably the face where

1408
00:59:41,510 --> 00:59:39,180
when there's no new incoming information

1409
00:59:43,549 --> 00:59:41,520
it's sort of that for the brain that is

1410
00:59:45,170 --> 00:59:43,559
probably the sort of best face to decide

1411
00:59:47,930 --> 00:59:45,180
if this is the information that should

1412
00:59:49,609 --> 00:59:47,940
be kept and this can be forgotten so

1413
00:59:51,530 --> 00:59:49,619
that makes sense to do that when there

1414
00:59:54,470 --> 00:59:51,540
is no new incoming information that is

1415
00:59:57,589 --> 00:59:54,480
during the night but there are of course

1416
01:00:01,010 --> 00:59:57,599
several important steps in this whole

1417
01:00:02,809 --> 01:00:01,020
process of resetting so the the what we

1418
01:00:05,210 --> 01:00:02,819
have shown is that you should give the

1419
01:00:06,890 --> 01:00:05,220
beta blocker up to one hour after memory

1420
01:00:10,789 --> 01:00:06,900
retrieve and not two hours is probably

1421
01:00:13,190 --> 01:00:10,799
because in this in this brief window

1422
01:00:14,510 --> 01:00:13,200
time window the beta generic receptors

1423
01:00:15,589 --> 01:00:14,520
are involved but there are of course

1424
01:00:18,170 --> 01:00:15,599
many other

1425
01:00:21,230 --> 01:00:18,180
steps in this whole Cascade of memory

1426
01:00:24,710 --> 01:00:21,240
resaving but the actually writing

1427
01:00:28,730 --> 01:00:25,490
um

1428
01:00:32,030 --> 01:00:28,740
I think in the in the lab when we did a

1429
01:00:34,670 --> 01:00:32,040
fair conditioning and we do not measure

1430
01:00:37,069 --> 01:00:34,680
freezing what they do in rodents but we

1431
01:00:38,690 --> 01:00:37,079
measure the start or reflect this is I

1432
01:00:39,950 --> 01:00:38,700
blink reflex

1433
01:00:42,530 --> 01:00:39,960
so

1434
01:00:46,010 --> 01:00:42,540
um this is uh yeah you cannot control

1435
01:00:48,829 --> 01:00:46,020
this reflex it's a defensive reflex

1436
01:00:50,870 --> 01:00:48,839
um initiated in the Amica lab and that

1437
01:00:52,250 --> 01:00:50,880
is typically potentiated when people

1438
01:00:53,630 --> 01:00:52,260
anticipate

1439
01:00:56,089 --> 01:00:53,640
something

1440
01:00:58,849 --> 01:00:56,099
threatening so when they are in a

1441
01:01:01,010 --> 01:00:58,859
fearful State you see an enhanced

1442
01:01:05,210 --> 01:01:01,020
startle

1443
01:01:06,010 --> 01:01:05,220
about reflex startup position

1444
01:01:07,690 --> 01:01:06,020
um

1445
01:01:10,970 --> 01:01:07,700
[Music]

1446
01:01:13,789 --> 01:01:10,980
this uh defense of fear Behavior was not

1447
01:01:16,309 --> 01:01:13,799
suppressed when we gave Propranolol

1448
01:01:18,109 --> 01:01:16,319
before memory retrieval

1449
01:01:19,490 --> 01:01:18,119
so

1450
01:01:27,589 --> 01:01:19,500
and

1451
01:01:30,650 --> 01:01:27,599
apparently targeted the the beta genetic

1452
01:01:34,130 --> 01:01:30,660
receptors in in the phase where it shoot

1453
01:01:36,890 --> 01:01:34,140
if you do it if you give propanolol

1454
01:01:39,470 --> 01:01:36,900
um to people that suffer from that that

1455
01:01:40,370 --> 01:01:39,480
suffer from a phobia

1456
01:01:43,789 --> 01:01:40,380
um

1457
01:01:45,650 --> 01:01:43,799
the fear response itself is part of the

1458
01:01:48,109 --> 01:01:45,660
in the subjective fear is part of the

1459
01:01:50,930 --> 01:01:48,119
emotional memory so if you suppress that

1460
01:01:54,410 --> 01:01:50,940
I also think that it doesn't work

1461
01:01:57,349 --> 01:01:54,420
because this information feedbacks and

1462
01:01:59,630 --> 01:01:57,359
is part of the reactivation of the of

1463
01:02:02,150 --> 01:01:59,640
the fear memory so for that reason I

1464
01:02:05,270 --> 01:02:02,160
also would not give it before and would

1465
01:02:08,270 --> 01:02:05,280
not suppress the fair response in people

1466
01:02:10,069 --> 01:02:08,280
with fears and phobias

1467
01:02:11,390 --> 01:02:10,079
you said that you can also give beta

1468
01:02:12,950 --> 01:02:11,400
blockers to people in the morning but

1469
01:02:14,569 --> 01:02:12,960
beta blockers have a half-life of about

1470
01:02:15,950 --> 01:02:14,579
five hours so that means 12 hours from

1471
01:02:18,589 --> 01:02:15,960
now that's almost gone from your system

1472
01:02:20,089 --> 01:02:18,599
why is it that then the memory rewriting

1473
01:02:21,829 --> 01:02:20,099
that happens at night time when you

1474
01:02:23,390 --> 01:02:21,839
sleep is affected by the beta blockers

1475
01:02:26,089 --> 01:02:23,400
earlier why does the beta blocker have

1476
01:02:27,589 --> 01:02:26,099
an effect if it's gone by the time that

1477
01:02:29,660 --> 01:02:27,599
you're rewriting your memories when

1478
01:02:30,650 --> 01:02:29,670
you're sleeping

1479
01:02:31,490 --> 01:02:30,660
[Music]

1480
01:02:33,650 --> 01:02:31,500
um

1481
01:02:34,370 --> 01:02:33,660
yeah because

1482
01:02:36,589 --> 01:02:34,380
um

1483
01:02:39,230 --> 01:02:36,599
the effect of the beta blockers is it's

1484
01:02:42,530 --> 01:02:39,240
not that it's sort of

1485
01:02:44,270 --> 01:02:42,540
I mean beta blockers we also have been

1486
01:02:46,490 --> 01:02:44,280
um it blocks a beta genetic receptors

1487
01:02:49,309 --> 01:02:46,500
there in the brain but also in the heart

1488
01:02:50,569 --> 01:02:49,319
so if you take a beta blocker in a

1489
01:02:53,809 --> 01:02:50,579
situation where you're normally

1490
01:02:56,270 --> 01:02:53,819
stressful you you feel that because

1491
01:02:58,069 --> 01:02:56,280
peripherally you don't have the bodily

1492
01:03:01,309 --> 01:02:58,079
responses that you normally would have

1493
01:03:05,210 --> 01:03:03,170
um but

1494
01:03:07,730 --> 01:03:05,220
um by the way we tested also another

1495
01:03:09,829 --> 01:03:07,740
beta blocker nadalol which has the same

1496
01:03:11,390 --> 01:03:09,839
bodily effect but does not pass the

1497
01:03:13,430 --> 01:03:11,400
blood brain barrier and there doesn't

1498
01:03:15,710 --> 01:03:13,440
work so it's really the central effect

1499
01:03:17,450 --> 01:03:15,720
in the brain that explains the fear

1500
01:03:19,130 --> 01:03:17,460
reduction

1501
01:03:22,870 --> 01:03:19,140
um

1502
01:03:25,849 --> 01:03:22,880
so the beta blocker does not work by

1503
01:03:28,849 --> 01:03:25,859
suppressing the peripheral the bodily

1504
01:03:31,329 --> 01:03:28,859
fear response it works because in a

1505
01:03:33,589 --> 01:03:31,339
specific time window it's it's

1506
01:03:36,589 --> 01:03:33,599
blocks the beta a genetic receptors

1507
01:03:39,349 --> 01:03:36,599
receptors and therefore the adrenaline

1508
01:03:41,870 --> 01:03:39,359
as a as a neurotransmitter in a brain

1509
01:03:46,069 --> 01:03:41,880
cannot signal

1510
01:03:49,010 --> 01:03:46,079
um other cells that are necessary to uh

1511
01:03:51,530 --> 01:03:49,020
synthesize the proteins which are

1512
01:03:54,170 --> 01:03:51,540
normally used for the reshaving of the

1513
01:04:00,410 --> 01:03:58,069
okay I see so Horizon and even DOTA

1514
01:04:02,510 --> 01:04:00,420
protein synthesis may take place later

1515
01:04:04,849 --> 01:04:02,520
it does not mean that all these

1516
01:04:06,530 --> 01:04:04,859
neurobiological processes take place at

1517
01:04:09,049 --> 01:04:06,540
the same time they have

1518
01:04:10,970 --> 01:04:09,059
in that sense probably their own time

1519
01:04:13,910 --> 01:04:10,980
window

1520
01:04:15,770 --> 01:04:13,920
I see so I'm pretty much wrapped with my

1521
01:04:17,809 --> 01:04:15,780
questions as far as repeater do you have

1522
01:04:20,450 --> 01:04:17,819
any follow-ups

1523
01:04:22,069 --> 01:04:20,460
um just maybe if you could as my final

1524
01:04:23,630 --> 01:04:22,079
question if you could briefly maybe talk

1525
01:04:25,430 --> 01:04:23,640
about the future challenges and

1526
01:04:27,890 --> 01:04:25,440
limitations in determining the exact

1527
01:04:29,930 --> 01:04:27,900
role and impact of propranol if you want

1528
01:04:31,549 --> 01:04:29,940
to summarize that

1529
01:04:33,289 --> 01:04:31,559
um in terms with regards to fear

1530
01:04:37,069 --> 01:04:33,299
Extinction that would be great but other

1531
01:04:43,849 --> 01:04:40,970
yeah we um we we are

1532
01:04:46,010 --> 01:04:43,859
currently working on so what is

1533
01:04:47,210 --> 01:04:46,020
important is that there is no I think I

1534
01:04:50,210 --> 01:04:47,220
haven't

1535
01:04:55,569 --> 01:04:50,220
said that so what makes it so difficult

1536
01:05:00,650 --> 01:04:58,490
exposure or in the laboratory memory

1537
01:05:02,930 --> 01:05:00,660
reactivation procedure that always

1538
01:05:04,609 --> 01:05:02,940
triggers the process of memory

1539
01:05:06,170 --> 01:05:04,619
reconsolidation

1540
01:05:09,530 --> 01:05:06,180
so whether

1541
01:05:12,829 --> 01:05:09,540
a brief exposure destabilizes the memory

1542
01:05:15,829 --> 01:05:12,839
depends both on the learning history so

1543
01:05:17,470 --> 01:05:15,839
on the memory representation itself and

1544
01:05:19,370 --> 01:05:17,480
on the

1545
01:05:21,770 --> 01:05:19,380
retrieval

1546
01:05:23,690 --> 01:05:21,780
or on the exposure so this is the

1547
01:05:26,450 --> 01:05:23,700
interaction between these two and that

1548
01:05:30,069 --> 01:05:26,460
this makes it quite a challenge it means

1549
01:05:31,970 --> 01:05:30,079
that for instance a stronger memory

1550
01:05:35,210 --> 01:05:31,980
requires

1551
01:05:36,770 --> 01:05:35,220
sometimes a longer exposure than a

1552
01:05:41,270 --> 01:05:36,780
weaker memory

1553
01:05:44,390 --> 01:05:42,349
um

1554
01:05:46,250 --> 01:05:44,400
but yeah I mean the memory is a

1555
01:05:48,170 --> 01:05:46,260
theoretical construct so we can only

1556
01:05:50,569 --> 01:05:48,180
observe the behavior and we cannot say

1557
01:05:52,430 --> 01:05:50,579
on basis of the behavior this is a

1558
01:05:55,490 --> 01:05:52,440
strong memory and this is a weak memory

1559
01:05:58,630 --> 01:05:55,500
and this is for this strong memory you

1560
01:06:01,849 --> 01:05:58,640
need a one minute exposure and for this

1561
01:06:04,130 --> 01:06:01,859
memory is three minutes so so

1562
01:06:05,930 --> 01:06:04,140
so we are actually because of this

1563
01:06:08,510 --> 01:06:05,940
interaction and in the lab we can really

1564
01:06:10,549 --> 01:06:08,520
control that and we did so so we changed

1565
01:06:12,049 --> 01:06:10,559
we can really play around with the

1566
01:06:14,990 --> 01:06:12,059
learning history in the lab with the

1567
01:06:18,230 --> 01:06:15,000
fair conditioning and then and then see

1568
01:06:21,530 --> 01:06:18,240
okay we can control if if we then expose

1569
01:06:24,109 --> 01:06:21,540
them to one or two trials it's it's it

1570
01:06:25,490 --> 01:06:24,119
works and then to a bit more then it

1571
01:06:28,430 --> 01:06:25,500
doesn't work anymore and we understand

1572
01:06:30,770 --> 01:06:28,440
why in clinical practice when we work

1573
01:06:32,450 --> 01:06:30,780
with people with a phobia we have we do

1574
01:06:33,670 --> 01:06:32,460
nothing about the learning history this

1575
01:06:36,589 --> 01:06:33,680
very often there are many many

1576
01:06:39,470 --> 01:06:36,599
experiences or it can be very implicit

1577
01:06:41,589 --> 01:06:39,480
learning or indirect we don't know so we

1578
01:06:44,210 --> 01:06:41,599
have to guess what is actually necessary

1579
01:06:47,390 --> 01:06:44,220
to destabilize the memory and this is

1580
01:06:47,990 --> 01:06:47,400
what we yeah we try to

1581
01:06:50,510 --> 01:06:48,000
um

1582
01:06:52,190 --> 01:06:50,520
to do in in our current research to

1583
01:06:55,430 --> 01:06:52,200
understand it better so that we can

1584
01:06:58,670 --> 01:06:55,440
better control when what's a boundary

1585
01:07:01,010 --> 01:06:58,680
and necessary conditions are when we

1586
01:07:03,230 --> 01:07:01,020
translate our findings to

1587
01:07:05,630 --> 01:07:03,240
um to clinical practice

1588
01:07:08,089 --> 01:07:05,640
doctor speaking of your current research

1589
01:07:11,329 --> 01:07:08,099
where can our audience find out more

1590
01:07:13,190 --> 01:07:11,339
about you and are there ways that they

1591
01:07:16,309 --> 01:07:13,200
can support you and your work

1592
01:07:17,329 --> 01:07:16,319
and that I believe will be our final

1593
01:07:20,930 --> 01:07:17,339
question

1594
01:07:22,849 --> 01:07:20,940
yeah well I can also send my Links of

1595
01:07:25,849 --> 01:07:22,859
course to the UVA University of

1596
01:07:26,070 --> 01:07:25,859
Amsterdam uh and also the link to the

1597
01:07:28,370 --> 01:07:26,080
clinic

1598
01:07:30,829 --> 01:07:28,380
[Music]

1599
01:07:34,370 --> 01:07:30,839
thank you very much

1600
01:07:36,529 --> 01:07:34,380
thank you so much appreciate it

1601
01:07:38,210 --> 01:07:36,539
the podcast is now concluded thank you

1602
01:07:40,130 --> 01:07:38,220
for watching if you haven't subscribed

1603
01:07:42,109 --> 01:07:40,140
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1604
01:07:44,930 --> 01:07:42,119
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1605
01:07:46,970 --> 01:07:44,940
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1606
01:07:48,770 --> 01:07:46,980
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Distribution on YouTube as well if you'd

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