So what I'll talk to you today about is really the neuroscience that I've been doing over the 20 years with many great collaborators.
And it's really a story that that sort of takes its beginning a long time ago.
But before we get into the sort of the history of it, I thought I'd just share it,
share video with you that sort of encapsulates that, I think what is both pleasurable but also deeply meaningful.
Hi, girls. It's August six, is that right?
Yes, August six, 2012 daddy is going to play a song when he's ready. You girls ready?
So why are they so cute? Why is it that, you know, they're moving in time together?
It sort of points to many of the things that I think we find pleasurable. But it I think foremost also points to the sociality
the sort of the idea that a lot of the things we find pleasurable is really being with other people.
And, of course, is the one thing that pandemic's has more or less deprived us.
But let's just let's just think about what is going on in our brains as we go through this.
So today I'm going to talk first about emotion, because that's really where everything starts, I think.
Talk about how we could reverse engineer the human brain.
Talk about how it is that within those emotions, we have pleasure and pleasure cycles, which are, of course, largely built for survival.
I'll talk about how one can look at that on a computer,
built computational models and actually get a handle on how it is that which
switches through these different parts of the cycle and even brain states.
And think about how that might relate to consciousness. Think about how that, in fact, might relate to human flourishing.
So let's get started with that. So many, many years ago, I came to Oxford to do my doctorate on emotion and I wrote this speeches,
as you can see here, called the functional neuroanatomy of Emotion.
And I think it was because I came to realise that really if one wanted to understand how the human brain worked.
One really has to understand how it is that we solve really difficult questions,
really difficult problems in the world and how we use emotions to guide our behaviour.
I've sort of stayed in that field some years ago. I wrote a textbook on the on the matter.
But one of the things I came to realise is, I assure you and this talk is that emotion is this sort of multifaceted molecule.
And yet it consists of these atoms. And those are really the pleasures and the pains.
And those are the ones that one could try to understand in order to stand what it is that is going on.
When we have emotions and when we act in the world, what our emotions.
Yeah. Just a random selection of different people having emotions.
And you immediately recognise that these are emotions and that you can probably recognise what the emotions are as well.
The one thing, of course, which is important about emotions is that we have them on different timescales.
We have the immediate expressions that I just showed you, which are usually having autonomic changes at the same time.
One gets nervous. One starts to sweat all of those kind of things.
And then we can report on those over minutes and hours, which then turned into moods, perhaps even disorders and the certain personality traits.
So there's a timescale to it that can last essentially a lifetime.
But how does one define them?
As always, one can go back to the Greeks and one can read what Plato wrote, sort of talking in, say, having Socrates say pleasure.
So emotions are the pleasures and the pain and pains of the soul. Aristotle was slightly more sort of elaborate.
He said the emotions are all those feelings that so change men as to affect the
judgements and that are also attended by pain and pleasure pleasures already. Then Head had the idea that pain and pleasure must be important.
Of course, what then happened was that, you know, the centuries passed, the millennials went over us,
and people like Darvin decided that he could perhaps think about how this might work in other animals.
And he said that the emotions are really expressive behaviours that communicate
information from one animal to another about what is likely to happen in emotions,
therefore affect the chances of survival of the individual demonstrating the behaviour.
So there's a key key word here, namely the survival.
And this, of course, is one of the things that emotion and specifically pleasure and pleasure cycles are good for.
But having said that, of course, along came cognitive neuroscience and Lisa Feldman.
Barrett has been a very vocal proponent of trying to really sort of parcel out what is going on.
And she she holds that emotions are constructed, events that arise from this simultaneous combination of three or more basic psychological primitives,
core effort, categorisation and executive attention.
Now, the key thing here is that the core effect is really what I'm talking about when I'm talking about pleasure and pain.
It's also clear, as I already alluded to, that when these systems are not no longer working particularly well, we get the burden of mental disease.
And as you know, this is a quite a large burden, of course,
not getting better by the pandemic where we're not able to actually enjoy the things we normally enjoy.
Now. When people then started thinking about what might be going on in the brain, which of course is what my talk is about today.
They happened upon the structures, which are sort of in the middle of the brain,
on the midline in structures that are really what we call the limbic brain, the limbic.
Really just being meaning war. And there was a number of theories out there mclaine help that there was something about the primitive brain,
which, of course, doesn't really hold up. But that was his idea. But Page was really the first one in 1949 to highlight this.
And since then, there's been great strides making Jonah Do has made a career out of telling us what the amygdala studying what the immigrant is doing.
And he's done some remarkable studies in rats showing that the amygdala is very important for fear conditioning.
In fact, he was so successful that for years people thought that the chemical really was deficit it.
Now we know that that is not true. And we also know that the amygdala probably has been superseded by the prefrontal cortex.
And in humans, after all, it's been about a hundred million years since we shared a common ancestor with with the rodents.
And in fact, Antonieta Mashal wrote his seminal book called The Cats Era from 1994, where he was claiming,
based amongst other things, and was his patient, but also on this particular patient, we were not his patient.
Both was Phineas Gauge, who was a railway engineer who basically had the job of making controlled explosions.
And one day he forgot to put the sand in and this tampering rod went straight through his prefrontal cortex and amazingly, he survived.
And they found the tampering, what, about hundred and fifty metres from there? And it can now be found in Harbord.
But the key thing is what he changed. NIRS was no longer Phineas Gauge.
We don't know a lot about this, but the measure was right to say that the ventromedial prefrontal cortex,
so the orbital frontal cortex reaches over the eyeballs and the middle part here does seem to play a huge part in having emotions, reasons and so on.
But what he KOMY forgets to say is that this is not a new idea.
James Lang, of course, you point could say that that really is setting the scene.
And one Anata, this amazing neurologist, wrote a fantastic paper from Seventy-one called The Problem The Frontal Lobe and a reinterpretation,
which is really about linking the body with the brain.
And so along came the revolution of neuro imaging, which is, of course, one of the things that I've been part of.
And with that revolution, of course, also came the new phrenology of new imaging.
So here's just a meta analysis from 2002 where they looked at all the studies and they
tried to classify the different different emotions and see where you get blocks.
And as you can see, there are blocks all over the brain. What does that mean?
Does that mean that one probably shouldn't think about localising it?
Is it so that you can't have it one to one mapping where you see Amygdaloids fear orbitofrontal cortex or something else?
Or should we really be starting to think about networks? Should we really be starting to think about how it is that we have these overlapping
networks and really look at the complexity and the dynamics of this over these timescales?
I've been talking about. I certainly think that is the way it should happen.
And so there I was as I started my doctorate back in 98.
Coming from computer science and wanting to try to understand how the human brain worked.
I came across this beautiful data that suggested that really we are prediction machines.
Here's an image of essentially black and white, and most of you won't be able to recognise it.
And yet the moment I've shown you my two daughters playing in the in the sun, you can't help but see this because now you'd have a template.
Now you have something that you can predict from. And this is true in the visual domain, but it's also equally true in the auditory domain.
Here is what happens when you have a child with a cochlear implant, which is basically a way of making that child being able to hear.
And the way that happens is basically by downsampling the signal.
So give me let me give you an example of something that is being said and let's see whether that you can try to understand what is being said.
It's very difficult for most of you, we will sound like complete noise, and yet if I play you the roar signal.
So what we hear. We don't have a cochlear implant. It's not downsampled. We get this.
The wife helped her husband. Now listen to the downsampled version again.
And you can immediately hear exactly what is going on.
So in other words, your brain. Now it has a template is able to predict and to work out what it is.
What is this signalling that noise? And so, in many ways, as a computer scientist, I realised that really evolution has been survival machines.
At the end of the day, what is important is that we survive not just this individual, but also as a species.
And really what happens is that we've built a system that has hierarchical prediction.
Other people have had this idea. Culturist and of course. Keep it. Bownds and Clark is another one.
And really, what this basis. This idea that we have predictions and that we have these emotions that helps
guide those predictions is that we can solve what is known as NPR problems,
nonpoor and human problems, problems that are so hard that most computers can't fix them.
And so it means that in order to really reverse engineer the brain, we need to understand this system and we need to understand it over time.
We need to understand the long lasting kind of cycles that I've talked about, but also the very short ones.
So I didn't have my coffee just before now. And of course, I'm thinking about coffee.
So there's a pleasure cycle. We'll see in a moment.
But also, if we understood how that worked, we also much more likely to be able to understand what happens when there are imbalances,
anhedonia, the lack of pleasure, apathy, the lack of wanting things are fundamentally changed in most new psychiatric disorders.
And really a bit of understanding might be able to give us a better understanding of how we could intervene.
And so I think that's all well and good, but of course, the key issue, how is the brain organised to start with?
And again, people have been thinking about this for a long time. One of my favourite examples is the Massive Metronomes, his 1998 paper in Brain,
where he basically shows that there's a hierarchy of things that the primary visual cortex V1 sends
signal on to higher and higher levels and they're up and downstream connexions between these things.
And the key thing is that they're organised so that as you get higher and higher up, you get more and more integrative.
And here he's just showing what happens. The same for the auditory system and ensuring showing what happens when you then integrate that.
When you integrate that model. And in fact, Bernard Barres had a wonderful idea that he said, really,
what is going on here is that you have all of this information coming into a global
workspace and basically then that information is broadcast to the rest of the world.
Now we'll get back to the global workspace, because I think that's a key idea here.
Dominant shellers, of course, immediately said, you know, in their theories,
that is really about how it is that we bring all of these things together in a in a
in a in a system that is able to actually do these things with scheduling and so on.
So just as an aside, because this is also, I think, what is important when one does this kind of work,
when we did the first experiments of just looking at what happens when you just get the different kind of five sensors in, do you bring the notes?
Of course, there are more than five sensors, but just the classical ones, the auditory, the visual, this multisensory, the smell and the taste.
What happens then is we were able to make sculptures of those. So just basically the low was part of the hierarchy.
And here's just a close up, one of those with my good friend, Andy Catrell.
So in other words, we basically were able to show what are the parts that are involved in this?
The outer ring. But the key thing, of course, if one wants to understand the system in reverse,
engineers understand what happens in the middle in this global workspace and shampooer.
As you understand, the hand came up with an influential implementation of Barzeh ideas,
namely to say that really when we doing things, we have things coming in perceptual systems.
We have the past. We have the value system, which is the emotional system, and then we have an attentional system.
And that basically predicates and allows us to basically look at the future.
And they also did a number of beautiful experiments that allowed us them to say that really one
shows things that subliminal strength is not able to get in and therefore is not conscious of it.
And you can even see things that you're not conscious of, like if there was a gorilla walking through the room and I'm focussed on talking to you.
I may not be able to see it. I could have attentional blindness to that.
So that's kind of interesting. But in order to get to there, we need to first think about the reward system and the story of pleasure cycles.
I think it's an exciting one. As I said, you know, right now I'm on wanting coffee.
I'm thinking about coughing. I'm thinking about how I could potentially run out and come back and then finally have a bit of pleasure food.
Of course, it happens in the beginning for the pleasures of a bit later. And then there will be a phase transition.
Once I've had that on me to join then and I'm able to do something else.
Now, if I was addicted to coffee, which of course I'm not, I would spend all my time here and probably wouldn't spend very much time here or here.
So in other words, you could see how it is if you could identify what is one of the circuits that are doing this that could basically
see whether one could find out what is going on and how potentially to help you not get stuck in those attractors.
So in other words,
you can have prediction and meta stable status cycles and networks you need is in order to have the resource allocation for survival.
But we also limited we have a limited bandwidth in the inner circle, as it were.
But key to this is that these rewards are motivational magnets, just like those two babies that you saw in the beginning.
You can't help but actually look at them even if you haven't had children yet.
And really, the pleasure psychosis is essential for the necessary decision making.
And so to think about that together with Christine,
aren't we sort of started thinking about how it is that you have in this state where I'm sitting here thinking about the coffee,
you have all these experience, all these things coming in, perhaps even the smell of coffee,
and you have to make predictions about what you need to do in order to get to that goal.
And so in a very kind of a very kind of simple way,
one could start to think about how it is that you have this search tree of different possibilities
and really the reward values and your past experience allows you to discard suboptimal options.
And this just doesn't happen now. It happens throughout the day.
Only three coffees. But, you know, it could be many more. And, of course, there could be many different kind of cycles.
There could be things that I'm doing as well. And as long as I'm engaged in that cycle.
That, of course, could and will very highly influence the well-being that I have over the lifespan.
So in my work, I've looked at probably all of the pleasures that are here.
I'm just showing you for food from the top. And what you and social on the right drugs,
methamphetamine giving to dropping is oxygen undergraduates and gambling again, gambling that if octomom graduates.
And when we use these scanners, what we found is that the orbital frontal cortex, the part that you saw was the MASHU, but that I am also.
That clearly is coming up here. The parts of the brain that adjust over the orbits, the eyeballs is really the engaged version.
And, of course, with subcortical regions, as you can see here, when it comes to the drugs, but also put the other one of those not showing.
But I think key here is that this one system for all of these things,
it seems to focus on one system and that one system includes but is not limited to the orbital frontal cortex.
And much of my career has really been spent trying to try to find out what the orbital frontal cortex,
where things are when things happen and what is going on.
And one of the few pleasures that I couldn't do myself, I had to bring in that doctor,
collaborator Janika Grigoriadis, who sort of Masters and Johnson's rolled into one.
And he did this beautiful study where he looked at what happens when when women fake orgasms and when they have orgasms.
And what he found was that when they have real orgasm, as you can see,
you get a very large engagement of the orbiter for the cortex compared to when you are just imitating.
Which is not surprising, given that the pleasure circuit, of course, has to engage the very same one that you used for so many, I think.
Of course, it's a bit frivolous to talk about orgasms here on a on a Thursday afternoon.
But really, I think what is exciting here is really the kind of orchestration of of of activity,
how it is that one goes from desire and how different regions are active.
When you aroused, when you get to the plateau phase and even when you get to the orgasm phase.
So this kind of orchestration,
this kind of choreography of different brain regions changing is really what we are trying to understand when we understanding pleasure,
not just on a single level, but on a whole brain level. And of course, is very similar if one was to look at music.
So in beautiful work by and Lord and Robert Santora from McGill,
they were able to show that when you have the kind of music that where your hair stands on end, you get a very similar kind of network engaged.
Now, they weren't able to say anything about the win because this was a pit study,
but they were very much able to show that it's the same network that is engaged when it comes to these kind of pleasures.
So that's kind of exciting is one of the things that we do in the centre in all
who's at the music in the brain centre where we have all kinds of fancy machines,
but also extraordinarily gifted musicians, including our director Peter Russo, who's here playing the bass.
And as you can see with Graham, and we will continue to grow because we've been extended for another five years.
So, again, if music is your pleasure, you should definitely talk to me afterwards.
But before we sort of look at the commonality of things,
let's maybe just focus on the social pleasures and let me focus on perhaps what is the most simple.
Even those social pleasures are never simple, but the most simple of all of the pleasures, namely that like.
I mean, look at these babies recession. It just goes on and on.
So why are they so cute? Why do they look so cute and why is it that we hear them this cute?
Well, it's very clear that we must be motivated to do something about them because,
of course, the species survival and the survival of the species depends on it.
They're vulnerable. They come out too early. So we need to take care of them.
And if there's something wrong with the parent, if postnatal depression, that causes a problem, that potentially could need some help.
But also, if there's something wrong, the baby like a cleft lips or the template doesn't fit the kind of expectations we have of what babies are.
So I got very excited by this back in the early 2000s and we started using this kind of scanner,
which is an image scanner, what some people call an advanced hairdryer.
But what is cool about it is that it tells you something about the when it tells
you something about how things happen over milliseconds because unlike bold.
So that is if I am right.
It tells you basically how these different things are moving about on a millisecond to whether thousands of a second around the brain.
And I was interested to look at the current Rentz idea of the of the Kenshin schema.
The idea that there's something special about babies. And so we took happy babies.
No neutral babies and sad babies and matched them to some adults.
And then we started looking at what happened in the brain.
And at that time, everybody thought that it would just get activity in the fusiform face area,
which is the part of the brain that Oliver Sacks described when he talked about the man who mistook his wife for a hat.
Because if that part of the brain is no longer functioning, you're unable to recognise faces.
Now, you get that, as you can see here, after about one hundred and thirty milliseconds, both for the adults and for the babies,
but only for the babies, do you get this activity in the emotional part of the brain very quickly.
And then he sort of dies out. So in other words, it looks as if.
What is very special about babies is that they at the same time as you recognise them as being babies,
you get the signal that says I must be taking care of that baby.
And we were able in later work again with Christine Parsons and Katie Young and with the restart to show and with Ellen Stein, of course,
to show that there is something very special about if there's something wrong with the template, if there's just a tiny change in the mouth.
We notice immediately. And interestingly, when you look at the brains of, again, non parents having a look at this,
what you find is that there's a much diminished response in the orbital frontal cortex and also, by the way, in the fusiform face area.
So in other words, this prediction goes awry. And this, of course, could be a problem.
And unless one does something about it, one could then later have problem with the bonding process.
But, of course, now that we know, we can start to think about how we could intervene in that, in effect, in a set of studies that we are conducting,
we have shown that at least the way that nurses and surgeons report on these babies is that they say,
can you see how cute their baby is because they've changed their template? And how do we change the template so that we can engage in a natural way?
So I think that's exciting.
But it's also exciting to see that, again, if we look at the auditory domain here, just looking at comparing infant and adult crying,
only the infant crying gets you activity in the orbital frontal cortex again,
telling us that this early, early response that is guiding our things is really found here.
And it's found in people who are not parents.
And so, in fact, for the last five years in another project I've been investigating, funded by the U.S., see what happens as we become parents.
What happens if we scan people before we want to have children, after we have the child and then a year later and both the mother and the father?
So, again, we haven't published on this yet, but it does look as if there are very significant changes in the brain when you become a parent.
And all of us who are parents will know that this is true for many different ways.
But there are clearly changes in your brain. Clearly changes in your hedonic system.
So together with Roger Chris, I we sort of investigated all of this and we basically wrote this paper where we state
that by revisiting this conundrum in philosophy about high and low pressure pleasures.
And we concluded based on this kind of research and the research of all the people in the field,
that really it seems to be like in Lord of the Rings is one to the mall.
There is a network that is engaged that is similar no matter what kind of pleasure it is.
There is, of course, an interesting question, and that is why does it feel different?
But it's the same system and that system here we show in the rat because one can study pleasure in the Raptors.
Can Berridge from University of Michigan has shown beautifully by giving rats a little
bit of sugar water and basically measuring how many times they lift their lips.
Which, of course, you can also do babies who can report on it. But when you do that, you find the circuitry and you see the orbitofrontal cortex.
But you also see other regions like the nucleus accumbens and ventral part of them that are part of this network.
This kind of workspace that basically allows us to feel pleasure.
And if something happens to them and of course, in rats, they've tried that.
If you take out the ventral palette, them the rat is never able to show that pleasure reaction again.
And here we've tried to extrapolate it in the human brain.
And again, what you can see is that a lot of these regions are very deep in the brain and fairly well protected,
which, of course, is well, because otherwise it'd be very difficult to survive.
So in other words, what we're really talking about here is going back to Aristotle's radical idea that there's
a difference between who donia this idea of heater's sweet taste of honey as pleasure,
which is essential for food, for survival, with a beautiful food, for the individual being six,
or actually being able to propagate the species and of course, the social aspects.
And then you turn Monia, namely, the life will lift embedded in meaningful values together with a sense and engagement.
It's subtle and complex. And what we can say, though, is that the lack of of well-being and mental health can be devastating.
But what we also know is that it's very difficult to measure. It's very difficult to find somebody.
And like a rare butterfly. How do you find somebody who is actually flourishing in a brain scanner?
I think it is possible to do that.
And we'll talk a little bit about how that might be possible through music, through social, through psychedelics and through meditation.
But in order to be able to do that, one needs one more ingredients.
And over the last, again, almost 20 years, I worked with this wonderful man, Gustavo Decco,
from Barcelona to try to see whether we can actually simulate the human brain on a computer.
And as you can see from this neurone paper, we have great expectations that by doing so,
we are able to take the data off normal and off people with disease and try to see whether we can characterise
that on a computer model and then treat that computer model just like we would treat an experimental animal.
But unlike with an experimental animal,
we can basically we can sobek this model to extensive research over a month and even years to find out how did we rebalance that.
In order to do that, though? I have to bore you with some really exciting science, which is what is called complex networks dynamics.
And at the top, you see a sort of a video of a larval superfish and you see from time to time that you get these kind of bursts of activity.
It means that the brain is critical, as has been shown.
And it means that reading, in order to understand that we need some of the tools that have been been basically been built in physics and mathematics.
And one of the first tools is, B, to take Thomas Aquinas equip, sort of talking in Aristotelian manners.
He said quite quit receiver to a modem recipient is receive better.
The content is shaped by the container.
So what we do is we take the wiring of the brain, the truck, top graphy, as is known, that we can pull out of the living brain.
We pass on the brain to make the problem a little bit less.
Rather than doing an order billions of neurones, we're doing it on large brain areas that seems to be doing the same thing.
And then we try to build a model that can fit the data that we get,
either from it from Orion or from G, from any thing really as long as its whole brain.
Because, again, it's important that we're not just modelling a small part of the brain, but that we are modelling the whole dynamics of this.
And just to give you a flavour and it can only be a flavour. But of course, for those who are interested, we should talk much more about this.
But really, we need a term in our models that describes the intrinsic dynamics of the market.
We need something that describes the KOPLIK. And as you can see here, the yellow is not directly connected to the green.
And so really needs to go through the red. And of course, that can happen once you have a dynamic model.
He has some equations that worry too much about them.
But just to show that there are many different ways that one can describe these neural masses and they have various pros and cons, all of them.
But the one that we like most is really this one. Hofbauer Vacation Modern, which is is due at Landauer model,
which is a beautiful way of actually capturing a lot of the information that is being encoded in the human brain.
And in order to do that, we can then perform interpretive studies of the brain, not just as here and beautiful stories of muscle mass in any.
He is trying to show what happens when you give to your miss on the outside or when you're
using deep brain stimulation is not sure you in a moment to stimulate deep in the brain.
By doing this, we can actually find out what are the mechanisms that are causing those changes.
So in other words, we can take the healthy brain. Look at the Healtheon Working Network.
We can take the Zis brain and we can try to stimulate and see whether we can form what we call a
static recovery of turning that disease brain or that different brain state into a healthy one.
So in order to do that, we got quite excited. And this is work with anchors Stefano.
Was a our postdoc. There was a Puchi student with me who was able to show that what happens when you
fall asleep and basically one can train a network to find out what are the stakes.
That happens when you fall asleep. And classically in in in medicine, it's been said that there's a awake.
Then there's in one. Then there's in two. And then they're slowly asleep or deep sleep.
But what you can see that this unguided algorithm was showing us is that there are many more states.
And in fact, Angus was able to show that as you fall deeper and deeper into sleep,
you have a change in each of these represent the brain network and you can see how much time is being spent when you're awake.
So a lot of in state 10, which, of course, is a set of brain regions.
And I'm not showing you here, but that you can find in the paper that basically is the interface transitioning and finally getting to in three.
Now, thinking about this in a more reductive manner,
could one find a way of stimulating the brain to the you can go from deep sleep all the way up here to force this transition that I showed
you earlier by having a computer model of the deep sleep and of the awake and see whether you can force it one way or the other way.
And so we were able to do this recently in a paper that came out in PNAS where we basically were able to model the data and find out
by trial and error an exhaustive search where to stimulate in order to force the model from one way to another is just some data.
There's no you with here's what the data looks like from the empirical data.
This is what the model of. For when you're awake, this is what happens when you are deep sleep and this is what the model looks like.
And this is basically the regions that are involved in it. Now, within stimulated each one of them.
And as you can see, as you stimulate this model, you find that the money comes from sleep to awake.
There are lots of places that you can stimulate in order to wake the brain up by synchronising if you noice it.
However, there is no way that you can do it, on the other hand, is much, much harder,
as you can see on the scale here, too weak to take the awake brain and fall asleep.
And this, of course, fits really nicely with what we feel as well. This is like a toy example.
This is not something that is clinically relevant yet, but it shows in principle that we can do these things.
And I think that's very exciting because it means that we can now take these networks from people with
disease and think about how it is that we could use these models to force them into a normal state.
But rather than doing it just brute force, we could go back to this idea of the hierarchy.
And we worked very, very hard, Gustavo and I, to basically.
Work out how we could find out what the Herrity of the brain is,
and we developed a method called Normalised Ulbrich Transfer Entropy that allows us to take any time series
and basically find out whether it's forcing another timesharing or is being caused by another typesetters.
And if you do that, you can basically establish from this matrix of all these different brain regions,
you can establish the hierarchy and you can establish the regions in the brain that get a lot of information
in and basically keep that information to themselves until they broadcast it to the rest of the brain.
And you can do that not just when you're resting, but when you're doing many different tasks.
And in this case, in a thousand people, we had seven tasks. So we look at what is common to all of them.
And then although I will show you here, you can be did in the paper,
we create a model where like a model, hi, Hydra, Multiheaded, Hydra, we cut out these regions.
And when we do that, we are able to show that if we cut out the ones that we've identified that are now in the global workspace,
the whole system breaks down. If we only take out a few ones of them, the system is still able to recover, which is good.
But of course, it also means we can then think about how can we then make this system rebalanced?
So when you do that, you find that again, these are the regions that are in the visual cortex, so much entry cortex.
Those are the ones that just put a lot of information forward.
So they're the lowest part of the hierarchy by the integrated part.
And this is the brain sort of seen from above.
Just like one would see a map are basically the regions that are on the midline, the ones that are to do with emotions and with attention and so on.
And I'm just showing you this other slide just to see that if one changes the population, you get very similar results.
But the money shot, if you like, is this what you find when you look at all these seven task and the resting is that you get this network of regions,
these regions that are really to do with perceptual systems. They're really to do with long term memories.
Paya's like the hippocampus. They're to do with evaluative.
The amygdala is in there, the the the nucleus accumbens, the right eagerness is singular and so on.
So they are regions here that really in many ways substantiate the idea.
And the theory that that Shannon Dramane shampoo your shoe and stand Hinden and Bernard past came up with.
So for the first time ever, I think we've identified what are the regions.
And of course, if one then wants to change the state from one state to another rather than trying to stimulate everywhere,
like in the visual cortex, when we know that the visual cortex is not really something that necessarily changes anything.
We could then start with the top of the hierarchy, the parts of the brain,
the the hierarchy of elders that basically are making the decisions and making the transitions.
So I think that's potentially very interesting. Of course, it fits very nicely with the kind of work that I've done with sequences where we've
tried to work out what happens when you are giving people deep brain stimulation.
We do this on a routine basis based on people's great discovery.
They knew that if you stimulate a place like this ophthalmic nucleus in people with Parkinson's,
you can basically Cuil the tremor or as TIPO has always shown and here you see him with
somebody you might know is that if you stimulate forth somewhere where you have chronic.
Debilitating pain, namely in a phantom limb. So in a hand that is no longer there.
If one stimulates the pirika Dr. Grey at 20 hertz, you can make that pain go away completely.
Now, interestingly, and we do this on table in these patients,
when you do this and you then stimulate them and you listen to what they tell you, if you stimulate a knighthood in exactly the same place,
the pain, the pain becomes even worse than before, suggesting, as we've already guessed, that pain and pleasure really two sides of the same coin.
And if you then put them in a scanner and you turn the stimulator on and off,
what you find is that the orbital frontal cortex seems to be very much active.
When you get the pain relief or the pleasure of moving from one state to another.
And so, again, with anyone I talk to about this, she couldn't help herself or say we got a built, we got to build some sculptures of theirs.
And we made this wonderful sculpture where we were able to basically track where this point we're stimulating,
where this bifurcating point that either give you pain pleasure, where that projects in the rest of the brain.
And it's a I think, a beautiful kind of thing, a sort of a pain and pleasure made flesh.
But of course, the brain is a large place. And I just wanted to give you a sense of what can be accomplished if one is actually stimulating.
And this is for for basically to try to to do simulant stimulation.
And this is a beautiful study where they stimulate in different parts of the single.
And remember, the cingulate is just part over your of the sort of where you can see here in the midbrain if you stop your
fingers or the way sort of four or five centimetres in and you can see that there is a certain place in our.
Now just play your video where they get some very interesting results. It's like you do it.
It's. Yes.
I. Think you can do that. I think they're like I crazy.
He plays into it every single time you see Michael.
So they should be. This is awesome.
To me, that is a silly assignment.
I get against them. Yes.
I think it's an evil. And so I encourage you to go and actually have a look at this,
so it appears that they've found a place in the brain where in voluntarily the patient can't help but feel good.
So I think one of the things we we've taken discussion is just think about whether
this really are such pleasure electrodes where you are perturbing the system.
In this case,
it causes an end to your Lytic patient and you're forcing that patient to basically go to a place just like with the with the with the hand,
with the chronic pain. You're going into a good place, as it were.
But again, let's talk about what that actually might mean, both in terms of the neuroscience, but also very much in terms of the of the ethics.
So is it true then that this target state that we going for?
And remember, there was a target statement. I showed you how you live from deep sleep to awake.
Could there be a target state where you read one really is you demonic?
Everything is. It's good. So one could study that with many different ways, one could study with meditation.
And can we sort of got some beautiful meditation data and we could listen to more looking at Janna's.
This is work with Jamila and Daria and also the psychedelics in work with Robin.
Can't have Herries and various other people. Miss Johnson and music, of course.
These are states where reliably we can't seem to induce something that people describe, at least afterwards, as a very meaningful state.
And so let me just give you the example of psychedelics is the work of Sulin SSR.
Who is this wonderful researcher that I work with many years, who's come up with an alphabet,
if you like, of the sort of the harmonics, the harmonic functions of the brain?
This is a beautiful paper from 2016 that basically gives you an alphabet of which you can
then spill all the different states that one hand we call these functional harmonics.
And basically, it's a framework that allows us to take these basic come on X and then find out how
it is that in different states they spell out different kinds of frequency spectrums.
And if we then take robins in this data with music, without music, we can see that there is a change in the energy spectrum.
When we look at enlistee compared to placebo and you can see there's a very significant difference.
There's also a difference in the criticality in the power law exponents.
But there's also a difference in the way that the repertoire is being expressed.
It looks like that enlistee basically increases the repertoire.
It looks like it's in the brain suddenly is able to explore much more of that landscape that it will go through normally.
And it's true not just for enlistee, but also for psychedelics like psilocybin.
Very similar results, as you can see, for psychedelics or psilocybin, rather.
So that's kind of exciting. But of course, what is really exciting and this is work by one of my student, Chappell Vasek,
begin working on Robyn Stacey, where Robyn gave psychedelics to depressed patients.
And he was able to show that in some of these responders, they got much better.
And it is very, very early on. And then after a while, it faded.
But if you read The Lancet psychiatry, the effects are very strong. Now, he also had new imaging of it.
And what we are doing here is we are trying to see what happens when you have and you use these computational models that we have.
And you can start to think about how it is that we could look at the nonresponders and find out what it is about the brain response that
is different from the responders and see whether we could force at least the computer model to actually give us that kind of response.
So this is an ongoing and really exciting area of research. And I think it has huge potential for actually being able to really help with things like
depression and really understand the mechanisms by which the serotonergic drugs are working.
So I think this is potentially exciting and I think something we can talk about as well.
And I think really that's about as much as I wanted to say. I wanted to say also that it's not just about the brain.
It's about empathy is about other people. For those of you who don't know about it, you should go to my friend Roman Kazunori,
who is standing here with a pair of shoes and try to see how one can, in fact, doesn't really need just to have electrodes put in your brain.
But even listening to a story and walking a mile in somebody's shoes can really change you.
I think that's potentially something else.
And I think it also points to something that I'm very keen on, namely to say that this is really a multidisciplinary endeavour.
What our show is today is just some of the neuroscience, some of the selected bunch of neuroscience that I've done over the last 20 years.
But it's by no means the full story. Really, what is going on here is that one needs to look at this from many different angles.
And with this in mind,
one of the things that will be happening over the next year or so is that we are setting up a new centre centre for eudaimonia and human flourishing,
which we'll be working closely with you here, Hero Centre,
to try to see whether we can't bring these multitudes of perspectives together and try to see whether we can finally catch that butterfly,
or at least part of that beautiful, rare butterfly, which is well-being or flourishing.
And see whether we can't characterise it both in terms of what happens in the brain, how it feels and how we might be able to rebalance it.
So thank you so much. I'll leave you with this image of my my wonderful lab and some of my collaborators.
I should point out Peter Boost and Einstein, Kent Berridge and Peter Whybrow at the top,
but of course, also Gustavo Teiko, who's standing in there in the middle.
Thank you so much.