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Joseph LeDoux: Emotion, Cognition, Consciousness, Behavior & Brain Evolution | #73

Full episode transcript below. Beware of typos!

Nick Jikomes

Professor Joseph Ledoux, thank you for joining me.

Joseph LeDoux 4:46

Thank you for having me.

Nick Jikomes 4:47

Can you start off by just telling everyone who you are and what your scientific research focuses on?

Joseph LeDoux 4:52

So I'm Joseph Ledoux. I'm a professor of neuroscience at New York University. And I've worked on On problems about emotion and consciousness for 4050, or something 45 years.

Nick Jikomes 5:08

Yeah, so you've been doing this for a long time. You're also an author, among other things. Your last book, which I read through recently, it's called the deep history of ourselves before billion year story of how we got our conscious brains. And one question I'd like to start out with is, you say early on in the book that, you know, normally when we think about behavior and consciousness, we think about animals with brains, especially the biggest and most sophisticated brains. But you're right, the behavior is a feature of all organisms, not just those with nervous systems, and muscles. So what exactly is behavior in the most fundamental sense,

Joseph LeDoux 5:47

it's the behaviors, the ability to move around in the environment, to respond to the environment. And this is, you know, when we talk about approach and avoidance and a human or rat, we think of that as we're doing that, for some psychological reason, we're approaching things that are useful to us and avoiding things that are not so good for us. And if we start looking at how far back in evolution that goes, what we find is it goes all the way back to the beginning of life. The earliest cells that ever lived some 3.5 billion years ago, or however long it was, had to be able to detect and respond to danger by moving towards and away from things moving towards nutrients and away from harmful things. And this is something that every organism really needs to do in one way or another. I mean, even if you take a tree, it's got to extend its roots to places where there are nutrients and liquids, and it has to withdraw if the soil is toxic in some way. So these are just parts of what it is to be a living thing. It has nothing to do. It has nothing to do with psychology, it's just about being a living organism. Whether you're a single cell or a complex organism, you all have to all cells have to do that fundamental thing of approach nutrients and avoid danger, withdrawal from danger, they also have to be able to incorporate liquids or drink liquids in some way to balance their fluids and electrolytes. They have to thermo regulate, and they have to reproduce with their species to continue. So these are just fundamental things that are important for the survival of the organism have nothing to do with psychology. Of course, if you are psychological being like we are, and like lots of other mammals, at least another question whether I would question whether invertebrates are psychological beings without but get us into a whole controversy I don't want to go into. But you know, certainly humans and other mammals are psychological beings in the sense that we do things with intention that we have goals, and we try to approach those goals to solve our problems. But that's a whole nother level above the sort of routine neurobiological level that allows you to survive if you're an animal, or the basic biological requirements if you're not an animal, but you're still a living thing.

Nick Jikomes 8:15

And so, you know, if someone's interested in studying psychology and studying aspects of how the brain connects to the mind, why is it useful, or perhaps even necessary to understand the behavior of even the simplest single celled organisms,

Joseph LeDoux 8:30

but the importance of the single cell organisms, at least for me, and my interest in animals that are close to us, like mammals and primates, and humans, other humans, the important thing is that some behaviors are, have nothing to do with psychology. And we can get, you know, we can talk about a simple kind of classification. So you have reflexes, we're now we're talking about Alex, you have reflexes where they can detect something sharp or hot and withdraw from it. Or blink their eyes if, if something goes into it. So that's a low, very low level of behavioral responding that doesn't require any, you know, quote, psychological involvement. The next level up would be fixed action patterns, things that the ethologists made famous in the 1940s and 50s. These kinds of instinctual behaviors that most organisms have some form of that helps them survive. Again, these are automatic responses to the environment and not things that are necessarily, quote psychological. at a slightly higher level are instrumental responses that have been learned through trial and error and instrumental responses response that you learn to do because it has some benefit or consequence to it. But in most animals, instrumental responses are of the trial and error habitual type. In other words, once you learn it from the basis of the reinforcer if you've repeated it a few times enough times, it becomes a habit. And so the habit is then are expressed automatically. So again, we're talking about a behavior that you might say, well, there was some psychology involved in the learning. But that's even that is dubious, because habits are learn on the basis of reinforcement. Let me backtrack one step and go back to these these innate reflexes and fixed action patterns. Because there's a version of those that falls between or below habits, and that version is Pavlovian conditioned responses. So bacteria, protozoa, all organisms seem to be capable. Many organisms also don't want to make it to bowl, many organisms, single cell and multi cell are capable of undergoing Pavlovian conditioning. And that's where you have some stimulus that's presented. And it has some meaningful consequence to the organism, whether it's the induction of some kind of tissue damage, as with, say, let's say you have a rat, and you give it an electric shock in the presence of a tome, there's a potential there of tissue damage, which the shock sends to the brain. And that gets paired with the tone so that the tone now elicits a defensive response like behavior.

But the end, you can do this with also with with positive or repetitive stimuli of food, a stimulus paired with food will lead to approach to the stimulus. It's interesting that the aversive stimuli can produce one trial learning. But it's very hard to get one trial learning to a kind of repetitive, positive, rewarding reinforcing stimulus. And that's very interesting. And I think it's because things that are dangerous, and harmful, have to be responded to immediately you can put off the good stuff in life, you know, eating drinking sex, you don't have to have that every time there's a stimulus that's relevant. But you do have to respond to danger every time there's a stimulus that's relevant. And I think that's why the you get that dissociation there between appetitive and aversive Pavlovian conditioned responses. So reflexes undergo Pavlovian conditioning and fixed action patterns undergo Pavlovian conditioning. So when a rat freezes in the presence of a tone that's been paired with a sharp, that's an innate fixed action pattern, that the animal has the ability to do to a natural stimulus, but that can also be changed through Pavlovian conditioning. So that is a very fundamental and simple kind of learning, that adds to the, to the the range of use of these innate responses. But now we go back to habits, habits are a different thing, because with a habit, you're learning a new response. It's a response that you didn't have in your repertoire. But because the response is reinforced, it gets added to your repertoire. Now, this is a problem of trial and error learning. It's about how a reinforcer changes behavior. Now, there could be in the presence of an aversive stimulus, some, quote, fear. And in the presence of an appetitive stimulus, a positive stimulus, there could be some pleasure when the reinforcer occurs. But one of the problems we've had in psychology is the confusion of these subjective states with these basic responses that don't require there be a subjective state. It's not that we don't feel, you know, pleasure when we have a nice tasty meal or having sex or that we don't feel fear when we are in danger, because we do, obviously we do. But when we project those emotions that we obviously know and feel onto other animals, we're confusing the history of our survival behaviors, with emotions. Emotions are something that is quite different. And you may want to wait to get into that later in the discussion, but I thought I'd just bring that up. So let me just finish this hierarchy because after the habits, we have instrumental responses that are goal directed. These depend on the creation of a middle model, an internal representation of the organism in the world and that relationship. And when that comes into play, that is quite different from a habitual response. Very elegant research by Tony Dickinson and Bernard Beilein. I'm at Cambridge, they were both there at the time showed that the, the animal has to the difference between a habit and a goal directed action is that one involves the representation of information, independent of the external stimulus. And that is a special kind of quality that that some animals have. And my take on this is that birds and mammals have it. But other animals don't have it, they have habits. Now, it's interesting to ask why birds and mammals have it. And other animals don't. What's What is it about birds and mammals? Well, they're both warm blooded. And if you're warm blooded, you have to generate a lot of energy to keep that warm bloodedness going to, you know, to, you got to have the fuel to have that, that warm blooded, that's got to create heat in the body, and you have to consume food to do that fuel. And that's a very energetic kind of process, you know, it's very demanding, the organism has to be able to know when to go searching for food, where it's likely to find it, what the consequences might be of going to the spot versus that spot, is that the right time of year for that kind of foods at the right time of day for the predators and so forth. So a lot of planning that's required to maintain that body heat, birds and mammals seem to have this ability to create these internal representation, these models that allow them to plan. And that may be a sign of a sort of side effect of being warm blooded, which is a fascinating idea that I read about recently.

Nick Jikomes 16:39

So there are these different kinds of behaviors. Some of them require a nervous system, some of them do not so simple. Pavlovian conditioning is something that doesn't actually require a nervous system, because animals without neurons are capable of doing it. So if we think about the simplest nervous systems when the nervous system first of all, what are the most primitive organisms with nervous systems alive today? What are their nervous systems doing and not doing compared to more complex creatures like ourselves?

Joseph LeDoux 17:07

Well, so the the simplest, kind of the earliest animal that we know that's alive today is a sponge. Sponges don't even look like animals or so they're just gone and they don't move. So they're hardly they move a little bit, they kind of like, can make very small movements over very long periods of time, they more like a plant in a sense. But one possibility is that sponges once had a nervous system, and then gave it up because they were able to create a sessile life that allowed them to do what they needed to do to survive. Or it's also possible that they never had it. And that nervous systems first appeared in the next group of animals, which is the group that contains jellyfish, and hydro, and so forth. So these organisms have what's called a diffuse nerve net. It's just a bunch of neurons that are interconnected, it's kind of like, you know, a neural net, and a computer program is just a bunch of neurons that are connected. But all other groups of animals after these jellyfish like organisms, animals that are called mezzo zones, they are bilateral animals, they have a front of back a left a right and a top and a bottom. Whereas jellyfish just have a top and a bottom. animals that have all those different parts and the ability to move in different directions, and to be able to do things in the front and the back, have to have a more complicated kind of control. If you touch a jellyfish anywhere on its body, it produces a generalized kind of response. But if you touch an animal in a certain place, you get a response. Usually at that place, for example, you the hand withdraws, the whole body doesn't withdraw unnecessarily. So nervous systems allow very precise control of the inputs coming in. And the outputs going out of the nervous system. And a jellyfish is just all the big mush of things interconnected. So I mean, that's probably an oversimplification about the poor jellyfish. But there is a quite quite a difference between having a central nervous system that can exercise top down control over the body, as opposed to a nervous system that simply can respond to stimuli that occur. So that's the main difference between nervous system in these lower animals and nervous systems in animals that have bilateral bodies. So in a bilateral body, the brain is in the front. Why is it in the front? Well, that's if you have the front and all of the sensory organs. Most of the sensory organs are located there. It's a short distance to the brain. So all of that can be coordinated. And then you can get the signals back to the body to make the kinds of movements that are necessary. But having the brain in the front, and that being the forward direction of locomotion means that something coming at you from behind might bite off your tail. But at least you're gonna still have your brain your ability to control the body in a reasonable, you know, kind of predictive way of the environment.

Nick Jikomes 20:22

So, you write in the book, and it sort of gets that what you're just saying that the nervous system in the most fundamental sense, is a sensory motor integration device. So whether it's a jellyfish or a human or something in between, there's there's something fundamental about sensory motor integration, coordinating the inputs coming into the sense organs with the outputs being what the muscles are doing.

Joseph LeDoux 20:43

And much of our brain is devoted to this process as well, detecting stimuli and responding to them. I mean, the most basic level of the nervous system, the reflexes, but sensory motor organization, is fixed action patterns, those are often motor programs that have been instituted by evolution. So that the, there's some some stimulus in the environment that was dangerous to the ancestors of an orgasm, and that kind of stimulus information, then it's automatically programmed to elicit those kinds of responses. Above that, are these Pavlovian these learned responses, conditioned responses and habits. And then we get more into the goal directed kinds of model based behaviors. So yeah, there's, there's lots of different ways of controlling, and you have to have a central nervous system to exercise the right kind of control over the right kind of response. But most of our brain is doing that the basic kind of kind of stuff, you know, in a way that you could think of the brain, the human brain as being composed of billions of, of learning program cells, that each cell has the ability to learn. And we don't always know about that learning. But we the art, ourselves, just as we are adapting to the environment, the cells in our brain are adapting to the changes that are happening in its in their environment. So they don't know the outside world, they just know the inputs from other neurons. And that's their, their little local world. So each neuron has some inputs, and it has some outputs. And as those inputs and outputs change, those neurons change their characteristic. So throughout our brain, all those neurons are acquiring information all the time, usually, as part of, you know, more complex systems. But even the the various circuits and synapses and systems that we have, are made up of all these little cells, or cells that are connected together, or cells that are even more connected together and larger, larger schemes. But our brain is is, I think, in the most fundamental sense, acquiring all that information all the time. It's kind of like a deep learning system. And it's kind of a pop psychology kind of thing now, but our brain is a deep learning system that is accumulating information constantly. And that's what allows us to that low level, under the surface kind of information, is what allows us to know that this is me that's here, I don't have to say that I just know it because it feels right, because I've accumulated all this stuff about what it feels like to be me. And that's true, probably of every animal that there's a kind of certainly, I mean, I think that that that core information has to be represented in a certain way in order to be experienced by the animal. But even if you can't experience it, you can have that kind of deep learning that is providing a kind of extensive coordination of what we could call a global organism estate in an organism that coordinates all of its activities or contributes to the coordination of those activities, and makes it an organism that allows it to be a unit that can do things all at once.

Nick Jikomes 24:07

Yeah, I'd like to talk about this idea of an organism as a unit. When we think about multicellular organisms, right? We've we're thinking about an organism with many different individual cells, many different kinds of cells that do different kinds of things. And you wrote early on in the book that as animals became more complex, and started consisting of multiple cell types organized into systems, new challenges were phased in maintaining the integrity of the organism as a self sustaining unit in which the parts sacrifice their individuality to maintain the physiological viability of the whole and you said that the nervous system is the solution to this kind of problem. So can you sort of expand on that sort of game theoretic idea of different cell types having on the one hand, some kind of individual self interest, but then having to sacrifice that for the sake of the whole unit?

Joseph LeDoux 24:57

Yeah, so the the worst Think about this as to go back to single cell protozoa. These organisms can form colonies. So each individual protozoa isn't a unit on its own, it will survive just fine on its own. But one of the things that happened when the protozoa arrived about 2 billion years ago in response to that, as a kind of, they evolved out of bacteria and other kinds of what's called prokaryotes. protozoa are eukaryotes. And one of the things that happen is they unlike the bacteria and other prokaryotes, eukaryotes are able to grow a little bigger, because of their, the fundamental way biological mechanisms that that constituted their nervous system. And their the fact that they had a nucleus that was contained within a membrane, and organelles in the body, such as mitochondria, they were able to grow bodies slightly bigger than bacteria, bacteria have a fundamental limit, they can never get very big. But eukaryotic single cells got a little bigger, not by me not twice or three times as big, but just big enough, that they could then become predators to bacteria, and then predators to themselves. So there were two other protozoa. So protozoa, the DMF, protozoa, but protest, in general, the, the group that the protozoa belong to, were the first predators. And this means that if you are a little smaller than some of the other organisms, it pays to kind of bind bound to get bind yourself together with other ones, to to get safety in numbers. So if you make yourself bigger, as a group that protects you from single cell organisms that are bigger than you as an individual coming to attacking. And so in these groups, these are all these are all, for example, cells that come from different parental lineages that by the way, protozoa produce invented sex, that's the the first organisms that had sexual reproduction. So we can say that the mother cell of all the cells in the colony isn't necessarily the same. Often, the mother cells are different in the so called daughter cells are collected together just because they're round, and they can fuse together. And so when they do that, through gene interactions amongst the cells that are cleaning together, what you find is that you get these temporary, or these inhibitory effects of all these cells together in their genes, where you get gene suppression, in, in some cells for some functions, remember, each cell can do everything, feed, reproduce, locomote, so forth. But in a colony, each cell gets a job, that's just randomly determined by the kind of algorithm that the genetic probe consequent the protein consequences of the genes are spewing out and causing, you know, the suppression of some genes and the leaving of others alone. So you get some that are going to be involved in locomotion, some we're going to be involved in feeding, so I'm going to be involved in fluid extraction, some are gonna be involved in reproduction. And when that happens, you get a kind of an efficient thing that is very close to being a true organism. But if one of those cells defects and decides to doesn't say, but just for whatever reason, maybe gets bumped out or something. But if it is out in the water alone, it can, it has all of those capacities, because the suppressing genes are gone. And it just reverts back to having everything. But what happened with multicellular organisms is that a way was figured out evolutionarily to have those organisms all come from one mother, one parent cell, and have the same genome. And the when you do that, you can now start from a single cell, a fertilized egg, and create the entire body. How that happens is very complicated. I'm not a biologist, I'm not gonna go into the details. But that's the key thing that in a colony. Each cell has the ability to do everything, but some of the functions are inhibited. But then a real multicellular organism itself only has its primary functions, right.

So it's, the way that started was by a special kind of colony called a clonal colony. In other words, each cell was kind of a clone of the other and so they had all the same genes. And those clonal colonies were responsible for or the evolution of plants, funghi. And animals, the three multicellular kingdoms of life. Because of, you know, once you had these clonal colonies, that was enough for evolution to take over and to figure out a way to put all of that into one cell that within create all the parts that did all the different functions

Nick Jikomes 30:25

I see so So a key, a key step in the evolution of multi cellularity must have involved what you needed to have this one cell that gave rise to many. But in order for all of that coordination to happen, and that specialization to happen, a there has to be a way for the cells to literally stick together. And be there needs to be some kind of communication between them so that one can learn that, oh, I need to turn on this set of genes, but not that set of genes and then start to get specialization,

Joseph LeDoux 30:51

right? Yeah. Now. Something you said triggered something, I forget exactly what it was. But it was a word. Maybe we'll come back to it. Let's go on.

Nick Jikomes 31:03

Yeah, so So when we start, you know, when we start thinking about these early nervous systems, we think about, you mentioned the sponges and the Nigerians, the Nigerians, like jellyfish have this very simple neural net, they don't have a centralized brain, like, like animals do. And the sponges don't have a nervous system, either because they never had one, or maybe they lost it. But one thing that I found interesting to learn about and think about was, they nonetheless, have many of the genes required to make a simple nervous system. And so when we think about organisms that have genes that they don't use for some of these other purposes, or they don't use at the particular time in their development, what does that start to tell us about how we think about how evolution has actually piecing these novel structures together?

Joseph LeDoux 31:47

Yeah, but I think we have to come at it from the different from a different angle, because it's not that evolution isn't using these neural possibilities, the neural possibilities didn't exist. Alright, so let me tell the story of why why I wrote the book if that's okay. Okay. So I've been working on Pavlovian conditioning in the mammal brain for quite some time, number of years, 20 years or so maybe longer. And I, I found out a lot about the neural circuitry involved in the amygdala and other parts of the brain that connect the stimulus to the response and so forth. And then I turned to the molecular mechanisms that might underlie this kind of plasticity. And it's very hard to like, from scratch, figure out how to study molecules in the mammalian brain, or at least it was at that point. But the invertebrate research by Eric Kandel and others had shown all these molecules that were involved, so we decided to just follow their lead and start studying the same molecules. I mean, this was being done in the hippocampus as well for like long term potentiation and plasticity there. So it wasn't I didn't invent this idea. But the field was like moving in this direction. Let's use the hands from the invertebrates. And so it was cool that they okay, we can take something from an invertebrate study done a vertebrate, and show that it's not only involved in synaptic plasticity induced artificially by long term potentiation, which is a kind of, you know, stimulation method. But also, the same molecules and genes were involved in actual learning by the AMA, Pavlovian conditioning. So I didn't think I thought that was just very convenient. Methodologically. But then I spent some time with Seth Grant, who had been a postdoc with Eric Kandel. But at the time, we were doing a sabbatical at Cambridge, which were where Seth was at the time. And we were talking about this a lot. And what came to me from his from his work was that these same some of the same change, let's take NMDA receptors, which are so important synaptic plasticity in mammals. And look at where the, how far back in evolution, those go. So, you know, what Seth found was, okay, you've got it, you've got certain components of the receptor in mammals, you've got the same components in vertebrates, other vertebrates, but you also have them in non vertebrate organisms, invertebrates Of course, like the Candell organisms, please and so forth, and worms and flies and bugs, but also in the jellyfish. Okay, so, okay, they all have nervous systems. So maybe there's something that but also in sponges, sponges don't have a nervous system, what are they doing with components of the NMDA receptor, which is so important for plasticity? Well, maybe that's the wrong way to talk about the NMDA receptor, because you have something in evolution that's there for some purpose in sponges, and in the protozoa ancestors of sponges within these NMDA receptor components. That's there for some purpose, but Now you're going to evolve, you're starting to evolve bodies that get more complex and you get some cells that interconnect locally and then they start growing and then you get a kind of diffuse nervous system and then you have a centralized number system, all this starts from some kind of thing that exists in the non animal organisms non sorry, the non the non animal protozoa. So they, you know, you got the same receptor components and in trees and other plants, and so forth. So, there's something in back there and evolution that these components were used for. But now, when you're moving towards trying to make behavior more complicated, because, you know, the environment is changing, you have predators, and so forth, you got to respond in a new way, along comes the ability to use whatever was in these

other organisms in a new way. And that's what happens, evolution takes what exists and builds up. So I think, yeah, so I wonder, go back to what you said earlier that it couldn't remember them, but you said they kind of stick together. And that's really important, because the reason those colonies stick together, is because they have the cell adhesion molecules, now that the cell adhesion molecules continue to be used, when you go from single cell to multi cell organisms. As part of the mechanism of structural plasticity, in the nervous system, the neurons have, the synapse has to clean together the front and the back of the synapse, the pre and the post synaptic neuron has to clean together. And so these cell adhesion molecules are allowing those synapses to maintain to stay close together, and ultimately initiate growth processes that allowed them to be stabilized. So you know, all this stuff comes from somewhere, it doesn't get invented out of whole cloth. It's all modifications of stuff that existed way back in many ways, in many cases.

Nick Jikomes 37:06

Yeah, so most of the components of the things in the nervous system that we typically associated with, with nervous system stuff and brain stuff, have usually have deep histories where they were used for some other purpose, and they get kind of CO opted and read exactly. For new uses. Yeah, and

Joseph LeDoux 37:22

a great example is the action potential. You know, we think that that is the brain's like signaling mechanism. But the heart has action potentials, too. It's not just the brain, the action potentials all over the place. And where did that come from? Well, it's believed that like this electrical signaling cells is believed to have occurred, way back in evolution as a way of close, you have a single cell organism, there's some damage to the cell wall. So that cell is going to die very soon, because it will leak everything out. But evolution, Mother Nature, whoever we're going to attribute this to figured out that if you create an electrical spark by certain kinds of chemical interactions, that will seal up the cell membrane. And so that electrical spark of protecting the integrity or restoring the integrity of an injured cell membrane, became the basis for electrical signaling in single cell organisms internally for other purposes, you know, communication, and for action potentials when nervous systems came along.

Nick Jikomes 38:33

So when we start to think about the central nervous systems, animals with brains like vertebrates, you often hear in, in sort of pop SCI speak, this notion of the brain as containing like two or three different parts. So you often hear people refer to the mammalian brain as having sort of a reptilian brain and inner core that's responsible for basic reflexes and our baser instincts. And then there's this outer layer with the cortex and the expanded neocortex in mammals and primates that's responsible for thinking and cognition and the mind as we normally think about it. Is that a legitimate way to think about the brain? Or is that confused in some important way?

Joseph LeDoux 39:17

Well, first, you got something, right, that is not right, in a lot of the pop psychology stuff, which is that this is all part of the forebrain, the mammalian forebrain not three levels of the brain in general. I think you got that right. So the, you know, the reptilian brain, people think of that as like the lowest part of the brain, but it's not the lowest part of the forebrain. And then the so you know, in the in the, this all comes from a German neuroanatomist at the turn of the century 20 Turn of the 20th century. Don't name internet. bigwig. Forget US law. theory. But he proposed that the that we have these three brains. And this was picked up on poem by Paul Maclean. Let me just start that I'm going to drop Ludwig out and just say, so all this three brain stuff in modern times comes from Paul MacLean, a neuroscientist, who was at the National Institute of Mental Health and the Washington area in the 1940s, and 50s. And during World War Two, there'd been a lot of research on emotion before World War Two, but during World War Two, the whole research and uprise shutdown, then after world war two things kind of like got rolling again. And that's when Paul Maclean stepped in. And he was looking back at the history of emotion research. And this led him to conclude that in a mammal, early mammals were nocturnal creatures. Based living their lives based on smell, that's correct. And that their brains were wired for this kind of primitive, early response to survival. So the idea was that the mammalian brain, sorry, I'm messing all this up in the startup, so after World War Two, Paul Maclean tried to integrate what had been started in terms of emotion research, before the war, and come up with a new explanation.

And it's so after World War Two, Paul Maclean tried to look back at the research that had been done on emotions earlier. And he came up with a system that had been that was based on the earlier work of editor in the early 20th century, and editor had come up with this idea of three kinds of brains stacked on top of each other kind of reptilian brain that controls instinctual behaviors, a mammalian brain that controls emotions, and a higher brain and the primate or human brain that has thoughts and controls behavior in a rational kind of way. And the claim picked up on this and turn this into a triune brain theory. And the triune brain theory proposed these three levels stacked on top of each other, with the body in the paper, the triune brain paper, I guess, it was one of the Yeah, that just tried to ingrain book, he said that the top part of this three layer thing is the pinnacle of evolution that we've reached the cloud with the peak of of progress with our great cerebral cortex. And, of course, that has been highly, highly challenged and discredited in modern research, because the key to this was that we had a reptilian brain, a brain of that was like reptiles that started at was the earliest mammalian brain. That was then added to, on and on. But research in the 1970s showed that the even reptiles have remnants of cortex. And the I'm really kind of blowing this whole. I'm sorry. Keep going. I'm following you. The images can pause for a second gather my thoughts. Yeah, go for it.

Alright, so in this triune brain, the reptilian brain was supposed to be taken care of instinctual behaviors. And this was supposedly something that was directly passed on from the reptiles. And you ended up with the basal ganglia. As a result, so in reptiles, the basal ganglia was set to to occupy the entire forebrain. And in mammals, it only occupied a small part. But in mammals, we also got something called a NEO basal ganglia or Neo striatum that was supposed to be brand new. Now, it turns out that that Neo striatum, based on modern neuroanatomy actually exist in reptiles. Now, Maclean also said that the mammalian brain, what he called the limbic system, was a new mammalian addition. So just as the, the it's just as mammals got a new reptilian part of the brain are added a part to the reptilian brain, the Neo striatum, the the mammals added a limbic system. And that allowed you to have not only fixed action patterns or instincts, but also now emotions. And because of this mammalian limbic system, and then on top of that, but Well, it's so the mammalian specialty. So the mammalian specialty, the limbic system was supposed to not be in reptiles, but areas of the mammalian limbic system, the amygdala, the hippocampus, others, other areas like that had been found in reptiles, and they've been found inverted lower vertebrates, fish, early fish. So the point is, well, then let's go into the cortex. So the third part, the neocortex, is supposed to only be in and primates but it's present in in rats, but it's also present in birds and reptiles, it's also present in for lower fish. So nothing is really new, it's all modifications, there aren't things that were stacked on top of each other, would happen, this structures became entwined and evolved. This part of the basal ganglia expanded to have a novel part is part of the middle part, what he called the limbic system expanded, so that the amygdala got bigger and more connected. But it was always there even in early fish. And the cortex, also remnants of cart of cerebral cortex neocortex, in in reptiles, just cortex Pallium in fish. So everything as was there from the beginning of the vertebrate brain, it's just a matter of degree. And as you know, as it changed, it evolved and became bigger, and it looked like you know, there were some like major significant changes, but it's all based on something that was already there.

Nick Jikomes 47:10

And you mentioned how everything is so intertwined. And I'm wondering if you could speak a little bit about the difference between emotion and cognition. Because what you know, people often talk about those things as if they're completely separate. One part of the brain is doing emotion, and basic feelings and basic instincts, and other parts of the brain are doing cognition. But to what extent are these things intertwined and inseparable?

Joseph LeDoux 47:31

Well, let's start with a definition of cognition. And I'm giving you my definition, which not everyone will accept, but this is the framework from which I'm working. And you're talking to me, so I'll tell you what my framework is. So I think of cognition, as the ability to create internal representations of the world, and use those representations, when the stimulus in the world that was responsible for those reputations is not present. So it's the ability to draw upon memory, to construct a model of the world in which you can examine different possibilities of action, or different possible ways of thinking, without having to test it out. So if you are a, if you are an animal that only has the ability to undergo trial and error learning, you're going to have to try that trial and error is gonna have to occur in the world. And if it's a dangerous situation, you're gonna have to risk your life to learn what's safe and what's not. But if you are a more complex animal that has the ability to create these mental models, then you can simulate the trial and error, you know, a quick flash decide what to do on the basis of what's going to happen if I do this, what's happened that not literally talking about it like that, but you know, the mental models are able to use that information and, and respond to the world in a more advanced way than you can with just trial and error learning. Now, in the human brain, we can do this, like, literally in a flash of a second evaluate options. Because the human brain is able to simultaneously think of alternatives while working on a problem. other primates seem to have to stop working on the problem in order to consider alternatives. And then they can go back to the problem if the alternatives aren't better, but if one is better than they can go, whereas other mammals have to, even if they have some kind of ability to create mental models, which they do. I've got to just stop this doing. other mammals have the ability to create mental models, but they don't have the ability to pause and evaluate. If they go to two If they go to testing mental models, mentally, they don't go back to the same solution, you have to choose one of those, at least, that's my understanding of the literature on that. So what we see, you know, in a sense, I'm kind of saying like McLean, where we read some pentacle, now we haven't reached a pinnacle, we are a branch of another branch on a twig of a twig, somewhere way out there and on the tree of life. And we're not necessarily, you know, the most recent or certainly not the best, we we've done a lot of good stuff with our cognition and our consciousness. But we've also kind of screwed up the world quite a bit as well for ourselves and others. So I'm not saying that just because we have these abilities that other mammals don't have, that we are better than them, we're just different. We like our differences, because they're ours. But they're just differences. And again, they haven't necessarily always been good differences. But anyway, so we were,

Nick Jikomes 50:58

well, so if cognition has the ability to represent things in the absence of the stimulus being there, right, so I can I can look at something and perceive it in real time, I can also close my eyes and continue imagining it. That's more or less what we mean when we when we say cognition in your framework, when is emotion, how do you think about what emotion actually is?

Joseph LeDoux 51:16

Okay? So, you know, emotion, the typical view of emotions is that you have these basic emotions that we've inherited from other animals. And then we have these more higher order secondary emotions, empathy, and jealousy, and so forth, that weren't necessarily inherited from other animals, but a kind of human social constructions and so forth. And for a long time, my work was used to, and still is used to support this basic emotions idea, so that the amygdala is detecting danger and responding to danger. And therefore is the kind of what the basic emotions there I would call a kind of what do they call it like an athletic program, this system that that is sensitive to certain environmental stimuli and response. But there are two kinds of basic emotions theories. One is about the responses. A lot of the kind of Ekman work is about facial expressions, Paul Ekman about facial expressions, innate responses to so called innate responses to specific kinds of key stimuli in the environment, about danger, and, you know, other other things, anger and so forth. But the the other kind of basic emotions theory is that these athletic programs are also responsible for our subjective conscious experiences. And that is where the amygdala fear center idea comes in. I was, you know, I had always talked about my work, I tried to talk about my work, in terms of the amygdala being an unconscious detector of danger. I came at this from cognitive science, rather than neurobiology. And I was a newcomer to the field. So I adopted the language of the field, I was borrowing the procedure of Pavlovian fear conditioning. And so I called it fear conditioning. But what I tried to do is borrow a terminology from memory. To say that, well, it's, it's implicit fear conditioning, just as we have implicit memory and explicit memory implicit being unconscious, explicit being conscious. The amygdala is involved in implicit or implicit fear, and the hippocampus and prefrontal cortex more an explicit fear, especially in the prefrontal cortex. That the, the idea was that the conscious experience of fear in us and perhaps other animals, some other animals, is the cognitive interpretation of a situation in which we find ourself a mental model of a situation. And where did I get this idea? Well, it started when I was a graduate student working with Mike cassava in the 1970s. So Mike and I were studying split brain patients, these are people on whom the two hemispheres, the connections between the two hemispheres have been split section to help control the spread of seizures from one side of the brain to the other and control because these these people are had very severe epilepsy that wasn't being helped by medications. So then this was a very, obviously a very serious decision for our family to make to choose to do this. But they felt desperate and there were no other options at the time because this was 40 5060 years ago, 50 years ago, and the medications were not working for everyone. How well they work today. I kind of not out of that field now. But the they were fascinating patients because the classic ideas are finding a set in the left hemisphere of a split brain patient, you have language so the person can talk about what the left hemisphere can talk about what it sees and what it added thinks and so forth, whereas the right hemisphere doesn't have language, so it can only respond to the world. So in terms of the so the right hemisphere doesn't have language. So it can't answer questions, but it can respond to the world. So you know that it's alive and responsive. But you just don't know what's in there. But there was a patient in in the group of people that we were studying this, this was a new group of patients that were being operated on at Dartmouth, the other patients had been operated on in California, where Michael was studying them as a student himself. But in the Dartmouth group, we had this one patient who could read in both hemispheres, but still could only talk in the left than the left. So this seemed to be the opportunity to really ask the question,

could you have two conscious minds, one in each hemisphere. So Mike had written a paper called one brain two months kind of speculating about that. But with the right hemisphere, being unable to talk and communicate with you in a kind of meaningful way, it can just point to things and so forth. It was really hard to say that there was anyone home. I mean, there was someone home and something was home, the sense of being behaviorally responsive. But you know, every animal alive is paired with responsive. So we said, Well, let's look at what what we can do with the ability of the right hemisphere to read. So we've put some words into the left visual field, that visual field means it goes to the right hemisphere. But you have to make sure the guy's staring@a.on The screen, so he doesn't move his eyes. Otherwise, it would go to both hemispheres. So, the right hemisphere, we put Who are you, and we placed a bunch of Scrabble letters on the table in front of and left hand, right hemisphere controls, the left hand, pulls out, Pa UL spells his name, okay, this is definitely someone home there because he knows his name. And what's the hallmark of consciousness, the ability to anticipate the future, they anticipate your own personal future. So we asked him, you know, what do you want to be when you grow up, grow up, and he spelled out racecar driver. And we from a conversation with the left hemisphere, it always said he wanted to be a draftsman architect. So here we have two sides of the brain with the same name, but different life ambitions. So it was kind of a fascinating thing. Now is that, you know, did that, did we really nail down the problem there? I don't know. I mean, these are just observations, you got one patient, and you go as far as you can with it. But it was the basis for my and Mike's kind of future careers in a way because Mike went on to develop the idea of the left hemisphere interpreter, as being the left hemisphere interpreter is the the basis of human consciousness. But let me backtrack for a second and say what had happened. So after we observed this patient, that day, we would, after the day's work, we'd go to the bar at night and talk about what we had found. And we were talking about this guy, Paul, and how he, when when we did an experiment, that I haven't mentioned yet that we would present a stimulus to the right hemisphere, that would cause him to perform a response to like, stand up or scratch, or something like that. Are wave. Yeah. So when we did when we get them to get the right hemisphere to do those things, we'd ask the left hemisphere. Why did you do that? And without batting an eye flight, you know, without missing a beat just instantaneously. When we when we said does stand up, and the right hemisphere stood up? We said, Why do you do those said, I had to stretch I was really tired sitting here. When the right hemisphere goes left hand scratching the right hand. Why do you do that? Well had a niche. Why do you laugh? You guys are funny. Yes, it was just like, narrating the story based on his behavior. And so at the bar that I would say, you know, maybe that's what we do. I think it probably might say that I was just, you know, a very young, naive student at two degrees in marketing and Jordan MiCollab. Because that was wild about what he was doing. And he took me anyway, so we said maybe that's what we do all the time. We just, you know, confabulating generating narratives to explain why we do and what we why we do what we do and what we do. Mike was a good friend at the time, with Stanley Schachter, a social psychologist at Columbia. And with Leon Festinger and other social psychologist at the new school up the street in New York, and he As from these two guys from from the passenger, he got the idea of cognitive dissonance. And this is a very popular idea in psychology, right? That when you do something that doesn't sit right, you have to justify it in some way. So when, you know, we all believe we have freewill, right. So we if our, if our body is producing a response, behaving in a way that our brain our conscious brain didn't produce. That's disturbing, because why did I do that? I have free will nuts. What are some what's going on? Why am I doing? Well, Paul showed us that what we do is we just kind of explained it away, needed to stretch. Why did you cheat on your wife? Well, you know, she wasn't that nice to why'd you eat that dessert, you're gonna get fat? Well, you know, one time won't matter. You know, we narrate these stories to ourselves. And also at the bar, we, Mike said, you know, there's not much research on emotion. And you know, maybe those are the kinds of processes that are going to be generating these behaviors, unconsciously, that the that we have to explain to ourselves and others. And faster. Yeah, I'm pretty interested in emotion. And so that's I decided, well, I'm going to turn my work, you know, when you leave split brain research that your mentor is sponsoring, you don't have another group of patients, you're going to be able to study, because there's so few of these, so I had to find something else. So I decided to turn to rats, to study how rats might unconsciously control behavioral and physiological responses to danger.

Because we've inherited the same circuits that control behavioral and physiological responses to danger from animals like rats, not necessarily rats with other animals that are in our direct paths. So I turned to rodent studies of Pavlovian fear conditioning. And because I was a newcomer, I just called it fear. Even though my idea was that emotions, which we got from Stanley Schachter, the other guy that I mentioned up there, who is also a friend of passengers, she actors theory was that emotions are cognitive interpretations of situations. I won't go into the details of his experiments, but he had some evidence for that. And so we bought these two kinds of social psychology concepts and brought them into our interpretations of what was going on. And so I decided that the way I want to think about this is that these emotions that we often will associate with these hardwired responses are not necessarily hardwired responses, emotions, or cognitive interpretations of situations. I've said that throughout my career, I can't say I never said that. The amygdala is a fear center probably did. And you can find it somewhere. But don't blame me for that. Because as John Lennon said, What is Africa? Nothing too good. As John Lennon said, nothing to get hung about, you know, we all make mistakes. And this is talking about smoking cigarettes and strawberry fields or something like that. So anyway, so my view all along has been that emotions or cognitive interpretations of situations, but I'd get introduced at lectures, as someone who had discovered how the amygdala underlies our feelings of fear. I really never, didn't never, I never really accepted. I never really bought that idea. But when I was new to the field, I didn't care. I was young and just doing research and just kind of collecting data. But after a while, in 2012, I had been doing this for 15 years or so, maybe longer. There was like this itch that I needed to scratch and because it was just bugging me that I would be introduced this way, because it's not what I thought, and I had decided I had to do something about it. So I wrote a paper, published it in neuron called rethinking the emotional brain emotional brain was my first book. And so I'm now I'm I said, Now I'm rethinking all this stuff that was in there, even though I talked about emotions as cognitive processes there. There were other things I needed to like, I wanted to just rethink the whole process of how emotions come out of the brain, because the emotional brain was responsible for a lot of the pop psychology that came to underlie the amygdala and so forth. So I just decided to call these circuits like the amygdala circuit, not fear circuits, but defensive response, defensive survival circuits. And the idea that I had was these go back far in evolution, you know, certainly all vertebrates have these defensive survival circuits. Other animals that are non vertebrates don't have an amygdala but they have their own survival circuits, flies for example, we're freeze today during the work of David Anderson. at Caltech, so flies freeze, but they don't have an amygdala, but they have their own kind of circuit that takes the stimulus and connects it to the freezing behavior. But what about animals that don't have nervous systems like that down? And what about organisms that don't have nervous systems, protozoa and bacteria and so forth? Well, they also have to detect and respond to danger, but not with the nervous system. They use whatever mechanisms they have to for their cell walls to detect nutrients and detect toxins, and respond appropriately withdraw or proceed. And so that's why I say danger is as old as life. And, you know, it's often said, starting with Darwin, and on into the basic emotions, there's that fear and other basic emotions or universal and spread around the world. But I think that's wrong, what's universal is danger. Every culture has some kind of danger, you know, it's it's a every organism is, is exposed to danger.

And so every culture has a word for danger. And we can we can translate those words into English word, like fear, very easily. So because we can translate fear across cultures into the same thing, we've seen that the same experiences occur, right? But we know that emotions differ culturally, that different cultures have same words, but the experience of the emotion in different cultures is different. So in the case of fear, it's danger. That is universal, not fear. And the same, I think that's true of all so called basic emotions. It's not the subjective experience, it's the same, it's the eliciting conditions of life that are the same.

Nick Jikomes 1:06:56

I see. So So putting some of these things together. You know, if we think about conscious, consciously experienced emotion as a kind of interpretation, a cognitive thing that's happening after some, some stimulus elicits a response, right? So you see something that we call a fearful stimulus or some kind of danger, you know, your pupils dilate your blood, your blood pressure, and your heart rate change, and so on, and so forth. The emotional experience we have, if I'm hearing you, right, is some kind of cognitive interpretation of those physiological changes that happens after the fact. And it's sort of evocative of what you were talking about, in those classic split brain patients, where you ask them why they did something, and they just confabulate a story, the narrative part of the brain, whatever that is, it's just making something up after the fact. And sort of interesting that's happening after the fact. And so I'm wondering, you know, if, if this part of what the brain is doing this, this emotion thing, this cognitive act, this cognitive interpretation of physiological changes, is happening after the fact it's not strictly necessary for the a lot of the behavioral response. It's not strictly necessary for all of that. So how do you start to think about the adaptive purpose of conscious emotions? What what adaptive value in evolutionary terms did being able to tell those stories actually grant us?

Joseph LeDoux 1:08:13

Thanks for asking that, I think it's a really important question. So in terms of the separation of the responses, let's take a rat that's responding to a tone that's been paired of the shock. So early on in my career, I showed that the inputs to the amygdala that underlie that kind of response are come from the auditory thalamus rather than the auditory cortex. So you can activate the amygdala directly from the thalamus, which is, you know, the station before the cortex and start responding. And what I said at the time was, you know, we've, we react to danger before we know what we're reacting to before, we're afraid. So fear is, this is a slower cognitive process. And, you know, in a sense that it's, it's only natural that it would be slower, because it's a, you know, the energy, the brain energy required to build up to create a mental model of a situation. And to narrate it into spin off the conscious experience, is going to quite be quite energy demanding. So you're not going to do that all the time. If you can do that with unconscious processes, or non conscious cognitive processes, or completely unconscious processes that are automatically elicited like freezing. That's the best thing to do. That means let evolution do the talking for you, or do the thinking for you at first, and then you know, you because and that you can't help but do that because they just come out so fast these automatic responses. So when that's coming out, you then see what's happening. And you began to respond to that. So your behavior again becomes part of the cognitive mental model that you're assembling, but not the only part because the mental model is a assembled. In large part, I would say on the basis of schema. These are men memory structures about specific kinds of things and situations that had been built over the course of your life. You know, Piaget talked about this, and Frederick Bartlett talked about schema in the 1920s, and 30s. And so schema are these, you know, just bundles of memories about kinds of situations. So when you're at work, you call on that work schema, when you're at a party, you call on a party scheme, because you act differently than you do at work and party, you don't have to think about the schema, activate the schema, create the mental part, and, and also the scripts, the the kind of behavioral outputs that you are most likely to be expressing in a situation like that. So anyway, so you got the schema that are building up the model of the situation, these come into the prefrontal cortex, by way of the hippocampus and into the ventromedial prefrontal cortex. And where the schema our hippocampus and medial ventral medial are, are communicating as the situation changes, and so the schema will change. But the ventromedial outputs go to the lateral prefrontal cortex where the cognitive mental model is being assembled. And within that model, is not only the schema, but also specific stimulus information, other kinds of memories, body feedback, your goals and aspirations, your hopes and dreams, all of that comes into the mental model. And then, and then the output of the mental model. And this is in my so called model of how this works, is the narrative. So a narrative in this sense, is a kind of abstract, it's not a it's not language, it's an abstract code that comes out of the mental model, and controls behavior,

including speech, and also populates a conscious mental model. And the conscious mental model then can also control behavior and speech, but separately from the unconscious one. So the why well, that's the purpose of consciousness is not just to have the experience, but that it's adaptive, it opens up another level of decision making for you that you don't have if you stick strictly responding unconsciously, an unconscious mental model is good. And again, it's it's less energy demanding than a conscious one. So that's your kind of go to process. But in the process, that the unconscious process of going through that something triggers, something is triggered, that doesn't feel quite right. That's what will signal the generation of the conscious mental model. So earlier, we talked about this kind of deep learning in the brain that is kind of just always accumulating information, and allowing you to know that it's your body and your mind that's involved. So the idea is that the one of the things that would be important in the triggering of the conscious mental model is that so called what psychologists called the feeling of rightness, William James kind of started, they started everything, but the feeling of rightness that occurs when everything is right. But when something is a little off, you get this, you know, violation of that rightness. And that triggers something else. And that triggering is the what justifies the use of the energetic required to make the conscious mental model. And so what's interesting is, how all of this works in the human brain. Because I think, if we knew more about how it works in the human brain, what are the areas and interactions between areas involved in human consciousness, we would be able to speculate, given what we know about what our brain is doing, what other brains what the brains of other animals might do, given the similarities and differences with our brain. And so, I use I like the partition of consciousness that Endel Tulving created some time ago, which is between auto noetic or self reflective consciousness evolving and many others made this perhaps a kind of yet human, or at least, you know, human, chimpanzee kind of ape, kind of, we are apes, so we can call it kind of an ape consciousness that is able to internally represent oneself as the agent. I mean, we don't we can't prove that he had this, but they seem to have all of them to have enough of the kind of stuff we have that they probably have something like that. So the self reflective consciousness would be limited in evolution where As noetic consciousness is knowledge of facts and semantic knowledge of facts and concepts, so you have a conceptual representation of the world that is very, you know, elaborate if you're a monkey, but you may not be able to take that next step that requires the reflective self that leads to the reflective self awareness. Because your brain is whilst quite similar to ours, it's not the same. And what about other mammals? Well, the third kind of consciousness is no at a notice the third kind of consciousness is a noetic consciousness. Now, this was puzzling to me for a long time because Tulving called this non knowing awareness, based on non knowing knowledge, what the hell does that. And, you know, I thought, this, I can't buy this, because, you know, it's unconscious conscious. And the psychologists neuroscientists, Jacque Panksepp used to talk about this kind of unconscious consciousness as well. And Yaak and I had a lot of disagreements about. We frequently we're just in disarray in, we're frequently we're not in agreement about consciousness and emotions.

But I figured out that it's all about one thing, that our disagreement was totally about a noetic consciousness. Because, as he said, and that, I believe, now that that's what rats and other Matt lower mammals have called lower, but non primate mammals have, is this a noetic consciousness, this ability to know that this is my body, these are my mental states. But without any kind of explicit awareness or explicit acknowledgement of that. It's just that it's there. And when it's not there, then you know, something is triggered. Now, Panksepp said that that was all subcortical, limbic stuff that was responsible for that. But I think that it has to be represented cognitively, just as the amygdala has to be represented cognitively, in order to have the fear. So the idea is that we have these, let's say, let's just take the deep learning systems have a rat subcortical brain, that it's, it's acquiring all, let's just say, of the right brain, because it's unconscious stuff throughout the brain. So the deep learning in this rat brain is acquiring information about the environment, what is the normal, you know, I won't say what feels right, but what is normal, typical, and what is not typical. And so even through some kind of, you know, expectation violation mechanism that we hear a lot about in neuroscience, you know, predictive coding and errors and all that stuff, you got to get something that violates an expectation that triggers something. So if all this deep learning stuff is hunky dory, and then all of a sudden something violates the expectation of hunky dory, this, then that triggers something else. And what that triggers is a real representation of that information. And ventromedial prefrontal cortex and other kind of more primitive prefrontal areas like the prelimbic cortex. And a rat, for example, is supposed to be their working memory area, and so forth. So this would allow the animal to now have the kind of higher order representation. But if you're a monkey, instead of a rat, you can take that representation and re represent it cognitively, through their lateral prefrontal cortex, this granular prefrontal cortex that monkeys have with that rats don't have and that gives you a highly conceptualized information about the violation of that goodness, that hunky dory Enos of the deep learning, and if you're a human, you can also put that into a very personal kind of self reflective way that allows you to what Calvin called have mental time travel, the ability to project yourself into the past. Now, John Locke long ago said, How do I know that the me that I am today is the same me I was, you know, when I was young, he said, Well, it's because you have the memory of yourself as young and he didn't know about auto noetic consciousness and self reflection and on the magazine you have self reflection but but tall beings auto noetic consciousness is what that is. It allows you to go to yourself in the past, and to make decisions about who you were in the past, but also to allow you to be in the present, as you and importantly, to visit the future. have a mental model that goes not just to the past, but to the future, where you can explore the opportunities based on what happened in the past based on what you know now, but also based simply on creativity, the ability in the middle model, to use language and to use all of the things we have to explore opportunities for deciding and acting that monkeys and rats simply don't have, because they don't have the kinds of brains we have. So, you know, if we let's just take, I'm going to, say give you an anatomical hypothesis about these three kinds of consciousness. And it's not necessarily meant to be factual in the sense that this is actually how it works. But it's an example of, if it were like this, it would allow us to say it, this is a clear distinction, that allows us to say, if

monkeys and rats don't have this kind of cortex, they probably can't have this kind of consciousness. If rats don't have this kind of cortex, they probably can't have the kind of consciousness that monkeys have, so forth. So this was all talked about an article in Current Biology that I published in 2021, called What emotions might be like in other mammals, other animals. So there's a part of the prefrontal cortex called the frontal pole. And the frontal pole wraps around from the lateral surface to the medial surface. And it's all granular cortex, most of the medial surface is not granted. But the frontal pole is a granular representative representation that goes into the medial prefrontal cortex. But in the lab, and monkeys have that and, and humans have that, but rats don't have it. Now, the lateral frontal pole has a part, a component in the human brain that even monkeys and chimpanzees don't seem to have. So let's say that that lateral frontal pole specialization, well, it's unique molecular, not just anatomical, but molecular and genetic specializations that aren't present in the other animals. Let's say that is, you know, what gives us that extra stuff that underlies our so called, you know, auto noetic consciousness, mental time travel and blah, blah, blah, there is some evidence that, you know, subjective metacognition, the ability to change your mind involves the frontal pole, but it's, it's more medial frontal pole. So it's, but let's just say it's lateral for the sake of this argument, that so because monkeys don't have that, then they can't have what that structure makes for us. And but monkeys do have very well developed sophisticated dorsal lateral prefrontal cortex for working memory. And that is where we create our working memory models. And the working memory circuits and rat in monkeys and humans are quite quite similar. Now, what about other mammals? Well, they have all those medial prefrontal areas that are non granular, and can do all the things that our medial prefrontal areas can do, but in a kind of not so souped up way. So the idea would be that if our medial prefrontal cortex is responsible for a noetic awareness, and our dorsal lateral prefrontal cortex, for noetic, awareness, conceptual and semantic awareness, and our frontal pole for auto noetic, or awareness, then we would be able to speculate about what other animals what other primates have, and what other mammals have that's similar and different to ours. That's the basic idea. And again, it's not that those necessarily are correct. But they're just kind of a model of what if we knew more, this is what we could talk about. So the interesting

Nick Jikomes 1:24:02

one of the things just to try and summarize what you were saying that I found fascinating, was, you know, when you were talking about what we might just call basic awareness, or what seems to be a contradiction in terms like cottoned on conscious awareness that other animals might have. That reminded me a lot of when people talk about things like flow states that we've all probably experienced at some point, right? Where you're having perceptions, you're aware, you're aware of what's going on, but everything just sort of seems to be flowing like one domino after another and you're not sort of engaged in this narrative deliberation that humans are also capable of. And what's interesting about that is a such dates are possible. It's possible to be aware without sort of those narrative, deliberative forms of cognition happening. And people often experience these to be very, you know, pleasurable or peak experiences that that are good to have. Now, on the other hand, based on what you were saying, our ability to re represent things to go beyond the sensory representation itself. can't represent that as a more abstract representation in our minds, that opens the space of possibilities with respect to problem solving. So without that we couldn't solve as many kinds of problems as we can solve as humans. And what's interesting about this, I think, is that this would appear to be sort of a blessing and a curse. This ability to get to go into abstract representations allows us to figure out things we couldn't figure out and that other animals can't. But it would seem to be also just the thing that opens us up to certain forms of mental illness like, like the forms of depression or anxiety we have, which are if you think about it, they are sort of, they're wrapped up in this ability to do mental time travel and get stuck in the past and be depressed about or be anticipating the future in a way that makes us persistently anxious. Is that a reasonable way to think about it?

Joseph LeDoux 1:25:44

Absolutely. You know, Kierkegaard said that anxiety is the price we pay for freedom. And he was talking about Adam choosing, you know, the apple in the Garden of Eden. But what another way to talk about that is the, that the anxiety is the price we pay for having a prefrontal cortex that can anticipate the future and worry about it.

Nick Jikomes 1:26:09

Interesting, interesting. One last thing I would love to ask you about while you're here, and because I'm talking to you, is, is to do with the question of memory. And a couple things are interesting about memory with respect to humans and certain other animals. One, we have very good memories in the sense that we can form many memories that are very durable over very long periods of time. But also, as your work has shown over the years, memory is more labile and plastic than we often recognize as we're going about our day to day lives. And in fact, I think your work has shown that potentially every single time that we recall a memory there is a kind of reconsolidation process that happens. And those memories are not static and fixed and reliable. They're actually changing over time. And so what is the sort of plasticity of, of memory start to tell us about how trustworthy are our thoughts and our narrative structures that

Joseph LeDoux 1:27:05

we tell ourselves actually are young? You know, there's, there's this thing. reconsolidation was something that had been kicking around in the field, and kind of suppressed for a long time since I think probably since the 1960s. And then in 2000, a really bright postdoc in my lab, Kareem Nadir decided that he wanted to, you know, he found out about this, so we got to study this. Now that'll never work. And the idea that we had what we we had just published a paper showing them start over. So reconsolidation work in my lab came out of the work of cream Nadir, a very bright postdoc at the time still vary by person who had looked into some older literature and found that there was there were studies showing that if you lack protein synthesis one more time sort of reconsolidation work in my lab was the work of Kareem Nadir, who was a very, very bright postdoc, and working with me. And he was looking into some older research. We had just done an experiment where we put protein synthesis inhibitors in the amygdala. That's okay, you have to do it one more time. Sorry,

Nick Jikomes 1:28:36

but with time it was 927 Right now,

Joseph LeDoux 1:28:40

okay. Yeah, we can go to like 45. No, no 15. So So reconsolidation in my lab started as a kind of byproduct of our work on consolidation. Consolidation is the process of stabilizing memories after their form. So, one of the classic findings in the field was that if you block protein synthesis, after the formation of a memory, shortly after the formation of a memory after learning, then that memory is not stored in a long term sets. So the idea was that these the proteins that would be made are not there. And those proteins would be involved in the conversion of short term to long term memory but within skews, the idea was that the if the proteins that are involved in the conversion of short term or long term memory are blocked, then long term memory can't be formed. Now, creme Nader, in my lab was interested in in this work that Glenn Schaefer and I had done on consolidation. And he was looking into this and came across this older literature in the 1960s. Since 70s, that showed that not only if you block protein synthesis after learning, do you lose long term memory. But also if you block protein synthesis after the retrieval or the remembering of a memory, block it you prevent long term memory the next time. So, you know, Kareem walked into my my office and said, Joe, I want to I want to study reconsolidation, I said, No, what is that? He explained, I said, That'll never work. So he left, a month later, he comes back said I got it. So what you get is a well, I showed that if we blocked protein synthesis in the amygdala after the retrieval of fear conditioning in rats, and the rats don't freeze anymore to the tone, ah, and they don't freeze the next day, that's like, you need protein synthesis, not just to learn and create a long term memory, but also to restore the memory after it's been taken out. The idea is that, when you take it out, it becomes unstable. And that means you have the opportunity to add new information, good information positive, support the memory, but also to change the memory in ways that aren't necessarily useful, you can like erase the so called erase the memory. Now the whole memory eraser thing kind of got blown up and way out of hand, the whole idea that we could take these findings in rats and transfer them to humans, and we'd be able to cure PTSD with my blocking by preventing this reconsolidation process from taking place, it never really fully panned out. And part of the problem is that we were studying a very simple kind of behavior in rats tone paired with shock. That's one of these, you know, Pavlovian conditioned reactions that don't require any thought or consciousness or anything like that. It's just like automatic. But in PTSD, the whole problem is all the cognitive and the thought processes and the rumination and so there's no way that you can take a complex memories, it's really big and full of all sorts of stuff represent some component that's related to that, and away it's gone. So I think reconsolidation could potentially be used as a way to block some of the behavioral and physiological responses that get conditioned during those steps. But not necessarily to change the memory. I mean, the good news, that is I mean, like, George, President George Bush's bioethics council came down hard on us when we suggested that, you know, we might be able to change human memory by doing this. So we thought about a lot and we kind of concluded well, yeah, it's, it's really a different thing that human memory is a much more complicated thing. And the good news is, we did some experiments, even in rats showing that if you make a more complex memory with lots of conditions, stimuli controlling the behavior, and you extinguish one of them, you don't erase the whole process, you only kind of eliminate one part of it. So the good news was that you might be able to chip away piece by piece at a complicated memory in the human brain. But I think even that is, you know, at this point, has not been clearly demonstrated. So it's still, I think it's still possible that it could be useful, but like a lot of things that look really great and promising at first, it didn't pan out to be as quite as powerful as we had hoped.

Nick Jikomes 1:33:37

Well, I mean, connecting vastness, some of the thoughts we were giving us before about, you know, what a conscious conscious experience emotion is, is that, you know, if the conscious experience of an emotion is some kind of cognitive operation, the kind of story we tell ourselves about the physiological response we have to a stimulus or to a memory with connecting that to this idea of reconsolidation, or the plasticity of memories. You know, the hope was originally with reconsolidation, oh, we can go in and you know, erase the traumatic memory of PTSD. Well, maybe you can't erase it, but you can change the way the person is, is sort of giving themselves a narrative about it. And that, to me, is very evocative of what we see with things like these clinical trials using MDMA for PTSD or you hear the patient's afterwards and their memories not gone. They still remember the traumatic event, but their experience of the remembering of it is now very different in terms of its emotional valence.

Joseph LeDoux 1:34:28

Right? Yeah, I mean, the good news about the cognitive idea of emotions and fear and anxiety and so forth, is that if a lot of it is the cognitive interpretation, that means you can reinterpret that you can reappraise it and perhaps do quite well with that. So I'm really kind of anti drugs and turns of fear and anxiety, for example. So let's talk about how drugs are developed to treat people. Take a rat or a mouse and a drug cop When you put it into Pavlovian conditioning or some other kind of circuit that depends, that is a kind of defensive survival circuit, give the animal the drug that makes him freeze less or avoid less. And you think, Well, okay, because fear is the cause of freezing in humans, then we, if we make rats freeze less by this drug, it ought to make people feel less fear. But what has happened? Well, the whole history of the pharmaceutical industry is kind of reversing the concept. Well, we're throwing our hands up, we can't find anything new that we didn't discover in the 60s, often accidentally. And so but the problem is that the conception of what fear is, I think, has been wrong. It's nothing. There's nothing wrong with the experiments. I mean, if you give the animals and one of those experiments on a drug company and SSRI and it freezes less, he gave it to a person, if they freeze less, that's progress. Right. But, you know, instead, so the party line has been in, in the industry in psychiatry, that this is an anti anxiety drug. Now, let's take whatever anxiety Do you want to talk about, this is the anti anxiety drug, it'll make you less anxious. And you'll go to the party, and you won't, you know, you'll be okay. But what they think what they should have been saying is, well, this is a drug that will affect your physical symptoms, it will make you less jittery and less aroused, and maybe less avoidant, when you're about going to the party. But you're anxious, you're an anxious person, you've been anxious all your life, you probably still be anxious at the party. But you can use the drug to moderate your symptoms, your physical symptoms, and become a little more comfortable being at the party. And if you expose yourself this way, with the drug and onboard, you know, you can perhaps begin to have a social life at parties like this, but not necessarily an anxious free social life. I mean, anxiety is part of life, and we all have it. So there's no fully eliminating it. It's just you have to learn to live with the amount of anxiety that that you have in your experience at these parties.

Nick Jikomes 1:37:22

I see. And so I mean, do you do you feel like do you feel like a lot of our standard anti depression, anti anxiety medications have been used and widely used for reasons that are a bit misguided?

Joseph LeDoux 1:37:36

Well, I think we've, the problem is we've just misunderstood what these things are. I mean, we've we've so marginalize, you know, psychiatry, and behaviorism. And all of that was so anti Freud, that when behavioral therapies came along in the 50s, and drug therapists were coming along in the 50s, the goal was to keep anything subjective out, because that's what Freud was all about. But they threw the baby out with the bathwater, okay, you can get rid of, you know, repression is sexual abuse, repression, blah, blah, blah, and other things that were at the Troy touted that were, you know, more doubtful, but you can't have a psychiatry that ignores the subjective experience of the patient. Now, we just wrote a paper called putting the mental back into mental disorders, it's about how, you know, over the entire course of since the 1950s, subjective experience has not been valued. You know, when I wrote a paper with a colleague on these two systems for fear, like the fear is the cognitive part and the non cognitive, automatic and make the report is separate, that that that subjective experience needs to be part of the therapeutic goal, not just, yeah, and the insurance companies, you know, care about that. Yeah, it's about metrics, get the what can you got 10 or 12 things on a list? If you have three of those, and you have this three got three on another list, you have that? You know, so there are so many ways to have any one thing, that it's it's kind of it's about the the symptoms, it's not about the experience, and if the person is treated, and the the at the end of therapy, they don't feel better than the therapy hasn't been a success. You got to somehow address the the subjective experience. I think every therapist implicitly does that. But it's not part of the, the, you know, the checklist is not part of the not a central part. It should be the number one thing and all that other stuff is supporting and making it harder to have a proper subjective experience. it's comfortable for you. And so we have to kind of reverse that whole decades and decades of the way we think about what these things are.

Nick Jikomes 1:40:09

Well, Joseph Ledoux, I want to thank you for your time. I've always been a big fan of your work. Do you want to mention just one last time for people what what your last book was and leave people with any final thoughts you have?

Joseph LeDoux 1:40:19

Sure. The last book that I published was called the deep history of ourselves the 4 billion year story of how we got conscious brains. And you know, one thing I think that I left out of the discussion earlier, if I could just pop that in as an afterthought when we were talking about a New Relic, noetic and automatic consciousness in humans, as arkpak Jaak Panksepp said, and I totally agree. These automatic states and noetic state, well, I don't know what extent in humans, I don't know where they can noetic states, the explicit states with content overshadow these energetic states that are more subtle, and just kind of there in the background. But in rats, and other lower mammals, non primate mammals, that's all they have is these energetic states. And so that's why he would talk about these kinds of unconscious conscious emotions and rats. But everybody thought he was talking about real fear, our fear, that animal fear and our fear was the same. And that's how the whole problem comes up. But that's not what he was saying. Even though he kind of said that in public, so it's a little confusing. But it's important to remember that no attic is there all the time. If you can have no attic, you have no attic, Na, no attic, but the noetic will overshadow the BA nobody. And if you can have otter, no attic, it will overshadow everything else. But every note every automatic state, every explicit self reflective state includes conceptual and semantic knowledge, factual knowledge about who you are, and all of the stuff you know. And also this a noetic feeling of rightness or wrongness that is there or not there. But those fall into the background of the automatic self reflective experience, that is what you count, that's what counts when you are in a similar situation where it is you that is having the experience.

Nick Jikomes 1:42:21

Yeah, I mean, it reminds me a lot about you know, the the meditation literature. So to use the language that you were using, you know, a lot of the meditation people, meditation practitioners sort of are basically saying that the point of the practice is to let the noetic and auto noetic operations of the brain calm down and wind down. And if you achieve that, then the noetic stuff becomes much more visible because it is so subtle,

Joseph LeDoux 1:42:45

right? You know, I think one of my books, I forget which one, but I said that meditation might be the use of working memory. Usually we use working memory to select information and pull it into working memory, right. But meditation may be used to like select information and shut it out of working memory and allow them those they know any states to rise up and flow as you were talking about.

Nick Jikomes 1:43:13

Well, I think that's a great spot to end it. Professor Joseph Ledoux thank you for your time.

Joseph LeDoux 1:43:17

Thank you and fun

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